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ROTONDO, John Charles. "Mechanism of progression in cervical intraepithelial neoplasia." Doctoral thesis, Università degli studi di Ferrara, 2015. http://hdl.handle.net/11392/2389088.
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The cervical intraepithelial neoplasia (CIN) grade 1, 2 and 3 are the precursor lesions of cervical cancer. Due to the lack of useful study models, the molecular mechanisms involved in CIN progression are still largely unknown.
The overall aim of my study was to investigate the molecular mechanisms occurring in CIN lesion progression. This goal was achieved by investigating gene expression profiles and methylation status of gene promoters in a novel study model of tumor progression, i.e. primary colonies of CIN2 and CIN3 keratinocytes derived from CIN2 and CIN3 lesions. To this purpose, the first aim of my study was to develop a rapid and simple cell culture protocol enables primary colonies of HPV16-CIN2 and HPV16-CIN3 keratinocytes to be derived from small tissue fragments of CIN2 and CIN3 lesions. The primary colonies of CIN2 and CIN3 keratinocytes were then investigated for presence epithelial and cervical markers showing cytokeratin -14, -17, -19 expression. In the second part of my study primary colonies of HPV16-CIN2 and HPV16-CIN3 keratinocytes were chosen to be investigated by microarray analysis. Differentially expressed genes were analyzed in normal cervical keratinocytes compared with HPV16-CIN2 keratinocytes and in HPV16-CIN2 keratinocytes compared with HPV16-CIN3 keratinocytes. Thirty-seven candidate genes with continuously decreasing or increasing expression during CIN progression were identified. Specifically, 23 down-expressed genes involved in antiviral immune response and differentiation and 14 over-expressed genes involved in proliferation and tumor invasiveness were identified. One of these genes, phosphoglycerate dehydrogenase, was chosen for further characterization. Quantitative reverse transcription-polymerase chain reaction and immunohistochemical analysis confirmed that expression of phosphoglycerate dehydrogenase consistently increases during progression of HPV16-CIN toward cancer. Phosphoglycerate dehydrogenase is likely to be associated with tumorigenesis and may be a potential prognostic marker for CIN progression. Finally, in the third part of my study, to verify whether down-expression of genes in CIN2 and CIN3 keratinocytes depended on DNA promoter methylation, I investigated the methylation status of RARB and IRF6 promoter, both tumor suppressor genes, in relationship with expression of their two pathway-correlated genes, p63 and c-JUN. The epigenetic analysis revealed a hypermethylation of RARB and IRF6 gene promoters in CIN2 and CIN3 keratinocytes compared to normal keratinocytes as well as a progressive hypermethylation of RARB promoter region from normal to CIN2 keratinocytes and from CIN2 to CIN3 keratinocytes. Consistently, a gradual up-regulation of p63 and c-JUN from CIN2 to CIN3 keratinocytes was detected. It is conceivable that the hypermethylation of RARB and IRF6 promoter region may cause a consequent RARB and IRF6 down-regulation and this reduction of expression could enhance c-JUN and p63 expression in CIN keratinocytes.
In conclusion, in my study the molecular mechanisms occurring in CIN lesions progression were investigated. In particular, it was investigated gene expression profiles and methylation status of gene promoters in a novel study model, i.e. primary colonies of CIN2 and CIN3 keratinocytes derived from CIN2 and CIN3 lesions. Gene expression analysis revealed 37 down-expressed or over-expressed genes which may contribute to CIN progression. One of these genes, the phosphoglycerate dehydrogenase, which resulted over-expressed at both mRNA and protein level in CIN2 and CIN3 keratinocytes and in CIN2, CIN3 and cancer tissues, respectively, is likely to be associated with tumorigenesis and may be a potential prognostic marker for CIN progression. Aberrant promoter hypermethylation of RARB and IRF6 genes also may be a potential epigenetic prognostic marker for CIN progression.
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Keenan, Stephen J. "Quantitative analyses and classification of cervical intraepithelial neoplasia (CIN) using automated machine vision." Thesis, Queen's University Belfast, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368597.
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Flynn, Sarah E. "SHAME, GUILT, AND KNOWLEDGE OF HPV IN WOMEN RECENTLY DIAGNOSED WITH HPV-RELATED CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN)." UKnowledge, 2010. http://uknowledge.uky.edu/gradschool_diss/10.
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The current study investigated the relationships between state shame, guilt, and disease knowledge in women recently diagnosed with cervical intraepithelial neoplasia (CIN) caused by the human papillomavirus (HPV). Recent research has indicated that diagnosis of HPV can elicit negative self-directed affect, including persistent experiences of shame. Studies have also shown that knowledge of HPV is low in the general population, even though it is the most common sexually transmitted infection. It is important to understand how shame affects those with HPV because shame is related to a decline in important immune parameters that may be essential in HPV clearance. A sample of young women (ages 18-28) recently diagnosed with HPV were given measures of shame and guilt-proneness, state shame and guilt, depression, impact of diagnosis, and HPV knowledge. A comparison group of women diagnosed with infectious mononucleosis caused by the Epstein-Barr Virus (EBV) were also given these measures. It was predicted that women diagnosed with HPV would have higher levels of shame and guilt than women diagnosed with EBV. It was also predicted that disease knowledge would moderate negative affect in women with HPV, where increases in HPV knowledge would neutralize feelings of shame and guilt. The results of this study supported the first hypothesis: women with HPV experienced more shame and guilt than women with EBV. Shame largely mediated the relationship between diagnosis of HPV and depression, as well as HPV and distress, but these relationships were not significant for guilt. The hypothesis that disease knowledge would moderate feelings of shame was not supported in this study. Because of the biological and psychological consequences of shameful experiences, research should continue to measure factors that may predict shame after diagnosis of HPV.
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Nath, Rahul. "An Investigation into the prevalence of abnormal cervical smears and cervical intraepithelial neoplasia (CIN) in women with systemic lupus erythematosus (SLE)." Thesis, King's College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.438963.
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Elfgren, Kristina. "Longitudinal studies of human papillomavirus infection : with special reference to screening for cervical cancer and treatment of CIN /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-673-1/.
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Wang, Y. "Computer assisted diagnesis of cervical intraepithelicel neoplasia (CIN) using histological virtual slides." Thesis, Queen's University Belfast, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.492486.
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This thesis proposes a prototype automated computer-assisted system for the diagnosis of CIN using ultra-large virtual slides (up to 120Kx80K pixels at a resolution of 0.25 !-un/pixel). The system is in two parts: the segmentation of squamous epithelium, and the subsequent diagnosis of CIN. For the segmentation of squamous epithelium, to save processing time, a multiresolution method is developed to segment ultra-large cervical virtual slides. The squamous epithelium layer is first segmented at a low resolution, and the boundaries are further fine tuned at a higher resolution. The block-based segmentation method uses robust texture features in ~ombination with a Support Vector Machine (SVM) to perform classification. Medical histology rules are finally applied to remove misclassifications. In tests using 31 virtual slides the segmentation achieves an average accuracy of more than 94.25%. For the diagnosis of CIN, so-called 'connecting lines', along the direction of possible progression of CIN in the epithelial layer, are firstly identified. Four connecting line features are developed based on morphological characteristics of nuclei. Using multicategory SVM, connecting lines are classified into Normal, CIN I, CIN II, and CIN III. The final diagnosis for a slide region is based on combining the classification of connecting lines in the region.. The robustness of the system in term of regional diagnosis is measured against slides manually classified by two pathologists. Interobserver variability is considered. Results indicate that the system offers a promising basis for a computer-assisted diagnostic tool. It main limitation is seen to be in the selection of more extensive and more varied training data.
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Carrasco, García Miguel Ángel. "Neoplasia Intraepitelial Cervical grado II y III: Estudio morfométrico de sus diferencias y relación con el Virus del Papiloma Humano." Doctoral thesis, Universitat Internacional de Catalunya, 2010. http://hdl.handle.net/10803/9355.
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El propòsit del nostre treball és valorar morfomètricament les diferències existents entre la Neoplàsia Intraepitelial Cervical (CIN) grau 2 i 3, així com el tipus de Virus del Papil·loma Humà (VPH) present, estudiat mitjançant Hibridació in situ.Hem estudiat 66 peces quirúrgiques d'exèresi del coll uterí de pacients amb diagnòstic histològic de CIN 2 i 82 de CIN 3. Hem demostrat amb el nostre estudi que la superfície afectada en el coll cervical per CIN 3 és significativament més gran que la de CIN 2, a la vegada que són lesions longitudinalment majors, amb major afectació glandular, major profunditat en l'afectació glandular i major índex mitòtic. També hem pogut demostrar que VPH 16/18 predomina en CIN 3. No hem trobat diferències significatives en quant a la presència de papil·les vasculars en ambdues lesions i tampoc hem trobat relació entre tipus de VPH i àrea afectada per CIN, així com entre tipus de VPH i edat de la pacient.
El propósito de nuestro trabajo es valorar morfométricamente las diferencias existentes entre la Neoplasia Intraepitelial Cervical (CIN) grado 2 y 3, así como el tipo de Virus del Papiloma Humano (VPH) presente, estudiado mediante Hibridación in Situ.
Hemos estudiado 66 piezas quirúrgicas de exéresis del cuello cervical de pacientes con diagnóstico histológico de CIN 2 y 82 de CIN 3. Hemos demostrado con nuestro estudio que la superficie afectada en el cuello cervical por CIN 3 es significativamente mayor que la de CIN 2, a la vez que son lesiones longitudinalmente mayores, con mayor afectación glandular, mayor profundidad en la afectación glandular y mayor índice mitótico. También hemos podido demostrar que VPH 16/18 predomina en CIN 3. No hemos encontrado diferencias significativas en cuanto a la presencia de papilas vasculares en las dos lesiones y tampoco hemos encontrado relación entre tipo de VPH y área afectada por CIN, así como entre tipo de VPH y edad de la paciente.
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Miranda, Gisele Helena Barboni. "Método para processamento e análise computacinal de imagens histopatológicas visando apoiar o diagnóstico de câncer de colo de útero." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/95/95131/tde-24012012-154506/.
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A histopatologia é considerada um dos recursos diagnósticos mais importantes na prática médica e caracteriza-se pelo estudo das alterações estruturais e morfológicas das células e dos tecidos causadas por doenças. Atualmente, o principal método utilizado no diagnóstico histopatológico de imagens microscópicas, obtidas por meio de amostras em exames convencionais, é a avaliação visual do patologista, a qual se baseia na experiência do mesmo. O uso de técnicas de processamento computacional de imagens possibilita a identificação de elementos estruturais e a determinação de características inerentes, subsidiando o estudo da organização estrutural das células e de suas variações patológicas. A utilização de métodos computacionais no auxílio ao diagnóstico visa diminuir a subjetividade do processo de avaliação e classificação realizado pelo médico. Diferentes características dos tecidos podem ser mapeadas por meio de métricas específicas que poderão ser utilizadas em sistemas de reconhecimento de padrões. Dentro desta perspectiva, o objetivo geral deste trabalho inclui a proposta, a implementação e a avaliação de um método para a identificação e a análise de estruturas histológicas, a ser utilizado para a análise de lesões neoplásicas do colo do útero (NICs) a partir de amostras histopatológicas. Este trabalho foi desenvolvido em colaboração com uma equipe de patologistas, especialistas do domínio. As imagens microscópicas digitalizadas foram adquiridas a partir de lâminas previamente fixadas, contendo amostras de biópsias. Para segmentação dos núcleos celulares, foi implementado um pipeline de operadores morfológicos. Métodos de segmentação baseados em cor também foram testados e comparados à abordagem morfológica. Foi proposta e implementada uma abordagem baseada em camadas para representação do tecido, adotando-se a Triangulação de Delaunay (TD) como modelo de grafo de vizinhança. A TD apresenta algumas propriedades particulares que permitem a extração de métricas específicas. Foram utilizados algoritmos de agrupamento e morfologia de grafos, adotando-se critérios de semelhança e relações de adjacência entre os triângulos da rede, a fim de se obter a fronteira entre as camadas histológicas do tecido epitelial de forma automática. As seguintes métricas foram extraídas dos agrupamentos resultantes: grau médio, entropia e taxa de ocupação dos triângulos da rede. Finalmente, foi projetado um classificador estatístico levando-se em consideração os diferentes agrupamentos que poderiam ser obtidos a partir das imagens de treinamento. Valores de acurácia, sensitividade e especificidade foram utilizadas para avaliação dos resultados obtidos. Foi implementada validação cruzada em todos os experimentos realizados e foi utilizado um total de 116 imagens. Primeiro, foi avaliado a acurácia da metodologia proposta na determinação correta da presença de anomalia no tecido, para isto, todas as imagens que apresentavam NICs foram agrupadas em uma mesma classe. A maior taxa de acurácia obtida neste experimento foi de 88%. Em uma segunda etapa, foram realizadas avaliações entre as seguintes classes: Normal e NIC-I; NIC-I e NIC-II, e, NIC-II e NIC-III, obtendo-se taxas de acurácia máximas de 73%, 77% e 86%, respectivamente. Além disso, foi verificada também, a acurácia na discriminação entre os três tipos de NICs e regiões normais, obtendo-se acurácia de 64%. As taxas de ocupação relativas aos agrupamentos representativos das camadas basais e superficiais, foram os atributos que levaram às maiores taxas de acurácia. Os resultados obtidos permitem verificar a adequação do método proposto na representação e análise do processo de evolução das NICs no tecido epitelial do colo uterino.Histopathology is considered one of the most important diagnostic tools in medical routine and is characterized by the study of structural and morphological changes of the cells in biological tissues caused by diseases. Currently, the visual assessment of the pathologist is the main method used in the histopathological diagnosis of microscopic images obtained from biopsy samples. This diagnosis is usually based on the experience of the pathologist. The use of computational techniques in the processing of these images allows the identification of structural elements and the determination of inherent characteristics, supporting the study of the structural organization of tissues and their pathological changes. Also, the use of computational methods to improve diagnosis aims to reduce the subjectivity of the evaluation made by the physician. Besides, different tissue characteristics can be mapped through specific metrics that can be used in pattern recognition systems. Within this perspective, the overall objective of this work includes the proposal, the implementation and the evaluation of a methodology for the identification and analysis of histological structures. This methodology includes the specification of a method for the analysis of cervical intraepithelial neoplasias (CINs) from histopathological samples. This work was developed in collaboration with a team of pathologists. Microscopic images were acquired from blades previously stained, containing samples of biopsy examinations. For the segmentation of cell nuclei, a pipeline of morphological operators were implemented. Segmentation techniques based on color were also tested and compared to the morphological approach. For the representation of the tissue architecture an approach based on the tissue layers was proposed and implemented adopting the Delaunay Triangulation (DT) as neighborhood graph. The DT has some special properties that allow the extraction of specific metrics. Clustering algorithms and graph morphology were used in order to automatically obtain the boundary between the histological layers of the epithelial tissue. For this purpose, similarity criteria and adjacency relations between the triangles of the network were explored. The following metrics were extracted from the resulting clusters: mean degree, entropy and the occupation rate of the clusters. Finally, a statistical classifier was designed taking into account the different combinations of clusters that could be obtained from the training process. Values of accuracy, sensitivity and specificity were used to evaluate the results. All the experiments were taken in a cross-validation process (5-fold) and a total of 116 images were used. First, it was evaluated the accuracy in determining the correct presence of abnormalities in the tissue. For this, all images presenting CINs were grouped in the same class. The highest accuracy rate obtained for this evaluation was 88%. In a second step, the discrimination between the following classes were analyzed: Normal/CIN 1; CIN 1/CIN 2, and, CIN 2/CIN 3, which represents the histological grading of the CINs. In a similar way, the highest accuracy rates obtained were 73%, 77% and 86%, respectively. In addition, it was also calculated the accuracy rate in discriminating between the four classes analyzed in this work: the three types of CINs and the normal region. In this last case, it was obtained a rate of 64%.The occupation rate for the basal and superficial layers were the attributes that led to the highest accuracy rates. The results obtained shows the adequacy of the proposed method in the representation and classification of the CINs evolution in the cervical epithelial tissue.
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CAFFARINI, MIRIAM. "Mesoderm stem cells and inflammation: role in the Pathogenesis and potential therapy of selected Gynecological Deseases and primary Myopathies." Doctoral thesis, Università Politecnica delle Marche, 2019. http://hdl.handle.net/11566/263543.
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Le cellule staminali mesenchimali (MSCs) sono un tipo specifico di cellule staminali adulte con un elevato potenziale proliferativo e differenziativo verso cellule specializzate di derivazione mesodermica. Le MSCs svolgono anche una funzione paracrina attraverso il rilascio di molteplici fattori di crescita, chemochine e citochine. Le MSCs si comportanto da sentinelle che percepiscono il microambiente e agiscono di conseguenza, passando da un fenotipo pro-infiammatorio ad uno immunosoppressivo in base ai segnali che ricevono. Nel seguente lavoro sono valutati l’esistenza e il ruolo delle MSCs nella patogenesi e nella potenziale terapia di selezionate patologie ginecologiche con una componente infiammatoria come il leiomioma uterino, la neoplasia intraepiteliale cervicale (CIN) e in miopatie primarie, quali la Distrofia Muscolare di Duchenne (DMD). Nel primo studio, sono state identificate le cellule progenitrici nel leiomioma e nel miometrio sano ed è stata investigata la correlazione tra tali cellule e l’infiammazione nell’insorgenza del leiomioma. I dati suggeriscono che una overespressione di citochine relative all’infiammazione cronica nei progenitori del leiomioma potrebbe favorire un microambiente adeguato per l’insorgenza di questa patologia. Nel secondo studio, le MSCs sono state isolate da cervici di pazienti giovani (yC-MSCs) e pazienti vecchie (oC-MSCs) e i risultati mostrano come la loro immunobiologia sia condizionata dall’età dei donatori, influenzando anche il tasso di regressione della CIN. Inoltre, nel crosstalk con le cellule HeLa, yC-MSCs svolgono maggiormente un ruolo anti-tumorale sostenendo un’infiammazione acuta. L’obiettivo del terzo studio è stato quello di trovare una corretta strategia per aumentare la produzione di distrofina nella DMD mediante terapia genica. Pertanto, i mioblasti isolati da donatori di DMD sono stati trasdotti con la proteina fluorescente verde (GFP) e un vettore lentivirale esprimente l’snRNA per indurre il salto dell’esone; i dati indicano che i mioblasti trasdotti erano abili a differenziare in senso miogenico esprimendo la distrofina funzionale.Mesenchymal stem or stromal cells (MSCs) are a specific type of adult stem cells with an extensive proliferation and differentiation potential towards specialized cells developing from the mesoderm. MSCs are also characterized by paracrine function through the release of multiple growth factors, chemokines and cytokines. MSCs play as sentinel that feel the microenvironment and act consequently, switching from a pro-inflammatory phenotype to an immunosuppressive phenotype according to the signals they receive. In the present work the existence and the role of MSCs in the pathogenesis and potential therapy of selected gynecological diseases with an inflammatory component as uterine leiomyoma, cervical intraepithelial neoplasia (CIN), and in primary myopathies, as Duchenne Muscular Dystrophy (DMD) were evaluated. In the first study, progenitor cells were identified both in leiomyomas and normal myometrium, and the correlation between these cells and inflammation in leiomyoma onset has been investigated. The data suggest that the upregulation of cytokines related to chronic inflammation in leiomyoma progenitors could favour a microenvironment suitable for the onset of this pathology. In the second study, MSCs from cervix of young (yC-MSCs) and old patients (oC-MSCs) were isolated and results show as their immunobiology is affected by the age of donors, influencing in turn the regression rate of CIN. In addition, in the crosstalk with HeLa cells, yC-MSCs play an anti-tumoral role sustaining an acute inflammatory environment. The goal of the third study was to find a correct strategy to enhance the production of dystrophin protein in DMD through gene therapy. Therefore, myoblasts isolated from DMD donor were transduced with green fluorescent protein (GFP) and a lentiviral vector expressing the snRNA to induce exon skipping; data indicate that transduced myoblasts were able to perform myogenic differentiation expressing a functional dystrophin protein.
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Giannoudis, Athina. "Human papillomaviruses in squamous intraepithelial lesions of the cervix." Thesis, University of Liverpool, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.250230.
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El, Hamidi Amina Alarfa Mohamed. "An exploration of molecular markers in prognosis of cervical intraepithelial neoplasia." Thesis, University College London (University of London), 2004. http://discovery.ucl.ac.uk/1446745/.
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Cervical intraepithelial neoplasia (CIN) lesions of the same morphological grade show variable clinical behaviour; some progress and others regress. Currently, there are no biochemical or molecular markers which can distinguish CIN lesions with different prognosis. We have optimised several molecular methods on archival cervical smears and screened a number of molecular markers that may aid prognosis of CIN. By systematically validating different protocols, we have established that crude DNA preparations from a small number of microdissected cells from cervical smears are adequate for various PCR-based investigations. Furthermore, the crude DNA preparations could be further purified and used for PCR-based clonality analysis of the X-linked genes. Using PCR-based clonality analysis of the androgen receptor gene, we have shown that CIN3 and the majority of CIN2 lesions are monoclonal, whereas CINl lesions are polyclonal. Importantly, patients with monoclonal CIN2 show disease persistence or progression, while polyclonal CIN2 regress after treatment and remain negative during follow-up. To further identify molecular markers that are technically easy to apply and potentially suitable for prognosis assessment of all CIN grades, we have investigated the prognostic value of gene deletions. In a pilot study, we screened 12 microsatellite markers, which showed high frequencies of loss of heterozygosity (LOH) in cervical carcinomas, and identified four, including D3S1300 , D3S1260, D11S35 and D11S528, that were significantly associated with CIN persistence or progression. The 4 markers were further investigated in a larger cohort. Combined analysis of LOH at these 4 loci permitted the identification of 22-47% of CIN lesions of various histological grades, that were associated with disease persistence or progression with 100% specificity. LOH at these loci was significantly associated with HPV16 infection. Bioinformatics analysis identified several candidate genes including the fragile histidine triad and progesterone receptor gene that may be the target of deletions.
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Belinson, Suzanne Elizabeth Hartmann Katherine Eubanks. "Association of reproductive history with human papillomavirus and cervical intraepithelial neoplasia severity." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1216.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.Title from electronic title page (viewed Mar. 26, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the School of Public Health (Epidemiology)." Discipline: Epidemiology; Department/School: Public Health.
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Kay, Patti Sheryl. "Typing of human papillomavirus in Western Cape women with cervical intraepithelial neoplasia." Thesis, Cape Technikon, 2002. http://hdl.handle.net/20.500.11838/1471.
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Thesis (MTech (Biomedical Technology))--Cape Technikon, Cape Town, 2002Infection \\'ith specific high risk human papilloma"iruses (HPV) has been shown to play a causal role in the development of ceJVical intraepithelial neoplasia (CIN) and cenical cancer in women. The development of a prophylactic vaccine to immull.ize women against HPV infection would play a \'ita! role in protecting women against HPV infection and ultimately ceMcal cancer. Despite cancer of the cer\'ix being the second most common cancer in South African women, a literature search reveals that few studies have been performed in South Africa on the types of HPV prevalent in women with CIN or cancer ofthe ceMx. HPVs that infect the anogenital tract have also been shown to infect the oral ca\'ity. However, the HPV prevalence rates vary greatly between studies and the significance of the presence ofHPV in the oral ca\'ity is still not understood. The primary objectives of this study were to establish the HPV prevalence rate infecting women with CIN lesions using a sensitive nested polymerase chain reaction (PCR) and to develop a novel restriction fragment length polymorphism (RFLP) method to type the high risk mucosal HPVs detected in these women. The secondary objective of this study was to establish the prevalence rate and HPV types infecting the oral mucosa of women with CIN lesions and to compare these HPV types with those detected in the ceMx. Cemcal punch biopsies were taken from 163 women with CIN lesions and buccal cells were collected from 33 of these participants. DNAwas extracted from the biopsies and buccal samples and PCR using CCRS primers performed to ensure sample adequacy. Nested PCR usmg consensus degenerate primers for HPV was performed on all samples sho\\'wg sufficient amplifiable DNA A novel restriction fragment length pol)morphism (RFLP) method was developed to identify the 10 high risk mucosal HPVs considered human carcinogens of group 1 by the International Agency for Research on Cancer (lARC) as well as HPV 11 which is commonly found in the oral cavity.
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Souza, Carlos Andre Scheler de. "Avaliação dos procedimentos diagnosticos da lesão intra-epitelial escamosa de baixo grau do colo uterino frente a conduta expectante preconizada." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310561.
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Orientador: Luiz Carlos ZeferinoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Atualmente, o manejo preconizado para a neoplasia intra-epitelial cervical grau 1 (NIC1) é expectante. No entanto, a biópsia colpodirigida com este resultado nem sempre representa a totalidade da lesão presente na avaliação inicial, momento em que será decidida a conduta, pois os métodos propedêuticos utilizados rotineiramente podem deixar de diagnosticar lesões de maior grau. A probabilidade de falhas nesta avaliação pode estar relacionada à idade, tabagismo ou achados colposcópicos. Objetivo: Avaliar fatores associados a possíveis falhas da biópsia colpodirigida em mulheres portadoras de LIE-BG no rastreamento do colo do útero. Sujeitos e Métodos: este estudo envolveu mulheres referenciadas em um ambulatório no Centro de Atenção Integral à Saúde da Mulher da Universidade Estadual de Campinas, de janeiro de 2003 a março de 2006, sendo desenvolvidos dois trabalhos. O primeiro analisou o diagnóstico histológico inicial por grupo etário de mulheres com citologia oncológica de rastreamento mostrando lesão intra-epitelial de baixo grau. O segundo analisou a prevalência de NIC 2 ou lesões mais graves em mulheres submetidas à cone do colo uterino, com diagnóstico histológico prévio de NIC 1 obtido por biópsia dirigida por colposcopia. Resultados: Foram analisadas 825 mulheres no primeiro artigo. Destas, 10% (82) apresentaram resultado histológico do tipo NIC 2 ou de maior gravidade, mas a freqüência deste resultado não variou com o aumento da idade. Outras 256 (31%) não foram submetidas à biópsia por não apresentarem lesão suspeita, sendo que a freqüência destas mulheres tendeu a aumentar com a idade. No segundo artigo, a prevalência de 19% de resultados NIC 2 ou de maior gravidade foi obtida na análise histológica do cone de colo uterino. No entanto, este achado não se associou com idade, hábito de fumar ou tamanho da lesão colposcópica. Conclusão: A maioria das mulheres com LIE-BG não apresentou lesões mais graves do que NIC 1 na avaliação inicial, embora tenha existido uma prevalência relevante de resultados histológicos NIC 2 e NIC 3, considerando-se os dois estudos realizados. Esta prevalência não foi maior nas mulheres com idade mais avançada, podendo a conduta expectante ser adotada neste grupo etário. Também não houve associação entre hábito de fumar, achados colposcópicos e presença de NIC 2 ou NIC 3 em mulheres com biópsia prévia indicando NIC 1. Assim, o principal fato a ser considerado para a adoção da conduta expectante é a garantia de que haverá adesão ao seguimento. Caso contrário, recomenda-se encaminhar imediatamente para avaliação colposcópica
Abstract: Currently, the recommended management for cervical intraepithelial neoplasia grade 1 (CIN 1) is conservative. However, the histological diagnosis defined by colposcopy-guided biopsy could not represent all the lesions that exist at the time of initial evaluation, because the usual diagnostic methods would not detect higher-grade lesions. Age, smoking and colposcopic findings could be related to fails of this initial evaluation. Objectives: to evaluate associated factors to failures on diagnoses defined by colposcopy-guided biopsy in women with lowgrade squamous lesions (LSIL). Subjects and Methods: this study analyzed 825 women evaluated from January 2003 to March 2006 in the State University of Campinas (UNICAMP), Brazil. As result, two papers were made. The first analyzed the histological diagnosis of women with LSIL by age. The second analyzed the prevalence of CIN2 or more severe lesion at the LEEP in women previously diagnosed as CIN 1 by colposcopy-guided biopsy. Results: In the first paper, 10% of the women had CIN 2 or more severe lesion, but this result had not associated with age. In the other paper, a 19% prevalence of CIN 2 was found at the histological analysis of the LEEP. However, this finding did not had associated with age, smoking or colposcopic findings. Conclusion: The majority of the analyzed women with LSIL did not have higher-grade lesion at initial evaluation, yet the prevalence of CIN 2 or CIN 3 was relevant. This prevalence had not increased with age. Either, there was not association between smoking, colposcopic findings and CIN 2 or CIN 3 diagnosis in women with CIN 1 previously diagnosed. So, the most important fact to be considered for adoption of conservative management is to guarantee adhesion for follow-up. If this is not possible, reference to colposcopy is recommended
Mestrado
Tocoginecologia
Mestre em Tocoginecologia
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Sidhu, Harmin Kaur. "Evaluation of a cytotoxic drug delivery system for the treatment of cervical intraepithelial neoplasia." Thesis, Queen's University Belfast, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.484065.
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Magno, Valentino Antônio. "Avaliação da segurança e efetividade da termocoagulação no tratamento da neoplasia intraepitelial cervical de alto grau." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/118326.
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Base Teórica: O Câncer cervical é uma neoplasia maligna comum no mundo, especialmente nos países menos desenvolvidos. O diagnóstico e tratamento de lesões intraepiteliais de alto grau do colo do útero através de programas de rastreamento provaram ser eficazes na redução da mortalidade por câncer. Diferentes métodos estão disponíveis para o tratamento de lesões de alto grau. Métodos de excisão são geralmente preferidos em todo o mundo, porque eles são seguros e fornecem uma quantidade grande de material para o patologista, mas eles exigem uma estrutura que não é sempre disponível nos países em desenvolvimento. Métodos ablativos também são usados para tratar lesões de alto grau com altas taxas de sucesso sendo, geralmente, mais práticos e menos dispendiosos. A termocoagulação (cold coagulation) é um método ablativo que usa um instrumento portátil e de baixo custo que pode ser uma boa opção de tratamento, especialmente em países com recursos limitados. Objetivo: Neste artigo avaliamos a efetividade e a segurança da termocoagulação para o tratamento de lesões intraepiteliais cervicais de alto grau. Métodos: 52 mulheres de 25 a 59 anos com lesão intraepitelial de alto grau confirmada em biópsia e sem tratamento prévio foram convidadas a fazer parte deste estudo de janeiro de 2013 a dezembro de 2013. Resultados: A idade médiafoi de 34.2 anos. Um total de 52 pacientes foram tratadas com a termocoagulação sendo 61,5% com neoplasia intraepitelial cervical grau 3 (NIC 3) e 38,5% NIC 2. Após 6 meses, nenhuma das pacientes teve suspeita de lesão de alto grau persistente no exame citopatológico ou colposcopia. Após 12 meses, 2 pacientes tiveram NIC 3 confirmada em biópsia. A taxa de cura após a termocoagulação foi de 96,1% após um ano (IC 87.9% a 99.4%.). Nenhum efeito adverso grave foi documentado durante ou após o tratamento. Conclusão: A termocoagulação é um método seguro e eficaz para o tratamento de lesões intraepiteliais de alto grau. Este tratamento pode ser uma alternativa útil especialmente em países com recursos limitados. Estes são os primeiros resultados publicados utilizando a termocoagulação para o tratamento da displasia cervical de alto grau no Brasil encontrados na literatura.Background: Cervical Cancer is a common malignant neoplasia in the world, specially in poor countries. The diagnosis and treatment of high grade intraepithelial lesions (HSIL) of the cervix through screening programs proved to be effective in reducing cancer mortality. Different methods are avaiable for treating high grade lesions. Excisional methods are usually preferred all over the world because they are safe and give a lot of material to the pathologist but they require a structure to be performed that is not always avaiable in developing countries. Ablative methods are also used to treat HSIL with extremely high rates of success and they are usually more practical and less expensive. Cold Coagulation is an ablative method that uses a portable and inexpensive instrument that can be a good treatment choice specially in countries with limited resources. Objective: In this article we present the data to evaluate the effectiveness and safety of the cold coagulation to treat high grade cervical intraepithelial lesions. Methods: 52 women from 25 to 59 years old with HSIL confirmed in a biopsy and no previous treatment were invited to be part of this study from January 2013 to December 2013. Results: The mean age of the patients was 34.2 years old. A total of 52 patients were treated with cold coagulation being 61.5% with Cervical Intraepithelial Neoplasia grade 3 (CIN3) and 38.5% CIN2. After 6 months none of the patients had any suspicion of persistent high grade lesion at citopathologic exam or colposcopy. After 12 months, 2 patients had CIN3 confirmed in a biopsy. The cure rate after cold coagulation was 96.1% after 1 year (CI 87.9% a 99.4%). No serious adverse effect was documented during or after the treatment. Conclusion: Cold Coagulation is a very effective and safe way of treating HSIL. It can be anusefull alternative specially in countries with limited resources. These are the first published results using cold coagulation for the treatment of HSIL in Brazil.
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Monteiro, Junior Orlando. "Neoplasia intra-epitelial cervical em mulheres soro-positivas para o vírus da imunodeficiência humana /." Botucatu : [s.n.], 2001. http://hdl.handle.net/11449/93112.
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Orientador: Paulo TraimanResumo: Objetivando estudar a prevalência de neoplasia intra-epitelial cervical (NIC) em mulheres soro-positivas para o vírus da imunodeficiência humana (HIV) ao compará-las com um grupo controle de mulheres soro-negativas, foi realizado um trabalho retrospectivo em que foram avaliadas 86 mulheres HIV positivas e 86 mulheres HIV negativas, que freqüentaram um serviço público de acompanhamento em DST/AIDS na cidade de Campo Grande, Mato Grosso do Sul, Brasil. Foram realizadas avaliações citológicas pelo Papanocolaou, colposcopias e biópsias quando indicadas. Encontrou-se uma prevalência maior de NIC no grupo de mulheres HIV positivas em comparação ao grupo de mulheres HIV negativas, e esta diferença foi estatisticamente significativa. Conclui o autor que, sendo o câncer do colo uterino uma patologia previnível e com o atual aumento da expectativa de vida das pacientes HIV positivas, este grupo de mulheres merece atenção ginecológica diferenciada com consultas mais frequentes e livre acesso à colposcopia.
Abstract: Objetiving to study the prevalence of cervical intraepithelial neoplasia (CIN) in human immunodeficiency virus (HIV) - infected women and to compar with a group control of seronegative women, it was realized a retrospective study being assessed 86 HIV - infected and 86 HIV - unifected women, who were attended in a public service of accompaniment in TSD/AIDS in Campo Grande City, Mato Grosso do Sul, Brazil. Were realized evolution cytologic for the Papanicolaou test, colposcopy and biopsies, when indicated. It was found a prevalence of CIN significantly greater in HIV - seropositive women than in seronegative women. In conclusion, being the cervical cancer a pathology that can be prevented and with the current increase of the life's expectative of the HIV - seropositive women, this group of women needs a better gynecologic atenttion with visits and Papanicolaou smears more often and free access to colposcopy.
Mestre
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BADRIKIAN, LAURENCE. "Neoplasies cervicales intraepitheliales et microcarcinome du col : analyse de 93 vaporisations de cin2 et cin3 et de 52 conisations." Clermont-Ferrand 1, 1989. http://www.theses.fr/1989CLF13082.
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OLIVEIRA, Talita Helena Araújo de. "Avaliação e correlação do perfil de expressão do oncogene E5 do papilomavírus humano e do miRNA- 203 do hospedeiro na carcinogênese cervical." Universidade Federal de Pernambuco, 2016. https://repositorio.ufpe.br/handle/123456789/19531.
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CNPQ
O HPV é o principal fator transformadordo câncer cervical. No seu ciclo viral é expressa a oncoproteína E5, responsável por várias alterações na célula hospedeira e,foi sugerido in vitro, que ela altera a proliferação celular através da regulação negativa do microRNA-203, que em condições normais atua inibindo a proliferação e condicionando a diferenciação dos queratinócitos. Entretanto os mecanismos que envolvem E5 e o microRNA-203 ainda não estão bem elucidados. Este estudo tem como objetivo avaliar o perfil de expressão da oncoproteína E5 e do microRNA-203 em biópsias de colo uterino, observando a existência de correlação entre ambos. A expressão gênica relativa do microRNA-203 e E5 nas amostras clínicas (n=90), referente a todas as etapas da carcinogênese cervical (Normal, NIC I, NIC II, NIC III e câncer), foi obtida por qPCR.As análises mostraram uma diminuição do perfil de expressão do microRNA-203 no câncer em comparação com amostras normais (p<0,01) enquanto o RNAm de E5 do HPV 16 aumentou sua expressão em NIC III e no câncer em relação a lesões de baixo grau (NIC I) (p<0,001 e p<0,01, respectivamente). Os resultados apontam que o microRNA-203 está regulado negativamente no câncer cervical, porém sem correlação estatisticamente significante com a expressão de E5. O perfil apresentado nos diferentes estágios sugere que omicroRNA-203e o oncogene E5 são capazes de diferenciar estágios da carcinogênese cervical.
The Human papillomavirus (HPV) is the main transforming factor in cervical cancer. The HPV expresses the oncoprotein E5 which is responsible for several changes in the host cells and recent in vitro studies have suggested that it plays a role in the regulation of cell proliferation through microRNA-203. This microRNA acts by inhibiting cell proliferation and stimulating cell differentiation in normal conditions. However, the mechanisms involving E5 and microRNA-203 are not yet well elucidated. The aim of the present study is to evaluate both E5 and microRNA-203 expression profiles in biopsies of women from Pernambuco andobserve if there is any correlations between them. Expression of microRNA-203 in clinical samples (n=90), observed at all carcinogenic process (Normal, CIN I, CIN II, CIN III and cancer), was obtained by real-time qPCR. The analysis here performed demonstrates a decreased expression of microRNA-203 in cancer samples when compared to the normal ones (p<0,01) while E5 increased its expression in CIN III and cancer when compared to low-grad lesion (CIN I) (p<0,001 and p<0,01, respectively). Our data shows that miR-203 is downregulated in cancer, although no statistical significant correlation was found between its expression and E5.Both expression profiles suggest their ability to differentiatelesions.
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McCarron, Paul A. "Design and evaluation of polymeric drug delivery systems for the treatment of cervical intraepithelial neoplasia." Thesis, Queen's University Belfast, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359100.
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Veiga, Fernanda Rangel da. "Prevalência de lesão intra-epitelial escamosa de alto grau e câncer cervical em pacientes com colpocitologia oncóticasugestiva de alto grau e colposcopia insatisfatória sem lesão visível." Instituto Fernandes Figueira, 2008. https://www.arca.fiocruz.br/handle/icict/3536.
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Previous issue date: 2008Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Departamento de Ensino. Programa de Pós-Graduação em Saúde da Criança e da Mulher. Rio de Janeiro, RJ, Brasil
Introdução: O câncer de colo uterino ainda é considerado um grave problema de saúde pública no Brasil. Algumas recomendações para o controle desta doença no país são baseados em opiniões de especialistas e, no caso de pacientes com colpocitologias sugestivas de lesão intra-epitelial escamosa de alto grau (HSIL) e colposcopia insatisfatória sem lesão visível, consistem em repetir a colpocitologia após três meses. No Setor de Patologia Cervical do Instituto Fernandes Figueira/ FIOCRUZ, estas pacientes são encaminhadas diretamente para conização, na intenção de confirmar o diagnóstico e, caso presente HSIL, já se constituir no tratamento destas lesões. Objetivo: Medir a prevalência de HSIL e câncer em pacientes com a primeira colpocitologia sugestiva de HSIL e colposcopia insatisfatória sem lesão visível, além de identificar uma faixa etária ou grupos em que esta prevalência seja maior, no intuito de contribuir para a discussão sobre uma conduta clínica mais efetiva e que diminua a probabilidade de ocorrência de perdas antes do diagnóstico e tratamento adequados nesta situação. Material e método: Estudo transversal realizado através de pesquisa em banco de dados de pacientes recebidas no Setor de Patologia Cervical no período de dezembro de 1989 a abril de 2007 referidas pela rede básica de saúde para colposcopia, obtendo o diagnóstico final através dos laudos histopatológicos das peças de conização. Resultados: Foram incluídas 65 pacientes na situação descrita e encontrado percentual de 33,8% (IC95% 23,1- 45,9%) de HSIL e 4,6% (IC95% 1,1- 12,0%) de câncer confirmados histologicamente. Os demais casos apresentaram lesão intra-epitelial escamosa de baixo grau (LSIL - 26,1%, IC95% 16,5- 37,8%), displasia glandular (1,5%, IC95% 0,07- 7,35%)e ausência de doença (33,8%, IC95% 23,1- 45,9%). Não foi encontrada diferença estatisticamente significativa na razão de prevalência de HSIL e câncer em grupos de mulheres segundo estratos de idade abaixo e acima de 45 anos e entre mulheres soropositivas e soronegativas para HIV. Conclusão: A prevalência de HSIL ou câncer encontrada não parece suficiente para defender a conduta de encaminhá-las de imediato para conização a fim de investigar o canal cervical. Porém, são necessários ensaios clínicos randomizados para que possamos saber qual a conduta mais adequada na situação em estudo.
Introduction: Cervix cancer is a serious public health problem in Brazil. Some of the recommendations for controlling the disease in the country are based on the opinion of specialists. In patients with unsatisfactory colposcopy with no visible lesion and cervical cytology suggesting high-grade squammous intraepithelial lesion (HSIL), the recommendation is to repeat cervical cytology after three months. In the Cervical Pathology unit at Instituto Fernandes Figueira/ FIOCRUZ, these patients are directly subjected to conization in order to confirm diagnosis and to excise the lesions found, if HSIL is verified. Objectives: To assess prevalence of HSIL and cancer in patients with unsatisfactory colposcopy with no visible lesion and first cervical cytology suggestive of HSIL, and to identify an age group or other groups with higher prevalence in order to contribute to the discussion about a more effective clinical approach that will also prevent patients from abandoning follow-up before full diagnosis and treatment. Method: Cross-sectional study with data from the Cervical Pathology unit database on patients treated between December 1989 and April 2007 who were referred to the unit for colposcopy by the primary healthcare network. Final diagnosis was obtained through histopathological examination of conization specimens. Results: Of the 65 patients studied, 33,8% (CI95% 23,1- 45,9%) had HSIL, and 4,6% (CI95% 1,1- 12,0%) had cancer confirmed by histological examination. The other patients were diagnosed as having low-grade squammous intraepithelial lesion (LSIL - 26,1%, CI95% 16,5- 37,8%), glandular dysplasia (1,5%, CI95% 0,07- 7,35%), and absence of disease (33,8%, CI95% 23,1- 45,9%). This study did not find statistically significant difference of the prevalence ratio of HSIL and cancer between age groups of more than 45 and less than 45 years of age, and between women tested positive or negative for HIV. Conclusion: The prevalence of cancer and HSIL found in this study does not seem to be enough to justify direct referral for conization to investigate the cervical canal. Nevertheless, randomized clinical trials are necessary to determine an approach that would be more adequate in this situation.
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Shoultz, David Arthur. "Human papillomavirus (HPV) serum antibodies and their association with clinical manifestations of HPV infection in a cohort of sexually-active women /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/10930.
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Likes, Wendy. "Feasibility study of liquid-based cytology for post-treatment surveillance of patients with vulvar intraepithelial neoplasia." View the abstract Download the full-text PDF version, 2009. http://etd.utmem.edu/ABSTRACTS/2009-024-Likes-index.htm.
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Thesis (Ph.D.)--University of Tennessee Health Science Center, 2009.Title from title page screen (viewed on August 27, 2009). Research advisor: Donna Hathaway, PhD. Document formatted into pages (ix, 43 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 34-37).
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Manley, Kristyn. "The diagnosis and management of cervical intraepithelial neoplasia in women with a transformation zone type 3." Thesis, University of Bristol, 2018. http://hdl.handle.net/1983/a8b57946-e126-4131-bc00-120214e12897.
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Twenty percent of colposcopic assessments are inadequate due to a type 3 transformation zone (TZ3). Despite this, the literature relating to this finding is sparse. Management is guided by the referral screening test and, in this thesis, I have shown that the presence of a TZ3 is the strongest predictor of false positive cervical screening results. Analysis of colposcopists’ decision-making, both locally and nationally, identified heterogeneity of care in women with low grade cytology and a TZ3; total length and technique of cytological follow-up were affected by anxiety of missing a cancer and paucity of guidance, suggesting a need for a national consensus opinion. To date, the effectiveness of different cytological sampling techniques in a TZ3 assessment have not been evaluated. In the UK, routine cervical screening is completed by a Cervex-Brush alone. In my thesis, the addition of a cytobrush increased the yield of endocervical cells but this was not associated with increased predictability of CIN2+. This finding is relevant for resource allocation as I propose, that cytological follow-up with a Cervex-Brush alone can be safely undertaken in a primary care setting. My findings suggest women with high grade cytology and a TZ3 should be offered a LLETZ as 80% will have CIN2+. I have also reported, for the first time, that women with low grade cytology, high risk HPV and a TZ3 have double the risk of CIN2+ (36.7%) when compared to women where the TZ is visible. In these women I propose the use of HPV biomarkers (p16 and Ki-67) in combination with liquid based cytology; these biomarkers provide a >99% sensitivity for CIN2+ and improve the specificity of screening from 19.3% to 71.7%. When compared to dual-stained cytology, neither HPV 16/18 genotyping nor p16 & Ki67, in combination with endocervical curettings, demonstrated an equivocal sensitivity.
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Segati, Kelly Deyse. "Associação entre Chlamydia trachomatis e HPV com a gravidade da neoplasia cervical." Universidade Federal de Goiás, 2012. http://repositorio.bc.ufg.br/tede/handle/tede/5878.
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Infection with Chlamydia trachomatis (CT) may be associated with persistent carcinogenic HPV types and the development of cervical neoplasia. There are indications that detection of CT serum antibodies rather than DNA is a better measure of cumulative exposure to CT or of exposure occurring several years prior to the development of cervical disease. The objective of this study was to compare the positivity for CT by ELISA and PCR and to correlate with the severity of cervical neoplasia in women with abnormal cervical smear. Between February 2007 and March 2009, 136 women were referred to the colposcopy clinic at the Santa Casa de Misericordia in Goiânia-GO. HPV DNA was detected by the polymerase chain reaction (PCR) and genotyping was performed by reverse line-blot hybridization assay. CT seropositivity was tested by ELISA for the detection of IgG antibodies and the detection of CT was done by PCR to amplify a sequence in the cryptic plasmid generating a fragment of 512 base pairs. The total prevalence of HPV infection was 85.2%. Seropositivity for CT was 26%. Thirty-one women 26.7 were tested positive for CT antibodies and HPV-DNA. Of these 10.3% had diagnosis of cervical intraepithelial neoplasia grade 1 (CIN1) or cervicitis, while 16.3% had histological diagnosis of CIN2 worse diagnosis. When employed PCR test positivity was found to be 8.8%. Eleven women 9.48% were tested positive for CT and HPV DNA. Of these 5.1% had diagnosis of cervicitis or CIN1 and 4.3% had a diagnosis of CIN2 or worse diagnosis. The agreement between serology and PCR tests for CT was considered poor (kappa=0.10 IC 95% 0.69-7.9). Taking as reference the cases negatives for HPV and CT, a positivity for HPV and CT seropositivity was significantly associated with a diagnosis of CIN2 or worse diagnosis, for all HPV types (OR=11.9 IC=2.00-91.5 p=0.0009) and types 16 and 18 (OR=7.50 IC=0.91-76.28 p=0.02). Significant association was observed after adjustment for HPV. A Borderline significance was observed considering other HPV types (OR=7.50 IC=0.91-76.28 p=0.02). CT seropositivity was associated with CIN2 worse diagnosis in women infected by HPV, mainly when the types 16 and 18 were involved. This study did not show any association between CT infection detected by PCR and CIN2 or worse diagnosis. These data support the hypothesis that seropositivity for CT compared to PCR positivity in HPV positive women, especially for types 16 and 18, is a better measure of previous exposure, which reflects a higher probability of association with the severity of cervical neoplasia.
A infecção por Chlamydia trachomatis (CT) pode estar associada com a persistência dos tipos de Papilomavírus humano (HPV) oncogênicos e desenvolvimento da neoplasia cervical. Há indicações de que a detecção de CT por sorologia seja uma melhor medida de exposição cumulativa ou da exposição passada quando comparada a detecção pela reação da polimerase em cadeia (PCR). O objetivo deste estudo foi comparar a positividade para CT pelos métodos de ELISA e PCR e relacionar com a gravidade da neoplasia cervical em mulheres com anormalidades citológicas. Entre fevereiro de 2007 e março de 2009, 136 mulheres, foram encaminhadas à Clínica de Colposcopia na Santa Casa de Misericórdia em Goiânia-GO por exame citológico alterado. A detecção de DNA do HPV foi realizada por PCR utilizando os iniciadores PGMY09/PGMY11, e a genotipagem foi realizada por hibridização reversa em pontos. A positividade para CT foi avaliada por ELISA para detecção de anticorpos IgG e por PCR empregando iniciadores cujo alvo é uma região de plasmídeo críptico, gerando um fragmento de aproximadamente 512 pares de bases. A prevalência total da infecção por HPV foi 85,2%. A positividade para CT por sorologia foi de 25%. Trinta e uma amostras 26,7% foram positivas para HPV e CT. Destas 10,3% tinham diagnóstico de neoplasia intraepitelial cervical grau 1 (NIC1) ou cervicite, enquanto 16,3% tinham diagnóstico histológico de NIC 2 ou pior diagnóstico. Quando empregado o teste de PCR a positividade encontrada foi de 8,8%. Onze amostras 9,48% foram positivas para HPV e CT por PCR, sendo que 5,1% das pacientes apresentavam diagnóstico de NIC1 ou cervicite e 4,3% tinham diagnóstico de NIC 2 ou pior diagnóstico. A concordância entre os testes de sorologia e PCR para CT foi considerado ruim (kappa=0,10 IC 95% 069-7.9). Tomando como referência casos negativos para HPV/CT, a positividade para HPV/CT por sorologia foi significantemente associada com diagnóstico de NIC2 ou pior diagnóstico, para todos os tipos de HPV (OR=11.9 IC=2.00-91.5 p=0.0009) e para os tipos 16 e 18 (OR=16.25 IC=2.28-148.57 p=0.0005). Uma associação limítrofe foi observada considerando outros tipos de HPV (OR=7.50 IC=0.91-76.28 p=0.02). Houve associação estatisticamente significante após o ajustamento para infeção por HPV entre as infecções pelos tipos 16 e 18 e soropositividade para CT com a gravidade da neoplasia cervical. Quando empregado o teste de PCR, não houve associação entre a coinfecção HPV/CT e a gravidade da neoplasia cervical. Estes dados reforçam a hipótese de que a soropositividade para CT quando comparada a positividade por PCR em mulheres HPV positivas, especialmente para os tipos 16 e 18, é uma melhor medida de exposição anterior, o que reflete maior probabilidade de associação com a gravidade da neoplasia cervical.
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Carvalho, Michelle Garcia Discacciati de. "Valor preditivo da avaliação do DNA e da expressão dos genes E6/E7 do papilomavírus humano na evolução da neoplasia intraepitelial cervical de grau 2." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310571.
Full textAbstract:
Orientadores: Luiz Carlos Zeferino, Sílvia Helena Rabelo dos SantosTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A avaliação das taxas de evolução da NIC 2 e a identificação de aspectos clínicos e marcadores preditivos de regressão desta lesão podem identificar as mulheres que se beneficiariam de uma conduta expectante e seguimento periódico. Objetivo: Avaliar alguns fatores clínicos e moleculares associados à progressão e regressão da NIC 2, em mulheres submetidas à conduta expectante. Sujeitos e Métodos: O estudo foi do tipo coorte e incluiu 50 mulheres com diagnóstico de NIC 2 confirmado por biópsia, após serem referenciadas ao Centro de Atenção Integral à Saúde da Mulher (CAISM), Universidade Estadual de Campinas (UNICAMP), por apresentaram exame citopatológico mostrando lesão intraepitelial escamosa de baixo grau (LIEBG). Estas mulheres foram acompanhadas por 12 meses, com consultas trimestrais para avaliação citológica e colposcópica. Na admissão, foram coletadas amostras para a realização de testes de genotipagem de HPV, os quais foram realizados no Instituto Ludwig de Pesquisa Sobre o Câncer; e também para testes de detecção de RNA mensageiro dos genes E6/E7 dos HPV tipos 16,18,31,33 e 45, realizados no Laboratório Salomão & Zoppi. Os resultados deste estudo estão sendo apresentados em dois artigos. O primeiro avaliou a frequência de progressão, persistência e regressão da NIC2, como também testou se a idade da mulher no diagnóstico e idade ao início da atividade sexual variaram com a evolução da lesão. O segundo artigo avaliou a associação dos tipos e espécies de HPV e da expressão dos genes virais E6 e E7 com a evolução de NIC 2. Resultados: Ao final de 12 meses houve 74% de regressão, 24% de progressão de NIC 2 para NIC 3, e um caso de persistência da NIC 2. A maioria dos casos regrediu nos primeiros seis meses de seguimento. Não foi observada associação entre a evolução de NIC 2 e a idade ou início da atividade sexual em mulheres submetidas à conduta expectante. As taxas de regressão da NIC 2 aos 12 meses de seguimento, para mulheres com HPV da espécie alfa-9, comparada com outras espécies ou HPV negativo foram 69,4 e 91,7% respectivamente, sendo que esta diferença foi estatisticamente significativa ao longo do seguimento. A taxa de regressão de NIC 2 aos 12 meses foi de 68,3% para mulheres com teste positivo para RNA mensageiro de E6/E7 e 82,6% para mulheres com teste negativo para este marcador, mas esta diferença não foi estatisticamente significativa. Conclusão: A maioria da NIC 2 diagnosticada por biópsia em mulheres selecionadas por exame citológico com diagnóstico de lesão LIBG regride em até 12 meses. Mulheres infectadas por tipos de HPV da espécie alfa-9, especialmente o HPV 16, são menos propensas a ter regressão da NIC 2 ao final de 12 meses de seguimento. Os resultados não demonstraram associação entre a expressão de genes virais E6/E7 com a regressão ou progressão da NIC 2
Abstract: The evaluation of CIN 2 outcome rates and identification of clinical features and predictive markers of the lesion regression can identify women who would benefit from an expectant management and regular monitoring. Objective: To evaluate the clinical and molecular factors associated with progression and regression of CIN 2 in women undergoing expectant management. Subjects and Methods: This cohort study included 50 women with diagnosis of CIN 2 confirmed by biopsy after being referenced to the Center of Integral Attention to Women's Health, State University of Campinas, with Pap smear showing low-grade lesion (LSIL). These women were followed for 12 months with three-monthly controls visits for cytological and colposcopic evaluation. On admission, samples were collected to perform HPV genotyping, which was held at the Ludwig Institute and also for the detection of E6/E7 mRNA, which was performed in the laboratory Salomão & Zoppi. The results of this study are presented in two articles. The first assessed the frequency of progression, persistence and regression of CIN2, comparing these rates with clinical factors such as woman's age and age at first sexual intercourse. The second evaluated the association between CIN 2 evolution with the HPV species and expression of viral genes E6 and E7. Results: At the end of the 12 months of monitoring, there was 74% of regression, 24% of progression to CIN 3 and only one case of persistence of CIN 2. The most of the CIN 2 regresses during the first six months of follow-up. However, there was no statistically significant association between the women' age and the age at first sexual intercourse. The rate of CIN 2 regression at 12 months follow-up for women with HPV alpha- 9 compared with another HPV species groups or HPV negative were respectively 69,4% and 91,7%, and the difference up to 12-month follow-up was statistically significant. The CIN 2 regression rate at 12-month follow-up for women with positive E6/E7 mRNA was 68.3%, and for negative was 82.6%, but the difference up to 12-month follow-up was not statistically significant. Conclusion: The majority of CIN 2 diagnosed by biopsy in women with previous cervcial smear showing LSIL regresses after 12 months. Women infected with HPV alpha-9, which includes HPV 16, are less likely to have CIN 2 regression over 12 months of follow-up. The results showed no association between the expression of viral genes E6 and E7 with the regression or progression of CIN 2
Doutorado
Ciencias Biomedicas
Doutor em Tocoginecologia
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Fachini, Ana Maria Dias 1980. "Fatores de risco para diagnóstico histológico de lesão escamosa de alto grau em mulheres com resultado citológico de lesão de baixo grau = Risk factors for histological outcome of high-grade lesions in women with LSIL as shown by screening with cytology." [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310557.
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Orientador: Luiz Carlos ZeferinoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: A LIE-BG tem maior prevalência em mulheres jovens e a conduta expectante deve ser considerada ao invés da realização de testes para detecção de DNA-HPV. Mulheres com LIE-BG podem apresentar NIC 2 ou NIC 3 e, por este motivo, a conduta frente a este resultado deve selecionar as mulheres com maior risco para lesões mais graves. Objetivos: Avaliar a associação de alguns fatores de risco para diagnóstico histológico de lesão de alto grau em mulheres com resultado citológico de LIE-BG. Métodos: Este estudo incluiu 791 mulheres resultado de LIE-BG na citologia de rastreamento e que foram encaminhadas para colposcopia imediata. Ausência de neoplasia foi considerado o diagnóstico final em 235 mulheres nas quais a colposcopia foi normal. Outras 92 mulheres foram submetidas a excisão da zona de transformação. As variáveis analisadas foram: idade da mulher, idade de início de atividade sexual (IAS), tempo de atividade sexual (TAS) e adimplência ao rastreamento do câncer do colo útero. Resultados: Observou-se maior prevalência de NIC 3 e menor prevalência de casos sem neoplasia e NIC 1 nas mulheres com maior TAS. Inadimplência com o rastreamento está associada com maior prevalência de NIC 3 (OR=2.91; 1.27-6.63). A análise multivariada mostrou que NIC 3 está fortemente associado com TAS >10 anos quando comparado com TAS < 4 anos (OR=8.33; 1.82-33.33) e 5-9 anos (OR=7.69; 1.85-33.33) e essa associação foi limítrofe para a inadimplência com o rastreamento (OR=2.39; 0.96-5.92). A IAS não esteve associada a nenhum dos desfechos estudados. Conclusões: Mulheres com resultado citológico de LIE-BG têm maior probabilidade de revelar NIC 3 quando elas têm mais de 10 anos de tempo de atividade sexual e quando elas estão inadimplentes com o rastreamento do câncer do colo do útero. Essas mulheres devem ser encaminhadas imediatamente para colposcopia
Abstract: Introduction: LSIL shows higher prevalence in young women and conservative management should be considered other than HPV testing. Women with LSIL cytology may reveal CIN2 or CIN3 and for that reason the management should select the women with the higher risk for more severe lesions. Objectives: This study aimed to evaluate the association of some factors with histological outcome of women showing cytological LSIL. Methods: This study included 791 women with screening cytology showing LSIL who were referred to immediate colposcopy. The final diagnosis was considered "no neoplasia" for 235 women who had normal colposcopy. Other 92 women were undergone to excision of transformation zone. The variables analysed were woman's age, age of first sexual intercourse (FSI) and interval since FSI and screening compliance. Results: Higher interval since de FSI was associated with higher prevalence rate for CIN3 and lower prevalence rates for "no neoplasia" and CIN1. No screening compliance was associated with higher prevalence of CIN3 (OR=2.91; 1.27-6.63). Multivariate analysis showed that CIN 3 outcome was strongly associated with interval since FSI >10 years taking as reference <4 years (OR=8.33; 1.82-33.33) and 5-9 years (OR=7.69; 1.85-33.33) and it showed borderline association with no screening compliance (OR=2.39; 0.96-5.92). Age of FSI was not associated with any diagnosis. Conclusions: Women with LSIL screening cytology have higher probability to reveal CIN3 outcome when they have 10 or more years of since FSI and when they are non-compliant with cervical cancer screening. These women should have immediate colposcopy
Mestrado
Oncologia Ginecológica e Mamária
Mestre em Ciências da Saúde
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Guarisi, Renata. "Tabagismo, infecção pelo papilomavirus humano e o desenvolvimento de neoplasia intra-epitelial cervical." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310529.
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Orientadores: Luis Otavio Zanatta Sarian, Sophie Françoise Mauricette DerchainTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Objetivo: Avaliar os efeitos do tabagismo na prevalência da infecção pelo papilomavírus humano de alto risco oncogênico (HR-HPV) e neoplasia intra-epitelial cervical (NIC). Avaliar prospectivamente os efeitos do tabagismo sobre a aquisição de HR-HPV e desenvolvimento de NIC em mulheres sem lesão histológica na primeira consulta. Sujeitos e métodos: Foram avaliadas 12.114 mulheres incluídas no estudo Latin American Screening (LAMS) entre janeiro de 2002 a novembro de 2003, em Campinas, São Paulo, Porto Alegre e Buenos Aires. Foram formados três grupos: 1) não tabagistas (n=7.499), tabagistas (n=2.706) e 3) ex-tabagistas (n=1.871). Para o seguimento prospectivo de 36 meses foram selecionadas mulheres com pelo menos um exame alterado na primeira consulta, mas que não tinham lesão histológica, e 10% daquelas com todos os exames normais, totalizando 1.011 mulheres. Um grupo formado por 150 mulheres com citologia compatível com células escamosas atípicas (ASC) ou lesão intra-epitelial de baixo grau (LSIL) e colposcopia normal foi estudado separadamente. A análise inicial avaliou a relação entre a história de tabagismo e outros fatores epidemiológicos com a prevalência de infecção por HR-HPV e NIC. As mulheres foram examinadas a cada seis meses com colposcopia, captura de híbridos 2 e colpocitologia oncológica. Resultados: A diferença mais importante entre os grupos foi a prevalência de HR-HPV entre tabagistas (21,7%) quando comparadas a não tabagistas (16,5%) e ex-tabagistas (13,5%). Teste HR-HPV positivo (OR=9,69; 95%CI=5-18,79), citologia com lesão intra-epitelial de alto grau (OR=40,52; 95%CI = 8,52-192,6) e história de não ter realizado Papanicolaou no passado (OR=2,65; 95%CI=1,21- 5,79) estiveram associados ao maior risco de NIC 2 ou pior na consulta inicial. A incidência de anormalidades no Papanicolaou durante o seguimento foi mais freqüente nas tabagistas (5,8%) quando comparadas às ex-tabagistas (4,8%) e não tabagistas (1,7%). Durante o seguimento, HR-HPV+ na consulta inicial aumentou significativamente o risco de incidência de Papanicolaou anormal, independentemente da história de tabagismo. Tabagismo foi um significante preditor de incidência de HR-HPV durante o seguimento, e ter HR-HPV+ na consulta inicial, ser tabagista e ex-tabagista foram fatores de risco independentes para incidência de NIC2 ou pior. No grupo ASC/LSIL, apenas HR-HPV + inicial esteve associado ao risco de desenvolver NIC durante o seguimento de 36 meses (HR=3,42; 95CI%=1,11-9,43). Mulheres tabagistas tiveram maior risco de NIC de alto grau ou câncer durante o seguimento, quando comparadas às não tabagistas (p=0,04). Conclusões: O tabagismo, no passado ou presente, esteve associado a maior prevalência de infecção por HPV de alto risco oncogênico. O tabagismo também esteve associado ao aumento de risco de desenvolvimento de NIC 2 ou pior em mulheres com infecção por HPV de alto risco oncogênico. O tabagismo aumenta o risco de desenvolvimento de NIC2 ou pior em mulheres com citologia ASC/LSIL e colposcopia normal, em um período de 36 meses
Abstract: Objective: To assess whether smoking history interferes with the prevalence of hr-HPV infection and cervical intraepithelial neoplasia (CIN) and to prospectively examine the acquisition of hr-HPV infection and the development of CIN in baseline normal women. Subjects and methods: The study examines the baseline data on 12,114 women included in the Latin American Screening (LAMS) Study in São Paulo, Campinas, Porto Alegre and Buenos Aires, and the prospective data from 1,011 women, that included women with at least one positive test at baseline and no histological lesion and 10% of the women with normal cytology; and 150 women with ASC/LSIL and normal colposcopy at baseline, followed-up for a period of 36 months. Three groups were formed: 1) women that never smoked (n=7.499), 2) current (n=2.706) and 3) past smokers (n=1.871). The baseline assessment included the relation between the smoking history and several other epidemiological factors with the prevalence of hr-HPV infection and CIN. In the prospective analysis, women were controlled at 6-month intervals with colposcopy, HC2 and Pap to assess the cumulative risk of incident hr-HPV infection, smear abnormalities and CIN over a period of 36 months. Results: The most important significant differences were the higher prevalence (21.7%) of HR-HPV infections among current smokers as compared to women who never smoked (16.5%) or those smoking in the past (13.5%). Testing HR-HPV positive at baseline (OR=9.69; 95%CI=5-18.79), high-grade squamous intraepithelial lesion in baseline Pap smear (OR=40.52; 95%CI = 8.52-192.6) and history of no previous Pap smear (OR=2.65; 95%CI=1.21-5.79) were significant predictors of baseline CIN2 or worse. Among women with baseline abnormal Pap, progression to CIN2or or worse was substantially more frequent in current (5.8%) and past smokers (4.8%) than in never smokers (1.7%). During follow-up, testing HR-HPV+ at baseline significantly increased the risk of incident abnormal Pap, irrespective of the smoking status. Being a current smoker was a significant predictor of incident HR-HPV during the follow-up (HR =1.44; 95%CI 1.03-2.04), and, baseline HR-HPV+ (HR=10.07; 95%CI 1.32-76.49), being a past smoker (HR=3.61; 95%CI 1.06-12.33) and current smoker (HR=3.51; 95%CI 1.21-10.14) for incident CIN2 or worse. Among women with ASC/LSIL at baseline, the HR-HPV+ (HR = 3.42; 95%CI 1.11 to 9.43) was the only factor related to an increased risk of developing CIN during the 36-month followup. While restricting the analysis to high-grade CIN, the probability of developing the disease was significantly higher for smokers (p= 0.04). Conclusion: The smoking history, past or current, was related to a higher prevalence of HR-HPV, and to a increased risk of developing CIN2 or worse in women with HR-HPV+. Being smoker was related to a higher risk of developing CIN2 or worse in women with baseline ASC/LSIL and normal colposcopy, during 36-months follow-u
Doutorado
Tocoginecologia
Doutor em Tocoginecologia
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Bigrigg, Margaret Alison. "The use of large loop excision of the transformation zone for the treatment of cervical intraepithelial neoplasia." Thesis, University of Southampton, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.238899.
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Xi, Long Fu. "Genomic variation of human papillomavirus type 16 in relation to risk for high grade cervical and anal intraepithelial neoplasia /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/10887.
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Chevarie-Davis, Myriam. "Long term predictive values of cervical cytology and Human Papillomavirus DNA testing for the development of biopsy proven high grade cervical intraepithelial neoplasia." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107631.
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Cancer of the uterine cervix remains a significant cause of morbidity and mortality, even though it can be prevented by judiciously designed screening programs. Although many studies have compared Human Papillomavirus (HPV) DNA testing to cervical cytology, most of them have used cytology as an endpoint, thus being subject to outcome misclassification, or did not extend long enough to provide long term data. The aims of this project were to use the cervical cytology and HPV DNA test results performed in the context of a longitudinal cohort of over 10 years with repeated measurements to perform risk stratification for the development of cervical lesions confirmed by histology, the gold standard, and to compare the accuracy of both tests in the long term context. A cohort study of the natural history of HPV infection and cervical neoplasia was conducted in Brazil and enrolled 2462 women for questionnaire-based interviews and cervical screening according to a pre-established protocol. Whenever high-grade lesions were detected, subjects were referred for colposcopy and biopsy. Risk stratification was performed according to screening result, and the specificity, sensitivity and predictive values of HPV DNA testing and cytology were calculated. In addition, time-to-event analyses using Kaplan-Meier plots and Cox regression were performed. Low and high grade squamous intraepithelial lesions (SIL) on cytology, as well as the presence of high risk HPV DNA, all independently predicted high grade cervical lesions on biopsy in both the short and long term. When combined, the addition of HPV DNA testing to cytology was beneficial in cases of atypical smears, but not SIL. The long term negative predictive values were equivalent for negative cytology smears and negative HPV DNA tests. Dual testing with cytology and HPV DNA testing provided the best sensitivity and specificity over single modalities and other combinations.Elucidation of the performance and ideal use of screening tests in differing contexts contributes to our knowledge on cervical cancer screening, and allow us to develop optimal recommendations.Le cancer du col de l'utérus demeure une cause significative de morbidité et de mortalité, malgré qu'elle puisse être prévenue par des programmes de dépistage bien conçus. Quoique de nombreuses études ont comparé le test de dépistage du virus du papillome humain (VPH) et la cytologie cervicale, plusieurs ont utilisé la cytologie comme résultat, devenant par le fait même susceptible de souffrir d'une classification erronée, et d'autres n'ont pas duré suffisamment longtemps pour recueillir des données à long terme. Les buts de ce projet étaient d'employer les résultats de cytologie et du test de VPH obtenus dans le contexte d'une étude de cohorte longitudinale s'étendant au delà de 10 ans afin de stratifier les risques de lésions cervicales tel que confirmé par histologie et de comparer les deux tests à long terme.Une étude de cohorte portant sur l'histoire naturelle des infections à VPH et sur les néoplasies cervicales a eu lieu au Brésil, recrutant 2462 femmes pour des entrevues et des tests de dépistages selon un protocole préétabli. Les participantes étaient référées en colposcopie dès qu'elles étaient diagnostiquées avec une lésion de haut grade. La stratification des risques a été complétée selon les résultats au dépistage, et la spécificité, sensibilité et les valeurs prédictives des tests utilisés ont été calculées. Les lésions intra épithéliales cervicales (LIC) de bas et de haut grades, ainsi que la détection de VPH de haut risque, ont tous prédit la présence de lésions cervicales de haut grade tant à cours terme qu'à long terme. L'ajout du test de dépistage du VPH à la cytologie était bénéfique dans les cas de résultats atypiques, mais pas pour les LIC. La valeur prédictive négative à long terme était équivalente pour les cytologies négatives et pour les tests de VPH négatifs. La combinaison des deux tests offrait la meilleure sensibilité et spécificité par rapport aux tests individuels ou à toute autre combinaison. Les découvertes portants sur la performance et l'utilisation idéale des tests de dépistages dans des contextes variés contribuent aux connaissances sur le dépistage du cancer du col de l'utérus, et nous permettent de développer des recommandations optimales.
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Evander, Magnus. "Detection of human papillomavirus : a study of normal cells, cervical intraepithelial neoplasia and cancer of the uterine cervix." Doctoral thesis, Umeå universitet, Virologi, 1991. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-101351.
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Human papillomavirus (HPV) infections of the genital tract are now recognized to be among the most prevalent sexually transmitted diseases and also a contributing factor to some cancers of the lower genital tract of women and men. Presence of HPV in a clinical specimen is confined to detection of the HPV genome by DNA hybridization techniques. In this thesis, the commonly used DNA hybridization techniques Southern blot and filter in situ hybridization (FISH), were first used for detection of genital HPV infection. In order to increase and simplify the detection of HPV in clinical specimens a more sensitive technique, the polymerase chain reaction (PCR) was subsequently utilized. For type-specific amplificaiton of HPV 6, 16, 18 and 33 by PCR, oligonucleotide primers located in the E6 and E7 regions of the HPV genome were selected. They were found to specifically amplify the four types. To be able to amplify a broad spectrum of genital HPV types, general primers located in the E7 and El region of the HPV genome, were designed and evaluated. They were found to amplify a wide range of genital HPV types. To further increase the sensitivity and specificity, a two-step PCR using general primers, was assembled and evaluated against a one-step PCR on cervical scrapes from young women in a population-based study. The two-step PCR increased the sensitivity about three-fold compared to the one-step PCR. By Southern blot and FISH, 46% of women with abnormal Papanicolaou (Pap) smears were shown to carry HPV DNA. Of the women analysed by Southern blot, 39 % harboured HPV DNA and 25 % proved HPV 16 positive. Of the samples analysed with FISH, 27 % contained HPV DNA, compared to 11 % of samples from a group of reference women with normal cytology. With the Southern blot technique, HPV DNA was detected in 66% of women with cervical intraepithelial neoplasia grade III (CIN III) lesions. Fifty-four percent of the women with CIN III lesions were positive for HPV 16 DNA. By type-specific PCR, 12 out of 13 women with cervical squamous carcinoma were shown to carry HPV 16 and/or 18. Among women with adenosquamous carcinoma of the cervix, HPV 18 was the most prevalent type (26%) but HPV 16 was also found in a proportion of the women(15 %). Nine of 13 premenopausal cases with cervical adenocarcinoma were HPV positive compared to only 2 of 13 postmenopausal cases (p< 0.015). HPV 16 DNA was detected in 48%of women with cervical intraepithelial neoplasia (CIN), by the use of type-specific PCR. Three different groups of women with normal cytology were studied. Among women attending a family planning clinic in Kenya, 19% were shown to carry HPV virus, by the use of general primers. HPV 16 was found in 5.2% of these women and HPV 18 in 3.9%. In anothergroup of women, attending the gynecological department in Umeå, HPV 16 DNA was detected in 21 % by type-specific PCR. However, if consideration was taken to the medical status of the women, only 10% of women without any medical history were HPV 16 DNA positive, versus 54% of women with diseases and women with a relative progesterone dominance. Finally, by use of a two-step PCR using general primers, 20% of young women from Umeå taking part in a population-based study were demonstrated to carry HPV DNA. The most prevalent types were HPV 6 (2.0%) and HPV 16(2.7%). Among the women in this study with normal cytology, 19%were HPV positive.Diss. (sammanfattning) Umeå : Umeå universitet, 1991, härtill 9 uppsatser.
digitalisering@umu
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Veiga, Fernanda Rangel da. "Prevalência de lesão intra-epitelial escamosa de alto de alto grau e câncer cervical em pacientes com colpocitologia oncótica sugestiva de alto grau e colposcopia insatisfatória sem lesão visível." Instituto Fernandes Figueira, 2008. https://www.arca.fiocruz.br/handle/icict/8143.
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Previous issue date: 2008Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Departamento de Ensino. Programa de Pós-Graduação em Saúde da Criança e da Mulher. Rio de Janeiro, RJ, Brasil.
Introdução: O câncer de colo uterino ainda é considerado um grave problema de saúde pública no Brasil. Algumas recomendações para o controle desta doença no país são baseados em opiniões de especialistas e, no caso de pacientes com colpocitologias sugestivas de lesão intra-epitelial escamosa de alto grau (HSIL) e colposcopia insatisfatória sem lesão visível, consistem em repetir a colpocitologia após três meses. No Setor de Patologia Cervical do Instituto Fernandes Figueira/ FIOCRUZ, estas pacientes são encaminhadas diretamente para conização, na intenção de confirmar o diagnóstico e, caso presente HSIL, já se constituir no tratamento destas lesões. Objetivo: Medir a prevalência de HSIL e câncer em pacientes com a primeira colpocitologia sugestiva de HSIL e colposcopia insatisfatória sem lesão visível, além de identificar uma faixa etária ou grupos em que esta prevalência seja maior, no intuito de contribuir para a discussão sobre uma conduta clínica mais efetiva e que diminua a probabilidade de ocorrência de perdas antes do diagnóstico e tratamento adequados nesta situação. Material e método: Estudo transversal realizado através de pesquisa em banco de dados de pacientes recebidas no Setor de Patologia Cervical no período de dezembro de 1989 a abril de 2007 referidas pela rede básica de saúde para colposcopia, obtendo o diagnóstico final através dos laudos histopatológicos das peças de conização. Resultados: Foram incluídas 65 pacientes na situação descrita e encontrado percentual de 33,8% (IC95% 23,1- 45,9%) de HSIL e 4,6% (IC95% 1,1- 12,0%) de câncer confirmados histologicamente. Os demais casos apresentaram lesão intra-epitelial escamosa de baixo grau (LSIL - 26,1%, IC95% 16,5- 37,8%), displasia glandular (1,5%, IC95% 0,07- 7,35%) vii e ausência de doença (33,8%, IC95% 23,1- 45,9%). Não foi encontrada diferença estatisticamente significativa na razão de prevalência de HSIL e câncer em grupos de mulheres segundo estratos de idade abaixo e acima de 45 anos e entre mulheres soropositivas e soronegativas para HIV. Conclusão: A prevalência de HSIL ou câncer encontrada não parece suficiente para defender a conduta de encaminhá-las de imediato para conização a fim de investigar o canal cervical. Porém, são necessários ensaios clínicos randomizados para que possamos saber qual a conduta mais adequada na situação em estudo.
Introduction: Cervix cancer is a serious public health problem in Brazil. Some of the recommendations for controlling the disease in the country are based on the opinion of specialists. In patients with unsatisfactory colposcopy with no visible lesion and cervical cytology suggesting high-grade squammous intraepithelial lesion (HSIL), the recommendation is to repeat cervical cytology after three months. In the Cervical Pathology unit at Instituto Fernandes Figueira/ FIOCRUZ, these patients are directly subjected to conization in order to confirm diagnosis and to excise the lesions found, if HSIL is verified. Objectives: To assess prevalence of HSIL and cancer in patients with unsatisfactory colposcopy with no visible lesion and first cervical cytology suggestive of HSIL, and to identify an age group or other groups with higher prevalence in order to contribute to the discussion about a more effective clinical approach that will also prevent patients from abandoning follow-up before full diagnosis and treatment. Method: Cross-sectional study with data from the Cervical Pathology unit database on patients treated between December 1989 and April 2007 who were referred to the unit for colposcopy by the primary healthcare network. Final diagnosis was obtained through histopathological examination of conization specimens. Results: Of the 65 patients studied, 33,8% (CI95% 23,1- 45,9%) had HSIL, and 4,6% (CI95% 1,1- 12,0%) had cancer confirmed by histological examination. The other patients were diagnosed as having low-grade squammous intraepithelial lesion (LSIL - 26,1%, CI95% 16,5- 37,8%), glandular dysplasia (1,5%, CI95% 0,07- 7,35%), and absence of disease (33,8%, CI95% 23,1- 45,9%). This study did not find statistically significant ix difference of the prevalence ratio of HSIL and cancer between age groups of more than 45 and less than 45 years of age, and between women tested positive or negative for HIV. Conclusion: The prevalence of cancer and HSIL found in this study does not seem to be enough to justify direct referral for conization to investigate the cervical canal. Nevertheless, randomized clinical trials are necessary to determine an approach that would be more adequate in this situation.
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Cytryn, Andréa. "Risco de lesão intra-epitelial escamosa de alto grau e câncer cervical nas pacientes com diagnóstico citológico de células escamosas atípicas, quando não se pode excluir lesão intra-epitelial de alto grau." reponame:Repositório Institucional da FIOCRUZ, 2008. https://www.arca.fiocruz.br/handle/icict/3606.
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Previous issue date: 2008Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Departamento de Ensino. Programa de Pós-Graduação em Saúde da Criança e da Mulher. Rio de Janeiro, RJ, Brasil
A classificação citológica cérvico-vaginal mais atualizada, e que tem sido empregada em quase todo o mundo, é a do Sistema Bethesda. Sua última atualização, em 2001, subdividiu a categoria de células escamosas atípicas de significado indeterminado (Atypical Squamous Cells of Undetermined Significance – ASCUS) em ASC-US (de significado indeterminado) e ASC-H (quando não se pode excluir lesão intra-epitelial de alto grau), na qual espera-se maior probabilidade de se encontrar lesão precursora do câncer do colo. No Brasil, esta subdivisão foi adotada oficialmente pelo SUS (Sistema Único de Saúde) em junho de 2006, fazendo parte da Nomenclatura Brasileira para Laudos Citopatológicos. Esta pesquisa tem por objetivo medir a prevalência de lesão intra-epitelial escamosa de alto grau e câncer cervical em pacientes encaminhadas do SUS com citologia ASC-H, e comparar o risco desta lesão nas subcategorias de células escamosas atípicas (Atypical Squamous Cells - ASC) através do cálculo da Razão de Prevalências. Sua metodologia é baseada em casos com citologias ASCUS do SITEC (Sistema Integrado de Tecnologia em Citopatologia) recebidos no IFF (Instituto Fernandes Figueira) no período de agosto de 1998 a setembro de 2007, que foram revisados de acordo com o Sistema Bethesda 2001 até que se chegasse a um diagnóstico de consenso. Os casos ASC-H e ASC-US resultantes desta revisão, bem como os casos novos recebidos a partir de 2004, foram incluídos e analisados em relação ao desfecho. Para esta análise, incluíram-se os casos com diagnóstico histológico. Nos casos sem histologia, a colposcopia e a citologia foram consideradas como padrão-ouro. A prevalência da lesão de alto grau na citologia ASC-H foi de 19,29% (IC 95% 9,05 – 29,55%) e a possibilidade de doença de alto grau foi maior entre as pacientes com citologia ASC-H comparado às pacientes com citologia ASC-US (RP = 10,42 ICvii 95% 2,39 – 45,47) p = 0,0000764. Encontrou-se lesão de alto grau com maior freqüência nas pacientes abaixo dos 50 anos (RP = 2,67 IC 95% 0,38 – 18,83) porém sem significância estatística (p = 0,2786998). Não foram encontrados casos de câncer do colo do útero. A prevalência de lesão de alto grau em pacientes com citologia ASC-H foi significativa e a divisão em subcategorias do diagnóstico ASC se mostrou com boa capacidade para discriminar a presença de lesões de alto grau.
The Bethesda System is the most recent cervical and vaginal citopathology classification used almost worldwide. The Bethesda System’s last revision (2001) subdivided the category of Atypical Squamous Cells of Undetermined Significance (ASCUS) in ASC-US (of undetermined significance) and ASC-H (cannot exclude highgrade intraepithelial lesion), the last one carrying greater probability of finding precursors lesions of cervical cancer. This subdivision was adopted oficially by Brasilian Public Health System (SUS) in June 2006, becoming part of the Brasilian Nomenclature for Citopathological Reports. The aim of the study was measure the prevalence of High-grade Squamous Intraepithelial Lesion (HSIL) and cervical cancer, in patients whit citology of ASC-H and compare the risk of HSIL in the subcategories of ASC-H and ASC-US by Prevalence Ratio. The metodology was based in cases with citology ASCUS from SITEC (Integrated System of Tecnology in Citopatology) received in IFF (Fernandes Figueira Institute) from August 1998 to September 2007. The cytologies were reviwed by Bethesda System 2001 until a consensus diagnostic. The resultant cases of ASC-H and ASC-US from this review and the new cases recived from 2004, were included and analysed in relation to final diagnostic. This analysis included histology (gold standard) and those cases without histology, citology and colposcopy were the gold standard. We found 19,29% (CI 95% 9,05 – 29,55%) of prevalence of HSIL in ASC-H citology and the possibility of HSIL was greater in ASC-H cytology than in ASC-US (PR= 10,42, CI 95% 2,39 – 45,47%). We did not find cervical cancer. The prevalence of high-grade intraepithelial lesion in patients with ASC-H citology was significant and the subdivision of ASC (Atypical Squamous Cells) was good in discriminating the presence of HSIL.
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Westin, Maria Cristina do Amaral 1949. "Celulas glandulares atipicas e adenocarcinoma "in situ" de acordo com a classificação de Bethesda 2001 : associação cito-histologica." [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310570.
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Orientadores: Luiz Carlos Zeferino, Silvia Helena Rabelo dos SantosDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Introdução: Há evidências de que a incidência do adenocarcinoma do colo do útero tem aumentado, apesar dos programas de rastreamento. Foi a classificação do Sistema de Bethesda, em 1988, que incluiu o diagnóstico citológico relativo às células glandulares atípicas, que não estava presente nas classificações anteriores. Em sua revisão de 2001, o Sistema de Bethesda propôs a subclassificação do diagnóstico citológico de Anormalidades em Células Glandulares em: células glandulares atípicas sem outras especificações (AGC-SOE), células glandulares atípicas favorecendo neoplasia (AGC-FN) e adenocarcinoma in situ (AIS). Os diagnósticos citológicos de AGC constituem um problema clínico em consequência da falta de critérios citomorfológicos bem definidos para sua interpretação, do alto grau de variabilidade interobservador e da falta de achados colposcópicos característicos. O diagnóstico citológico de AIS, embora preditivo de neoplasia glandular, não pode diferenciar de modo preciso entre as formas in situ e invasiva, as quais só podem ser confirmadas pela histologia. Há, na literatura, divergentes opiniões quanto à utilidade desta subclassificação e sua análise é de grande relevância para prática clínica. Objetivo: Analisar a associação entre a classificação citológica do Sistema de Bethesda 2001 para as anormalidades do epitélio glandular cervical e o resultado histológico. Métodos: O estudo foi do tipo corte transversal analítico, prospectivo, realizado no Centro de Atenção Integral à Saúde da Mulher (CAISM), UNICAMP, entre 2002 e 2005, e incluiu uma série consecutiva de 155 mulheres com anormalidades glandulares endocervicais no exame citológico. Destas, 91 mulheres foram incluídas por AGC-SOE, 15 por AGC-FN; 14 por AIS e 35 por diagnóstico combinado de AGC associada à lesão escamosa intraepitelial de alto grau (HSIL). Os diagnósticos de AGC e AIS foram confirmados por dois observadores, de acordo com Sistema de Bethesda 2001. As mulheres com alterações glandulares,de origens outras que não endocervical, não foram incluídas no estudo. No primeiro atendimento foi colhido um segundo esfregaço cervical e realizada colposcopia em todas as mulheres. Foi realizada biópsia ou conização naquelas pacientes que tinham indicação, de acordo com a rotina assistencial do serviço. Todas as mulheres incluídas foram submetidas à ecografia pélvica. A magnitude da associação entre o diagnóstico citológico das anormalidades glandulares e o diagnóstico histológico foi estimada utilizando-se Odds ratio (OR), com respectivo intervalo de confiança (IC) de 95%. Resultados: Das 155 mulheres admitidas no estudo, 126 tiveram avaliação histológica. Tomando-se como referência AGC-SOE, os diagnósticos citológicos de AGC-FN e AIS foram significativamente associados com os resultados histológicos de neoplasia escamosa (NIC 2 ou pior diagnóstico) ou adenocarcinoma (in situ ou invasivo) com valores de odds ratio respectivamente de 10,50 (95% IC: 2,94- 37,55) e 156,00 (95% IC: 17,72-1373,46). Tomando-se como referência AGC-FN, o diagnóstico citológico de AIS foi significativamente associado com os resultados histológicos de neoplasia escamosa ou adenocarcinoma (OR=14,86; 95% IC: 1,53-144,23). Uma associação similar foi observada considerando-se os resultados histológicos de adenocarcinoma (in situ ou invasivo). Nenhuma associação foi observada para neoplasia escamosa analisada isoladamente. Os resultados histológicos de NIC 2 ou pior diagnóstico foram fortemente associados com AGC quando a lesão de alto grau (HSIL) também estava presente (OR=57,60; 95%IC: 18,25-181,76), mas nenhuma associação foi observada com resultado histológico de adenocarcinoma. Conclusões: Há uma associação significante entre as subclassificações da categoria de anormalidades em células glandulares de origem endocervical, propostas pelo Sistema de Bethesda 2001, e diagnósticos histológicos significativos, pois os diagnósticos citológicos de AGC-SOE, AGC-FN e AIS indicam um aumento progressivo de risco para adenocarcinoma. A presença de HSIL associada à AGC representa maior probabilidade de neoplasia escamosa, mas não de adenocarcinoma
Abstract: Introduction: There is evidence indicating that incidence of cervical adenocarcinoma has been increasing, despite the screening programs. The cytological diagnosis of atypical glandular cells, absent from previous versions, was included in the 1988 edition of the Bethesda System (TBS). In its review of 2001, the TBS has proposed the sub-classification of the cytological diagnosis of glandular cells abnormalities as: atypical glandular cells not otherwise specified (AGC-NOS), atypical glandular cells favor neoplastic (AGC-FN) and adenocarcinoma in situ "(AIS). The usefulness of the sub-classification of cytological diagnosis as atypical glandular cells not otherwise specified (AGC-NOS), atypical glandular cells favor neoplastic (AGC-FN) and adenocarcinoma in situ (AIS), as proposed in the 2001 TBS, is a controversial issue, but of great importance in clinical practice. AGC in cervical smears constitutes a clinical problem due to the lack of well-defined cytomorphological criteria for the interpretation of this finding, the high degree of interobserver variability and the lack of characteristic colposcopic features. Moreover, cytological AIS cannot specifically differentiate between AIS and invasive adenocarcinoma, which can only be confirmed by histology. Objective: to analyze the association between the 2001 TBS classification of glandular abnormalities and the histological outcome. Method: This cross-sectional and prospective study was conducted at the Center of Health Care of Women (CAISM), UNICAMP, between 2002 and 2005. The sample comprises a series of 155 women with glandular abnormalities in cervical smear. Of those, 91 women were included due to AGC-SOE, 15 due to AGC-FN, 14 due to AIS and 35 for AGC combined with high grade squamous intraepithelial lesions (HSIL). The diagnoses of AGC and AIS were confirmed by two observers according to the TBS 2001. Women with changes of glandular origin other than endocervical were excluded. In their first visit, a second cervical sample was collected from all women, and colposcopy was performed. A biopsy or a conization was performed when necessary, according to CAISM's protocols. All women underwent pelvic ultrassonography. Odds ratios (OR) with 95% confidence interval (95% CI) were used to evaluate the magnitude of the association between the cytological diagnosis of the glandular abnormalities and the significant histologic diagnosis. Results: Of the 155 women admitted to the study, 126 were submitted to histological examination. Taking as reference AGC-NOS, the cytological diagnosis of AGC-FN and AIS were significantly associated with the histological outcome of squamous neoplasia (CIN or worse) or adenocarcinoma (in situ or invasive) with OR values of 10.50 (95% CI: 2.94-37.55) and 156.00 (95% CI: 17.72-1373.46), respectively. Taking as reference AGC-FN, the cytological diagnosis of AIS was significantly associated with the histological outcome of squamous neoplasia or adenocarcinoma (OR=14.86; 95%CI: 1.53-144.23). Similar associations were observed for the histological outcome of adenocarcinoma, but no association was observed for only squamous neoplasia. Histological outcome of CIN2 or worse was strongly associated with AGC when HSIL was also present (OR = 57.60; 95% CI: 18.25- 181.76), but no association was observed with adenocarcinoma as the stand-alone histological outcome. Conclusions: There is an association between the subclassification of glandular cells abnormalities of endocervical origin proposed by 2001 TBS with significant histological outcomes. The cytological diagnoses of AGC-NOS, AGC-FN and AIS were progressively associated with adenocarcinoma. The histological outcome of squamous neoplasia is frequent but does not differ from these cytological interpretations. The presence of HSIL associated with AGC was associated with a greater probability of squamous neoplasia, but not
Mestrado
Ciencias Biomedicas
Mestre em Tocoginecologia
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Monteiro, Junior Orlando [UNESP]. "Neoplasia intra-epitelial cervical em mulheres soro-positivas para o vírus da imunodeficiência humana." Universidade Estadual Paulista (UNESP), 2001. http://hdl.handle.net/11449/93112.
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monteirojunior_o_me_botfm.pdf: 372086 bytes, checksum: e70c404b57dbf716ae6468fc47c63be9 (MD5)Objetivando estudar a prevalência de neoplasia intra-epitelial cervical (NIC) em mulheres soro-positivas para o vírus da imunodeficiência humana (HIV) ao compará-las com um grupo controle de mulheres soro-negativas, foi realizado um trabalho retrospectivo em que foram avaliadas 86 mulheres HIV positivas e 86 mulheres HIV negativas, que freqüentaram um serviço público de acompanhamento em DST/AIDS na cidade de Campo Grande, Mato Grosso do Sul, Brasil. Foram realizadas avaliações citológicas pelo Papanocolaou, colposcopias e biópsias quando indicadas. Encontrou-se uma prevalência maior de NIC no grupo de mulheres HIV positivas em comparação ao grupo de mulheres HIV negativas, e esta diferença foi estatisticamente significativa. Conclui o autor que, sendo o câncer do colo uterino uma patologia previnível e com o atual aumento da expectativa de vida das pacientes HIV positivas, este grupo de mulheres merece atenção ginecológica diferenciada com consultas mais frequentes e livre acesso à colposcopia.
Objetiving to study the prevalence of cervical intraepithelial neoplasia (CIN) in human immunodeficiency virus (HIV) – infected women and to compar with a group control of seronegative women, it was realized a retrospective study being assessed 86 HIV – infected and 86 HIV – unifected women, who were attended in a public service of accompaniment in TSD/AIDS in Campo Grande City, Mato Grosso do Sul, Brazil. Were realized evolution cytologic for the Papanicolaou test, colposcopy and biopsies, when indicated. It was found a prevalence of CIN significantly greater in HIV – seropositive women than in seronegative women. In conclusion, being the cervical cancer a pathology that can be prevented and with the current increase of the life’s expectative of the HIV – seropositive women, this group of women needs a better gynecologic atenttion with visits and Papanicolaou smears more often and free access to colposcopy.
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Denny, Lynette Ann. "Does colposcopically directed punch biopsy reduce the incidence of negative LLetz?" Thesis, University of Cape Town, 1994. http://hdl.handle.net/11427/26241.
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Wang, Xiuli. "Pharmacokinetics and Selectivity of ALA-induced Porphyrin Synthesis after Topical Application of Hexyl-Aminolevulinic-Acid in Cervical Intraepithelial Neoplasia." Diss., lmu, 2004. http://nbn-resolving.de/urn:nbn:de:bvb:19-26566.
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Bastos, Joana Fróes Bragança 1971. "Expressão do 'p16 POT. INK4a' e do p53 como marcadores prognosticos da neoplasia intra-epitelial cervical e sua relação com o papilomavirus humano de alto risco oncogenico." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312148.
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Orientadores: Sophie Françoise Mauricette Derchain, Luis Otavio Zanatta SarianTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Objetivo: Avaliar a relação da expressão do p53 e do p16INK4a em diferentes graus de neoplasia intra-epitelial cervical (NIC) e suas possíveis relações com a recidiva/persistência da NIC após conização diatérmica e a infecção persistente de papilomavírus humano (HPV) de alto risco oncogênico. Sujeitos e métodos: Este foi um estudo de corte, com análise intermediária em corte transversal, para o qual foram selecionadas mulheres submetidas à conização diatérmica no período de fevereiro de 2001 a abril de 2004. Os resultados deste estudo são apresentados em dois artigos: o primeiro consiste em corte transversal incluindo 125 espécimes cirúrgicos de mulheres submetidas a conização diatérmica. Foram avaliadas a expressão do p53 e do p16INK4a em diferentes graus de NIC e sua relação com a infecção pelo HPV de alto risco oncogênico realizado através da Captura de Híbridos 2 (CH2). No segundo artigo, com análise longitudinal foram incluídas 104 mulheres com NIC 2 ou 3, seguidas por até 24 meses após conização diatérmica. Foram avaliadas a expressão de p16INK4a e p53 como fatores préditivos de persistência/recidiva de NIC e a sua relação com a infecção persistente por HPV de alto risco oncogênico após o conização cervical diatérmica. Resultados: No primeiro artigo foram incluídos 21 casos cervicites/NIC1, 17 NIC2 e 87 NIC3. Noventa e nove (79,2%) casos foram positivos para p16INK4a (> 5% do epitélio corado), significativamente maior em lesões de alto grau (p< 0.001). A expressão do p53 não variou de acordo com o grau histológico. Não houve correlação entre a expressão da p16INK4a e a detecção do HPV de alto risco oncogênico. A expressão do p16INK4a não teve relação com a do p53. No segundo artigo, 104 mulheres com NIC 2 ou 3 foram acompanhadas por 24 meses, e detectou-se 12 casos de recidiva/persistência de NIC, sendo 8 nos primeiros 6 meses. Entre as mulheres com recidiva/persistência de NIC, 9 (75%) apresentaram presistência do HPV de alto risco oncogênico. A expressão da p16INK4a foi moderada/forte em 96 casos (92%) e mais de 50% dos núcleos estavam corados para p53 em 80 (78%). A análise prospectiva não detectou diferença significativa na recidiva/persistência da NIC durante o follow up com segundo a expressão do p16INK4a ou do p53. Nenhum dos parametros estudados teve relação com a infecção persistente pelo HPV. Conclusões: este estudo está em concordância com o conhecimento atual e mostra uma associação da positividade para p16INK4a com a severidade da lesão cervical, embora esta proteína não esteja associada com a detecção de HPV de alto risco oncogênico pela CH2. Não houve correlação entre a expressão de p53 e a positividade para HPV nem houve associação da expressão do p53 com a do p16INK4a. A análise prospectiva não mostrou correlação entre a expressão do p 16 INK4a e do p53 e a recorrência/persistência da NIC ou persistência do HPV de alto risco oncogênico no seguimento de mulheres com NIC 2 ou 3 tratadas com conização diatérmica
Abstract: Objective: to concurrently investigate the immunoexpression of p53 and p16INK4a4 in different grades of cervical intra-epithelial neoplasia (CIN) and their relation with the persistence/ recurrence of CIN and persistent infection by high-risk Human Papillomavirus (hr-HPV) after electrosurgical cervical conization. Subject and methods: a series of 125 women subjected to electrosurgical conization was selected for this cross-sectional and cohort study. Enrollment was carried out between February 2001 and April 2004. The results of this study are presented in two articles: the first one consists of a cross-sectional analisys, including 125 surgical specimens of women who underwent diathermic conization. Expression of p53 and p16INK4a were evaluated in different grades of CIN and their relation with hr-HPV infection was evaluated with HC2. The second article is a longitudinal analysis on 104 women with CIN 2 and 3, followed up for 24 months after electrosurgical cervical conization. Expression of p16INK4a and p53 were tested as predictive markers of persistent/recurrent CIN and persistent infection by hr-HPV during follow up after electrosurgical cervical conization. Results: in the first series, 21 cases of CIN1, 17 CIN2 and 87 CIN3 were included. Ninety-nine (79.2%) cases stained moderate/strongly to p16INK4a, significantly higher in high-grade CIN (p< 0.001). p53 expression did not relate with the grade of CIN and there was no relation between p16INK4a expression and hr-HPV detection. Expression p16INK4a and p53 were not correlated. In the second article, 104 women with CIN 2 or 3 were followed up for 24 months, and 12 (11%) persistent/recurrent CIN were observed, eight of them during the first 6 months follow-up. Among women with persistent/recurrent CIN, 9 (75%) presented persistent hr-HPV detection. p16INK4a expression was moderate/strong in 96 cases (92%) and p53 stained in more than 50% of the nuclei in 80 (77%). The expression of p16INK4a or p53 was not associated with persistent/recurrent CIN during follow-up. None of the studied parameters correlated with persistent hr-HPV detection. Conclusion: these results showed a strong association between p16INK4a expression and grade of CIN, although this protein was not associated with hr-HPV detection by HC2. There was no relation between p53 and hr-HPV detection or p16INK4a expression. Prospective analysis showed that p16INK4a and p53 expression was not related with persistent/recurrent CIN or persistent hr- HPV detection during follow-up of women conservatively treated for CIN 2 or 3
Doutorado
Tocoginecologia
Doutor em Tocoginecologia
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Resende, Leandro Santos de Araújo 1980. "Infecções simples e múltiplas por HPV em mulheres brasileiras de diferentes faixas etárias com lesões cervicais escamosas ou glandulares = Single and multiple HPV infections in Brazilian women of different age strata with squamous or glandular cervical lesions." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312153.
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Orientadores: Sophie Françoise Mauricette Derchain, Silvia Helena Rabelo dos SantosDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: O câncer do colo uterino é o terceiro tipo mais prevalente no mundo e representa a quarta causa de morte por câncer entre as mulheres. No Brasil, estima-se que 17,540 mulheres foram diagnosticadas com essa neoplasia no ano de 2012. A infecção persistente pelo Papillomavirus humano (HPV) de alto risco (hr-HPV) e é considerada fator causal e necessário para lesões precursoras e câncer invasor. Já foram identificados mais de 100 tipos de HPVs. Os HPVs 16 e 18 são reconhecidos, no mundo, como os maiores responsáveis pelo desenvolvimento dessa doença. Objetivos: Descrever a prevalência e a distribuição, por idade, de infecções simples e múltiplas por diferentes tipos de HPV em mulheres com lesões cervicais escamosas e glandulares. Sujeitos e métodos: 328 mulheres com lesões escamosas, ou glandulares intraepiteliais ou invasoras do colo uterino. Todas as amostras foram submetidas à genotipagem por hibridização reversa com sondas de 21 tipos de HPV de alto risco (hr-HPV) e 16 tipos de HPV de baixo risco (lr-HPV). A prevalência de infecções simples e múltiplas pelo HPV foi comparada de acordo com as faixas etárias. Resultados: 287 (87%) mulheres apresentaram infecção por pelo menos um tipo de HPV e 149 (52%) tinham infecção múltipla. O HPV16 foi o tipo de vírus mais prevalente na amostra, detectado em 142 casos (49% de todos os casos positivos para HPV), seguido dos outros tipos de HPV do grupo alfa-9: HPVs 58, 52, 31, 35 e 33. Infecção simples ou múltipla pelo HPV18 foi positiva em 23 casos (8% dos casos de infecção por HPV de alto risco). Praticamente todas as lesões glandulares foram associadas à infecção simples por HPVs 16 e 18. Infecções múltiplas foram, significativamente, mais prevalentes nas lesões escamosas do que nas glandulares pelos HPVs 16 e 18 (P=0,04 e 0,03, respectivamente). A prevalência de infecções múltiplas seguiu um modelo de distribuição bimodal, com pico em mulheres com menos de 29 anos e naquelas com idade entre 50 e 59 anos. Conclusão: Esta amostra sugere que a estratégia para prevenção de lesões pré-invasivas e invasivas, escamosas ou glandulares, deve ser direcionada para o HPV16 e alguns tipos virais do grupo alfa-9. Ficou claro, na amostra deste estudo, que em mulheres jovens, a prevenção de infecção pelo HPV deve cobrir os HPVs 16 e 18, principalmente
Abstract: Background: Cervical cancer ranks third in prevalence and fourth as cause of death in women worldwide. In Brazil, 17,540 women were diagnosed in 2012 with the disease. Persistent infection with high-risk HPV types is a necessary condition for the development of pre-invasive and invasive cervical neoplasia. Currently, over 100 HPV types have been identified, but HPV16 and 18 are recognized as the mayor culprits in cervical carcinogenesis. Objectives: to assess the relationships between single- (ST) and multiple-type (MT) HPV infection with patients' age and lesion pathological status. Materials and Methods: 328 patients with either squamous or glandular intraepithelial or invasive cervical lesion were selected. All subjects were tested for HPV genotypes with reverse hybridization for 21 high- (hr-HPV) and 16 low-risk (lr-HPV) probes. Prevalence of ST and MT HPV infections was compared across and age strata. Results: 287 (87%) women had at least one HPV type detected and 149 (52%) had MT infections. The most prevalent HPV type was HPV16, present in 142 cases (49% of all HPV-positive cases), followed by the alpha-9 group HPV58, 52, 31, 35 and 33, all of them from alpha-9 HPV group. ST or MT HPV18, single or in multiple infections occurred in 23 cases (8% of hr-HPV cases). Almost all glandular lesions were associated with HPV16 and 18 alone. Multiple infections were significantly more prevalent in squamous than in glandular lesion for HPV16 and 18 (P=0.04 and 0.03 respectively). The prevalence of MT infections followed a bimodal distribution; peaking in women younger 29 years and in those aged 50 to 59. Conclusions: our data indicate that prevention strategies for pre-invasive and invasive squamous lesions should be focused on HPV16 and a few alpha-9 HPV types. It is clear to us that in young women, prophylaxis must cover a large amalgam of HPV types beyond classic HPV16 and 18
Mestrado
Oncologia Ginecológica e Mamária
Mestre em Ciências da Saúde
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Fernández, Karla Lucía Alvarez. "Caracterização do infiltrado inflamatório no carcinoma cervical e em suas lesões precursoras." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-12092016-095657/.
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A história natural do câncer cervical invasivo começa com uma infecção produtiva pelo Papiloma vírus humana (HPV) na camada basal do epitélio. Infecções persistentes por vírus de HPVs de alto risco poderão provocar lesões que eventualmente darão origem ao carcinoma invasivo. Sabe-se que o infiltrado inflamatório pode ter um papel importante na evolução da doença. Neste trabalho, quantificamos e caracterizamos fenotipicamente linfócitos T, macrófagos e neutrófilos nas lesões precursoras assim como no carcinoma invasivo. Além disso, para determinar se existia alguma relação entre as populações foi realizada uma análise de correlação entres as populações descritas. Por outro lado, tentando determinar o efeito sistêmico do tumor avaliou-se a frequência de subtipos de monócitos circulantes e através de ensaios alogênicos foi avaliada a capacidade estimuladora das células dendríticas diferenciadas de monócitos circulantes. Os dados apresentados ajudarão a entender o papel que as células do sistema imune podem ter sobre a progressão da doença.The natural history of cervical cancer begins with a human papilloma virus (HPV) infection of the cells of the basal layer of the epithelium. Persistent infection by high risk HPVs can originate precancerous lesions that may progress to invasive cancer. It has been established the role of the infiltrated inflammatory cells on the progression of the disease. In this work, the phenotype and the frequency of T lymphocytes, macrophages and neutrophils were characterized both in precursor lesions as in invasive carcinoma. In order to stablish a possible relation between the characterized cells, we made a correlation analysis. On the other hand, trying to determine the systemic effect of the tumor we evaluated the frequency of circulating monocyte subtypes and the capacity of dendritic cells to stimulate allogeneic T cells. The data presented will help to understand the role of the immune system cells on the progression of the disease.
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Samir, Raghad. "Tissue tumor marker expression in normal cervical tissue and in cervical intraepithelial neoplasia, for women who are at high risk of human papilloma virus infection, are smokers, contraceptive users or in fertile age." Doctoral thesis, Uppsala universitet, Obstetrik & gynekologi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-262889.
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The aim of this research was to study the correlation between tissue tumor marker expression and HR-HPV infection, smoking, hormonal contraceptive use and sex steroids in women with cervical intraepithelial neoplasia or normal epithelium. The study investigated the expression of 11 tumor markers in cervical biopsies obtained from 228 women with different diagnoses ranging from normal cervical epithelium to various stages of CIN. 188 women were recruited at our colposcopy clinic (out-patient surgery, Department of Obstetrics and Gynecology, Falun Hospital) for laser cervical conization or a directed punch biopsy, either because of a vaginal smear (Pap smear) that showed cytological findings suggesting CIN, or because of repeated findings showing atypical squamous cells of undetermined significance (ASCUS). For 40 volunteers, punch biopsies were taken from the normal cervical epithelium. The time period for this study was 2005-2007. Study I : 228 women, of whom 116 were tested, 64 were positive to HR-HPV. The results showed that Ki67 tumor cell proliferation index was the only marker that independently correlated to both the presence of HR-HPV and the severity of cervical lesions. Study II: 228 women, of whom 83 were smokers (36, 9%). Smokers showed lower expression of p53, FHIT (tumor suppressor markers) and interleukin-10 .Higher expression of Cox-2 and Ki-67 (tumor proliferation markers). Study III: 195 women who were premenopausal. There was increased p53 expression (tumor suppressor) in the progestin-IUD users compared to non-users. Decreased IL-10 expression (immunological marker) was observed in both COC users and any progestin-only users. Study IV: Serum from 80 premenopausal women was available. The main finding was that the increased levels of serum progesterone and estradiol were associated with increased Cox-2 expression (proliferation marker). Serum progesterone and estradiol levels influence cellular and extracellular proteins which have been associated with neoplastic development in normal epithelium and CIN. Conclusion: The results of these studies support previous epidemiological findings on the role of smoking, contraceptive use and sex steroids as co-factors in development of CIN and that tumor marker expression varies in different grades of CIN.
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Klitzke, Sibele. "Alterações pré-malignas do colo uterino em pacientes transplantadas renais em um centro de referência do sul do Brasil." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/151016.
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Introdução: Pacientes transplantadas renais evoluíram para uma maior sobrevida e uma melhor função renal com o advento dos imunossupressores. A rejeição do enxerto deixou de ser a principal causa de morbimortalidade, e outros problemas crônicos surgiram, como infecções e neoplasias induzidas por vírus, como as lesões precursoras de câncer de colo uterino induzidas pelo Papilomavírus Humano (HPV). Objetivo: Avaliar a prevalência de alterações no exame citopatológico do colo do útero (CP) em pacientes transplantadas renais e compará-la à prevalência de alterações no CP em pacientes imunocompetentes. Método: Estudo transversal com grupo controle de alterações do CP em pacientes transplantadas renais e em pacientes imunocompetentes, no período de maio de 2015 a agosto de 2016. Resultados: A frequência de lesão intraepitelial de baixo (LIEBG) e alto grau (LIEAG) foi três vezes maior no grupo das transplantadas em relação ao grupo controle (20,6% no grupo transplantadas vs 6,8% no grupo controle, p<0,001) considerando todos os CPs coletados após o transplante. Na avaliação ginecológica ambulatorial no período do estudo não houve diferença entre os grupos em relação ao resultado "normal" e "alterado" do CP (resultado normal em 152 pacientes transplantadas (92,1%) vs 326 pacientes (93,9%) do grupo controle). Entretanto, quando se estratificaram os resultados alterados, evidenciou-se maior frequência de LIEBG nas transplantadas (3,6% vs 0,0%, P<0,001). Conclusão: O grupo de pacientes transplantadas renais apresentou uma taxa significativamente maior de alterações no CP em relação ao grupo controle, sendo que a maior parte foi composta de LIEBG.Introduction: Renal transplant recipients (RTR) evolved to greater survival and improved renal function with the advent of immunosuppressants. Graft rejection is no longer the leading cause of morbidity and mortality, and other chronic problems have arisen, such as virusinduced infections and neoplasms, such as HPV-induced precursor lesions of cervical cancer. Objective: To evaluate the prevalence of cervical pre-malignancies in the Pap smear (PS) in female RTR and compare to the prevalence of cervical pre-malignancies in the immunocompetent patients. Methods: Cross-sectional study with control group performed with 165 female RTR and 372 immunocompetent patients from May 2015 to August 2016. Results: This study observed a frequency 3 times higher of HSIL (CIN 2) and LSIL in the RTR group (20.6% of RTR vs. 6.8% in the control group) considering the Pap smears collected after the renal transplant. There was no difference between the groups regarding the "normal" and "altered" result from the PS in the outpatient gynecological evaluation (during the study). The exam had normal results in 152 RTR (92.1%) vs. 326 patients (93.9%) in the control group. However, when the altered results were broken down, a higher frequency of LSIL could be seen in RTR (3.6% vs 0.0%, P<0.001). Conclusion: RTR had a significantly higher rate of PS alterations in comparison with the control group and most of it was composed of LSIL.
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Arnheim, Lisen. "Immunological responses in genital HPV infections and etiology of cervical cancer /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-266-7/.
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Hawes, Stephen Edward. "HIV-1, HIV-2, and dual infection with HIV-1 and HIV-2 are associated with increased risk for human papillomavirus (HPV) and high grade squamous intraepithelial lesions (HSIL) in Senegal, West Africa /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/10881.
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Cremer, Miriam, Proma Paul, Katie Bergman, Michael Haas, Mauricio Maza, Albert Zevallos, Miguel Ossandon, Jillian D. Garai, and Jennifer L. Winkler. "A Non-Gas-Based Cryotherapy System for the Treatment of Cervical Intraepithelial Neoplasia: A Mixed-Methods Approach for Initial Development and Testing." US AGENCY INT DEVELOPMENT-USAID, 2017. http://hdl.handle.net/10150/624357.
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Background: Gas-based cryotherapy is the most widely used treatment strategy for cervical intraepithelial neoplasia (CIN) in low-resource settings, but reliance on gas presents challenges in low-and middle-income countries (LMICs). Our team adapted the original CryoPen Cryosurgical System, a cryotherapy device that does not require compressed gas and is powered by electricity, for use in LMICs. Methods: A mixed-methods approach was used involving both qualitative and quantitative methods. First, we used a user-centered design approach to identify priority features of the adapted device. U.S.-based and global potential users of the adapted CryoPen participated in discussion groups and a card sorting activity to rank 7 features of the adapted CryoPen: cost, durability, efficacy and safety, maintenance, no need for electricity, patient throughput, and portability. Mean and median rankings, overall rankings, and summary rankings by discussion group were generated. In addition, results of several quantitative tests were analyzed including bench testing to determine tip temperature and heat extraction capabilities; a pathology review of CIN grade 3 cases (N=107) to determine target depth of necrosis needed to achieve high efficacy; and a pilot study (N=5) investigating depth of necrosis achieved with the adapted device to assess efficacy. Results: Discussion groups revealed 4 priority themes for device development in addition to the need to ensure high efficacy and safety and low cost: improved portability, durability, ease of use, and potential for cure. Adaptions to the original CryoPen system included a single-core, single-tip model; rugged carrying case; custom circuit to allow car battery charging; and sterilization by high-level disinfection. In bench testing, there were no significant differences in tip temperature or heat extraction capability between the adapted CryoPen and the standard cryotherapy device. In 80% of the cases in the pilot study, the adapted CryoPen achieved the target depth of necrosis 3.5 mm established in the pathology review. Conclusion: The LMIC-adapted CryoPen overcomes barriers to standard gas-based cryotherapy by eliminating dependency on gas, increasing portability, and ensuring consistent freeze temperatures. Further testing and evaluation of the adapted CryoPen will be pursued to assess scalability and potential impact of this device in decreasing the cervical cancer burden in LMICs.
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Paes, Eliana Ferreira 1976. "Desenvolvimento de um teste biomolecular para detecção de HPV em amostras cervicouterinas : descrição do método e avaliação inicial." [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312780.
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Orientador: Júlio César TeixeiraDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: O agente etiológico do câncer do colo do útero é um HPV de alto risco (hrHPV) e testes biomoleculares para detecção deste vírus em amostras do colo do útero tendem a ter um papel cada vez mais importante no rastreamento de lesões pré-câncer para o futuro. No momento, estes testes são de alto custo e de execução complexa. Objetivo: desenvolver e padronizar um teste de PCR multiplex marcado com fluorescência para detecção de DNA de hrHPV em amostras obtidas do colo do útero e comparar com um teste de referência. Metodologia: foi realizado um estudo piloto para descrição e padronização de uma metodologia de detecção e genotipagem de HPV, tipo PCR multiplex, com primers desenhados com base na região E7 de seis hrHPV (16, 18, 31, 33, 45 e 52), o teste `E7-HPV¿. Foi seguido um guia internacional para desenvolvimento de novos testes de HPV para rastreamento, que orienta uma avaliação inicial de 50 ou mais amostras de mulheres com NIC2+, comparação com um teste referência validado, e alcançar um índice de concordância kappa de 0,7, com sensibilidade de 90% da sensibilidade do teste referência. O teste referência adotado foi o cobas® HPV Test da Roche Diagnostics, chamado `cobas®¿, que identifica em grupo 12 hrHPV e genotipa os tipos 16 e 18, separadamente. Neste estudo foram utilizadas amostras de 60 pacientes, 55 com citologia ASCH/HSIL, coletadas entre Agosto e Setembro de 2013, que foram avaliadas por cada teste com cálculo da concordância dos resultados pelo índice de kappa e comparação da sensibilidade, com poder estatístico de 90%. Resultados: o teste teve sua descrição e padronização finalizada. Houve alta concordância entre os testes `E7-HPV¿ e cobas® na detecção do HPV 16 com kappa 0,972, com apenas um caso discordante, de paciente com NIC3 com cobas® negativo e com o teste `E7-HPV¿ positivo. Para o HPV18, os resultados dos testes demonstraram concordância total, com índice kappa=1,0. Quando comparadas as detecções dos tipos hrHPV não 16 e 18, seis casos foram positivos para o cobas® e negativos para o teste `E7-HPV¿, podendo ser decorrente da detecção do cobas® de tipos de HPV não contemplados no teste `E7-HPV¿. Ao contrário, o teste `E7-HPV¿ detectou dois hrHPV adicionais, com cobas® negativo (HPV31 e 52). A sensibilidade de detecção de NIC2+ foi igual para os dois testes avaliados. Conclusão: Foi possível desenvolver e padronizar uma técnica de PCR multiplex com metodologia para detecção de seis hrHPV. O desempenho do teste `E7-HPV¿ foi, pelo menos, equivalente ao teste referência (cobas® HPV Test) com kappa=0,972 e 100% da sensibilidade do teste referência na detecção de NIC2+ em pacientes sabidamente com lesões, superando os pré-requisitos necessários. Assim, os resultados satisfatórios do `E7-HPV¿ na primeira fase de avaliação possibilita a continuidade do desenvolvimento do mesmo, visando futura aplicação em maior escala
Abstract: Introduction: the etiologic agent of cervical cancer is a high-risk HPV (hrHPV) and biomolecular tests for detection of this virus in cervical samples tend to have an increasingly important role in screening for precancerous lesions for the future. At present, these tests are expensive and complex procedure. Purpose: to develop and standardize a multiplex PCR test, 'E7-HPV' test, to detect and genotyping of 6 hr-HPV DNA, tested in samples obtained from the cervix and compared with a reference test. Methods: A pilot study was performed to develop and standardize a methodology of the multiplex PCR with primers designed on the basis of six hrHPV E7 region (16, 18, 31, 33, 45 and 52) and labeled with fluorochrome 6-FAM. Viral detection was performed by capillary electrophoresis in automated sequencer. It was followed an international guide to development of new HPV testing for screening, which guides an initial assessment of 50 or more samples from women with CIN2+, and the results compared to a validated reference test to achieve a kappa index of 0.7, and 90% sensitivity of reference sensitivity test. The reference test adopted was the cobas® HPV Test from Roche Diagnostics, called 'cobas®', which identifies 12 hrHPV pooled and genotype HPV 16 and 18 separately. In this study, cervix samples were obtained from 60 women, 55 with ASCH/HSIL cytology, collected between August to September 2013. The samples were evaluated by each test, and a non-inferiority analysis was conducted in relation to the cobas® HPV Test, following international guidelines for the development of new tests with kappa index and sensitivity, with a statistical power of 90%. Results: The methodology of E7-HPV test was described and standardized. The 'E7-HPV' test and cobas® Test had a high concordance rate in HPV16 detection (kappa=0.972), with only one discordant case (CIN3 with negative cobas® and `E7-HPV¿ HPV16 positive) and total concordance in HPV18 detection (kappa=1.0). When comparing the detection of hrHPV not 16/18, six cases were positive for cobas® and negative for 'E7-HPV', maybe due to the detection for cobas® of HPV types not included in the 'E7- HPV ' test. Others three cases were `E7-HPV¿ positive (HPV16, 31 and 52) with negative cobas®. For diagnosis of CIN2 or worse, both tests had the same sensitivity. Conclusion: It was possible to develop and standardize a multiplex PCR methodology for detection and genotyping 6 hrHPV in cervical samples. The performance of 'E7-HPV' test was at least equivalent to the reference test for the detection of CIN2+, fulfilling the clinical validation criteria requirements. Thus, the satisfactory initial results of the 'E7-HPV' test evaluation indicate that the development can be continued, aiming future application on a larger scale
Mestrado
Oncologia Ginecológica e Mamária
Mestra em Ciências da Saúde
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Miralpeix, Rovira Ester. "Valor predictiu de les cèl·lules NK en l’evolució de la neoplàsia intraepitelial cervical grau 2." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/393970.
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La Neoplàsia Intraepitelial Cervical (CIN) és una lesió precursora del càncer de cèrvix amb una història natural ben coneguda que s’inicia a partir de la infecció pel virus del papil·loma humà (VPH). Existeixen múltiples cofactors que poden modular la capacitat de regressió/progressió espontània la CIN. Malauradament encara que no es coneixen factors predictors clínicament útils per poder predir la seva evolució. El CIN2 és una entitat intermèdia entre el CIN1 i el CIN3 amb unes taxes de regressió espontània del 40-60% i de progressió del 10-20% descrites a la literatura. El maneig habitual de les lesions de CIN2 és la conització, però les actuals guies americanes (ASCCP) i Espanyoles (SEGO) proposen un maneig conservador i seguiment de les lesions de CIN2 en pacients joves i seleccionades, per evitar els efectes secundaris de la conització. Per tal de poder identificar marcadors que ens puguin predir l’evolució de les lesions de CIN2, es proposa estudiar el sistema immunitari, concretament les cèl·lules NK. Les cèl·lules NK es troben a sang perifèrica i tenen la capacitat d’eliminar cèl·lules tumorals o infectades les quals han perdut, en condicions patològiques, l’expressió de les molècules del Complex Major d’Histocompatibilitat de classe I (MHC I) que evitarien l’activació de la resposta immunològica de les cèl·lules T.
La hipòtesis de treball és que una pitjor funcionalitat de les cèl·lules NK, analitzada a través de un menor percentatge d’expressió de receptors de les cèl·lules NK, podria disminuir la capacitat de regressió espontània de les lesions de CIN2.
Entre desembre de 2011 i octubre de 2013 s’han inclòs les pacients amb diagnòstic histològic de CIN2, majors de 18 anys que acceptaven realitzar una maneig conservador amb controls cada 4 mesos durant 2 anys. La colposcòpia no satisfactòria i el tractament immunosupressor eren criteris d’exclusió. A totes les pacients s’han quantificat les cèl·lules NK, s’han estudiat les serologies (VIH, Herpes 2, VHB, VHC, Lues i Clamídia), la citologia prèvia al diagnòstic, el genotipat del VPH i els factors socio-demogràfics. La regressió total s’ha definit com la pacient que posterior a 2 anys presenta les 2 últmes citologies normals i no s’evidencia lesió colposcòpica, la regressió parcial si presenta biòpsia de CIN1, persistència biòpsia de CIN2 i progressió si en qualsevol moment durant el seguiment presenta una biòpsia de CIN3.
L’edat mitjana de les 105 pacients incloses era de 30,5 anys (rang 18-56), 54,3% eren fumadores i un 74,3% nul·lípares. En global es pot parlar d’una taxa de curació del 44%, una taxa de regressió parcial del 21,5%, una taxa de persistència del 11,8% i una taxa de progressió del 22,6% posterior a 2 anys de seguiment. Sabent que la infecció del CMV s’associa a canvis en la distribució d’expressió dels receptors de les cèl·lules NK, s’ha demostrat que aquest canvi, concretament l’expressió del receptor activador NKG2C podria ajudar a predir l’evolució de les lesions de les pacients amb CIN2. En l’anàlisis dels cofactors, la clamídia [OR: 19,1 (95% IC: 1,9-189,7)], el VPH16 [OR: 5,9 (95% IC: 1,7-14,6)], i la citologia prèvia de HSIL [OR: 4,8 (95% IC: 1,7-13,7)], han demostrat ser factors predictors de CIN2+ en el model multivariant [ASC (area sota la corba): 0,829 (95% IC: 0,744-0,913)]. Per tant les altes taxes de regressió del CIN2 suporten el maneig conservador en pacients seleccionades. L’estudi de marcadors predictors de l’evolució del CIN2 pot ajudar a individualitzar millor el maneig i evitar contizacions innecessaries.Cervical Intraepithelial Neoplasia (CIN) is a precursor lesion of cervical cancer with a well-known natural history that starts from an infection caused by the human papillomavirus (HPV). There are multiple cofactors that can modulate the capacity of spontaneous CIN regression or progression. Unfortunately, there are no predictive factors regarding the evolution of CIN2 that could be used clinically to individualize the appropriate treatment and follow-up. The CIN2 is an intermediate state between CIN1 and CIN3 with spotaneous regression rates of 40-60% and progression rate of 10-20% described in the literature. Althought conization is the usual management of CIN2 lesions, current American (ASCCP) and Spanish (SEGO) guidelines propose conservative management in young and selected patients to avoid their over-treatment. NK cells (natural killer cells), involved in the innate immune response, could be related with this capacity of CIN2 to regress spontaneously. In order to identify markers that can predict the CIN2 evolution, aims to study the immune system, specifically Natural Killer cells. NK cells found in peripheral blood have the ability to remove infected or tumor cells wich have lost the expression of major histocompatibility complex class I (MHC I) in pathological conditions, that would prevent the activation of T cells’ immune response. Our hypothesis is that a deterioration of the NK functionality, analysed through a lower percentatge of NK cells receptors expression, could consequently decrease the capacity of CIN2 spontaneously regression. Between December 2011 and October 2013, patients with histological diagnosis of CIN-2 cervical biopsy, older than 18 years old, who agreed to follow up every 4 months for at least 2 years, were prospectively recruited. Unsatisfactory colposcopy and immunosuppressive treatment were considered exclusion criteria. NK cells, serologies (HIV, Herpes 2, HBV, HCV, Chlamydia trachomatis and Lues), previous abnormal cytology, genotyping of high-risk HPV and epidemiological features were reported at baseline in all women included. Total regression was defined as two consecutive negative cytologies and no evidence of colposcopic lesions, partial regression if final biopsy showed CIN1, persistence when biopsy showed CIN2, and progression if a CIN3 biopsy was detected at any time during follow-up. The mean age of 105 patients included was 30.5 years (range, 18-56), 54.3% were smokers and 74.3% were nulliparous. Overall, the rate of spontaneous total regression at 2 years of follow-up was 44%, 21.5% presented partiral regression, 11.8% had persistent disease, while 7.8% progressed. Knowing that CMV infection is associated with redistribution of NK cells receptors, particularly NKG2C expression, this study showed that this change could help predict the evolution of CIN2 lesions. As well as, chlamydia immunity [OR: 19.1 (95% CI 1.9 to 189.7)], VPH16 infection [OR 5.9 (95% CI 1.7 to 14.6)] and previous HSIL cytology [OR 4.8 (95% CI 1.7 to 13.7)], were statistically associated with non-regression (CIN2+) in the multivariate model [ASC (area under the curve): 0.829 (95% CI 0.744 to 0.913)]. The high regression rate of CIN2 supports clinical observation in selected patients. Study of biomarkers predicting CIN2 evolution would have a great clinical value and could reduce unnecessary cone excision.
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Coelho, Raquel Autran [UNIFESP]. "Expressão de topoisomerase II alfa e de caspase-3 ativada em lesão intra-epitelial cervical escamosa de baixo grau." Universidade Federal de São Paulo (UNIFESP), 2008. http://repositorio.unifesp.br/handle/11600/9620.
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Objetivos: Estudar a expressao imuno-histoquimica de topoisomerase IIƒ¿ e de caspase-3 ativada, marcadores de proliferacao e de apoptose, respectivamente, a deteccao de DNA HPV e a evolucao da lesao cervical em mulheres portadoras de lesao intra-epitelial escamosa de baixo grau (LBG). Metodos: Foram avaliadas 40 mulheres portadoras de LBG e 32 sem neoplasia cervical, diagnosticadas por exame cito-colpo-histopatologico, quanto a imunoexpressao de topoisomerase IIƒ¿ e de caspase-3 ativada e quanto a deteccao de DNA HPV por PCR consensual (GP5+/GP6+) em material de esfregaco cervico-vaginal. Os achados foram relacionados as variaveis clinicas das pacientes e a evolucao clinica das lesoes cervicais em 12 meses. As pacientes assinaram termo de consentimento livre e esclarecido. Resultados: A media percentual de celulas imunomarcadas por topoisomerase foi de 11,71% e 4,13%, no grupo com LBG e controle, respectivamente, com diferenca estatisticamente significante. Observou-se que houve expressao de caspase-3 em 17 (42,5%) e em 5 (15,63%) pacientes com e sem LBG, respectivamente, com diferenca estatisticamente significante. Foi detectado HPV DNA em 65% das pacientes com LBG e em 59,4% das pacientes sem lesao cervical, sem relacao com a expressao de topoisomerase IIƒ¿ ou caspase-3. Na presenca de DNA-HPV, a expressao de topoisomerase IIƒ¿ no grupo com LBG foi significativamente maior do que em fragmentos sem lesao. Nao foi observada diferenca quanto a evolucao da lesao cervical em 12 meses de acordo com a imunoexpressao de topoisomerase IIƒ¿. Com relacao a caspase-3 ativada, a maioria das pacientes com imuno-histoquimica negativa teve regressao da lesao cervical. Conclusoes: A imunoexpressao de topoisomerase IIƒ¿ e de caspase-3 ativada podem ser considerados marcadores de proliferacao e de apoptose em lesao cervical de baixo grau, sem relacao com a presenca de DNA-HPV.
Purpose: To evaluate the correlation between the expression of topoisomerase II alpha, active caspase-3 and infection with human papillomavirus in low-grade cervical intraepithelial lesion and in the normal cervix, and whether they might influence susceptibility to, or evolution of, cervical lesion. Patients and methods: Forty cervical biopsies patients with low-grade cervical intraepithelial lesion and thirty-two with normal cervix were stained by immunohistochemistry for topoisomerase IIá and active caspase-3 and were investigated for the presence of HPV on exfoliated cells by general primer GP5+/6+ PCR amplification of DNA. These findings were correlated with clinicopathological features of the patients including their clinical outcome after twelve months. Subjects provided written informed consent. Results: Low-grade CIN patients as a group had a significantly higher expression of topoisomerase II alpha compared to controls, without correlation to disease outcome at 12 months. Caspase-3 was expressed in 42.5% of CIN patients and in 15.63% without disease, and most of women without caspase-3 receded cervical lesion. HPV DNA testing was positive in 65% of the patients with cervical lesion, and in 59.4% of the control group and was not associated to the expression of topoisomerase IIá or active caspase-3. In the presence of a positive HPV DNA testing, women with cervical lesion had a significantly higher expression of topoisomerase II alpha compared to controls. Conclusion: Topoisomerase II alpha and active caspase-3 might be useful diagnostic and prognostic markers in low-grade cervical lesions, delaying a better follow-up.
CNPq: 134106/2005-9
TEDE
BV UNIFESP: Teses e dissertações
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Pias, Andressa de Azambuja. "Proex C para o diagnóstico de lesões intra-epiteliais no colo do útero." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2012. http://hdl.handle.net/10183/39655.
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Foi realizada uma análise quantitativa sistemática da literatura para verificar a acurácia do biomarcador ProEx C em pacientes com ASC-US, ASCH e SIL. Metodologia: A pesquisa foi realizada no MEDLINE (PubMed e OVID), EMBASE, LILACS, IBECS, BIOSIS, Web of Science, SCOPUS, desde 1966 até Novembro de 2011. Esta revisão esteve centrada em estudos que cumpriram as três condições para a seleção do estudo, que incluem teste de Papanicolaou, teste de triagem ProEx C e histopatologia como o teste de referência. Resultados: Cinco estudos, incluindo 713 mulheres, foram analisados. Das biopsias positivas, 83% (355/429) foram positivas para ProEx C, enquanto 14% (41/284) das biópsias negativas foram positivas para ProEx C. A sensibilidade combinada foi de 83% (95% IC, 79-87) e especificidade foi de 85% (95% IC, 80-89) usando o soaftware Meta-Disc. Para lesão cervical vs biópsia positiva ou negativa, a área sob a curva (AUC) foi de 0,90 com valor do ponto Q * de 0,84. Conclusão: nossos dados concordam com a hipótese de que ProEx C representa um evento precoce na carcinogênese cervical e que poderiam estar associados com a iniciação e progressão de lesões cervicais e, se expressados nos exames estudados podem revelar maior acurácia diagnóstica destes exames.Undertook a quantitative systematic review of the literature to ascertain the accuracy of the biomarker ProEx C in patients with ASC-US, ASC-H and SIL. Methods: A comprehensive search of the MEDLINE (PubMed and OVID interface), EMBASE, LILACS, IBECS, BIOSIS, Web of Science, SCOPUS, index from 1966 to November 2011. This review focused on studies that fulfill the three mandatory conditions for study selection that include Pap Test, triage testing ProEx C and histopathology like the reference test. Results: Five studies, including 713 women, were analyzed. 83% (355/429) of positive biopsy were positive for ProEx C activity, while 14% (41/284) of the negative biopsy were positive for ProEx C activity. Pooled sensitivity was 83% (95% IC, 79 to 87) and specificity was 85% (95% IC, 80-89) using software Meta-Disc. For cervical lesion vs positive or negative biopsy, the area under the curve (AUC) was 0.90 with Q* point value of 0.84. Conclusion: our data agree with the hypothesis that ProEx C represents an early event in cervical carcinogenesis that could be associated with the initiation and progression of cervical lesions and is expressed in the studied tests may reveal greater diagnostic accuracy of these tests.