Journal articles on the topic 'Papillomaviruses Diagnosis'
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Korsak, K. S., and E. V. Voropaev. "Phylogenetic features of papillomaviruses and their significance in the diagnosis of papillomavirus infection." Health and Ecology Issues, no. 4 (December 28, 2020): 23–28. http://dx.doi.org/10.51523/2708-6011.2020-17-4-3.
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Viruses belonging to the Papillomaviridae family have been isolated from mammals, birds and reptiles. The analysis of the genome structure of more than 240 different types of papillomaviruses has made it possible to better understand their evolutionary path. The existing data indicate that many diverse evolutionary mechanisms have influenced their phylogenetic tree. For more than 400 million years, papillomaviruses have occupied various ecological niches. Niche sorting was followed by extensive periods of host-parasite co-evolution. Adaptation to different host tissues, as well as to changing environmental conditions can explain some features of the members of the Papillomaviridae family, one of which is human papillomavirus (HPV), having an important clinical significance. The study of the driving mechanisms of the evolution will help to change the notions about HPV virulence, character of its spread, epidemiology, as well as the pathogenesis and the course of oncologic diseases caused by it. This review highlights some moments of the evolutionary history of papillomaviruses which created a background for the development of oncogenic features of certain HPV types.
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Unger, Elizabeth R. "In Situ Diagnosis of Human Papillomaviruses." Clinics in Laboratory Medicine 20, no. 2 (June 2000): 289–301. http://dx.doi.org/10.1016/s0272-2712(18)30063-5.
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Sanz, Alexandra, Erica Miller, Nikki Harley, and Laura Coffee. "Papillomatosis in a raccoon (<em>Procyon lotor</em>)." Wildlife Rehabilitation Bulletin 40, no. 1 (October 7, 2022): 22–26. http://dx.doi.org/10.53607/wrb.v40.255.
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Papillomaviruses are species-specific double-stranded DNA viruses with at least 50 species of mammals. Although well-studied in humans, papillomaviruses in the raccoon (Procyon lotor) are not well characterized, and few cases have been published. Therefore, when the disease is encountered in a rehabilitation center, definitive diagnosis and treatment in the raccoon can be unclear. This case study outlines the characteristic gross and histologic lesions of an affected individual to facilitate identification and treatment of this disease in the future. In the case of this juvenile raccoon, ulcerated exophytic lesions on the bridge of its nose and right forelimb digit were seen grossly, with the presence of koilocytes and hyperkeratosis observed histologically. These findings are consistent with other documented cases of papillomavirus in raccoons and canines. Affected raccoons do not require extensive treatment, as raccoon papillomatosis is considered self-limiting.
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Greenblatt, Rebecca J. "Human papillomaviruses: Diseases, diagnosis, and a possible vaccine." Clinical Microbiology Newsletter 27, no. 18 (September 2005): 139–45. http://dx.doi.org/10.1016/j.clinmicnews.2005.09.001.
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Frías, Isaac A. M., Karen Y. P. S. Avelino, Rafael R. Silva, César A. S. Andrade, and Maria D. L. Oliveira. "Trends in Biosensors for HPV: Identification and Diagnosis." Journal of Sensors 2015 (2015): 1–16. http://dx.doi.org/10.1155/2015/913640.
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The conventional methodologies used for the detection of human papillomavirus (HPV) present actually robust and reproducible advantages. However, at the same time, they involve complex protocols that sometimes are difficult to popularize. Over the first half of XX century, the adequate treatment of complex and delicate processes from a simple instrumental base seemed a fundamental and intrinsic contradiction. However, interdisciplinary trends have allowed the manipulation of tissues, proteins, and nucleic acids through innovative increasingly smaller devices. The proper diagnosis of HPV has seen great advances since biosensor researchers are employing its virus strains as models to study the interactions between the biorecognition element and the transducer. Additionally, all recent improvements and trends that material sciences, biotechnology, and data processing scientists excel for biosensors can be applied for the HPV detection platforms. In this review, we highlight the recent trends on materials, nanomaterials, and transducers for the specific detection and differentiation of HPV strains. The most influential methods for the detection and identification of these papillomaviruses include optical, electrochemical, and piezoelectric transducers; we will visit their sensibility and advantages. Additionally, we highlight the factors that contributed to the increasing importance of these biodevices as potential substitutes to conventional diagnostic methods.
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Alexander, Kenneth A., and William C. Phelps. "Recent advances in diagnosis and therapy of human papillomaviruses." Expert Opinion on Investigational Drugs 9, no. 8 (August 2000): 1753–65. http://dx.doi.org/10.1517/13543784.9.8.1753.
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Silverberg, Steven G. "Molecular Diagnosis and Prognosis in Gynecologic Oncology." Archives of Pathology & Laboratory Medicine 123, no. 11 (November 1, 1999): 1035–40. http://dx.doi.org/10.5858/1999-123-1035-mdapig.
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Abstract Currently, molecular pathology plays a limited role in improving patient outcome in gynecologic oncology. However, molecular investigation is providing important insights into the epidemiology, pathogenesis, and progression of female genital cancers. Future roles should include prediction of poor outcome in low-risk cases, more accurate staging of multifocal tumors, identification of new precursor lesions, and prediction of response to specific therapeutic regimens. Gene therapy of some malignant tumors may become important in the near future. In the immediate future, however, the most significant role of molecular pathology may be in the screening and triage of putative cervical cancer precursors and in the possible prophylaxis of these lesions by means of a vaccine or vaccines against human papillomaviruses.
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Dunjic, Momir, Slavisa Stanisic, Dejan Krstic, Miodrag Stanisic, Z. Jovanovic Ignjatic, and Marija Dunjic. "Integrative Approach to Diagnosis of Genital Human Papillomaviruses (HPV) Infection of Female." Acupuncture & Electro-Therapeutics Research 39, no. 3 (October 10, 2014): 229–39. http://dx.doi.org/10.3727/036012914x14109544776051.
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Coutlee, François, Danielle Rouleau, Alex Ferenczy, and Eduardo Franco. "The Laboratory Diagnosis of Genital Human Papillomavirus Infections." Canadian Journal of Infectious Diseases and Medical Microbiology 16, no. 2 (2005): 83–91. http://dx.doi.org/10.1155/2005/798710.
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Human papillomaviruses (HPVs) are the etiological agents of several genital cancers, including cancer of the uterine cervix. The detection of HPV infection in genital samples may increase the sensitivity of primary and secondary screenings of cervical cancer. HPV testing may also improve the specificity of screening programs, resulting in the avoidance of overtreatment and cost savings for confirmatory procedures. The major determinants of clinical progression of HPV infection include persistence of HPV infection, involvement of high-risk HPV types, high HPV viral load, integration of viral DNA and presence of several potential cofactors. Signal amplification HPV-DNA detection techniques (Hybrid Capture II, Digene Corporation, USA) are standardized, commercially available, and capable of detecting several high-risk HPV types. They also increase the sensitivity of screening for high-grade lesions in combination with cytology. The sensitivity of these techniques to detect high-grade lesions is higher than that of cytology, but the referral rate for colposcopy is greater. These techniques are approved for the triage to colposcopy of women with cervical smears interpreted as atypical squamous cells of undetermined significance. Triage and screening for cervical cancer using HPV will probably be restricted to women aged 30 years or older because of the high prevalence of infection in younger women. Amplification techniques are ideal for epidemiological studies because they minimize the misclassification of HPV infection status. These techniques can detect low HPV burden infections. Consensus primers amplify most genital types in one reaction, and the reverse hybridization of amplicons with type-specific probes allows for the typing of HPV-positive samples. Consensus PCR assays are currently under evaluation for diagnostic purposes. HPV testing is currently implemented for the clinical management of women.
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Spinillo, Arsenio A., Mattia M. Dominoni, Anna A. C. Boschi, Cecilia C. Sosso, Giacomo G. Fiandrino, Stefania S. Cesari, and Barbara B. Gardella. "Clinical Significance of the Interaction between Human Papillomavirus (HPV) Type 16 and Other High-Risk Human Papillomaviruses in Women with Cervical Intraepithelial Neoplasia (CIN) and Invasive Cervical Cancer." Journal of Oncology 2020 (October 26, 2020): 1–9. http://dx.doi.org/10.1155/2020/6508180.
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The aim is to evaluate the clinical consequences of coinfection between HPV 16 and other high-risk HPVs among women with a histological diagnosis of CIN or invasive cervical cancer. A total of 2985 women, with a diagnosis of either CIN or cancer (<IB) on cervical or cone biopsy, were included. HPV genotypes were identified using the INNO-LiPA HPV genotyping assay, version EXTRA, on cervical scraping, before the colposcopic evaluation and the colposcopic biopsies or conization. In the overall population, HPV16 interacted positively with HPV18 (RR = 2, 95% CI 1.5–2.6) and negatively with HPV33, 51, 52, and 66, in log-linear analysis. There was an excess of CIN3 diagnoses among subjects coinfected with HPV16 and HPV18 or HPV52, although the absolute number of cases was relatively small. In a logistic model, the odds ratio of CIN3+ associated with coinfection of HPV16 and HPV18 (OR = 3.8, 95% CI 2.5–5.7, p = 0.004 compared to single HPV16) or HPV52 (OR = 3.6, 95% CI 2.6–5.1, p = 0.009 compared to single HPV) was higher than that associated with single HPV 16 infections. Finally, multiple infections had no effect on residual disease and did not influence the recurrence of high-grade CIN during a median follow-up of 25 months (IR 17–41). HPV16 interacted positively with HPV18 and negatively with HPV33, 51, 52, and 66 supporting the notion that HPV16 interacts mostly negatively with other HR-HPVs in CIN lesions. Among specimens coinfected with HPV16 and 18 or 52, there was an excess of CIN3+ although the impact on the prevalence of severe cervical lesions was limited.
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Badal, Vinay, Linda S. H. Chuang, Eileen Hwee-Hong Tan, Sushma Badal, Luisa L. Villa, Cosette M. Wheeler, Benjamin F. L. Li, and Hans-Ulrich Bernard. "CpG Methylation of Human Papillomavirus Type 16 DNA in Cervical Cancer Cell Lines and in Clinical Specimens: Genomic Hypomethylation Correlates with Carcinogenic Progression." Journal of Virology 77, no. 11 (June 1, 2003): 6227–34. http://dx.doi.org/10.1128/jvi.77.11.6227-6234.2003.
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ABSTRACT Infection with genital human papillomaviruses (HPVs) is the primary cause of cervical cancer. The infection is widespread, and little is known about the secondary factors associated with progression from subclinical infection to invasive carcinoma. Here we report that HPV genomes are efficiently targeted in vivo by CpG methylation, a well-known mechanism of transcriptional repression. Indeed, it has been shown previously that in vitro-methylated HPV type 16 (HPV-16) DNA is transcriptionally repressed after transfection into cell cultures. By using a scan with the restriction enzyme McrBC, we observed a conserved profile of CpG hyper- and hypomethylation throughout the HPV-16 genomes of the tumor-derived cell lines SiHa and CaSki. Methylation is particularly high in genomic segments overlying the late genes, while the long control region (LCR) and the oncogenes are unmethylated in the single HPV-16 copy in SiHa cells. In 81 patients from two different cohorts, the LCR and the E6 gene of HPV-16 DNA were found to be hypermethylated in 52% of asymptomatic smears, 21.7% of precursor lesions, and 6.1% of invasive carcinomas. This suggests that neoplastic transformation may be suppressed by CpG methylation, while demethylation occurs as the cause of or concomitant with neoplastic progression. These prevalences of hyper- and hypomethylation also indicate that CpG methylation plays an important role in the papillomavirus life cycle, which takes place in asymptomatic infections and precursor lesions but not in carcinomas. Bisulfite modification revealed that in most of the HPV-16 genomes of CaSki cells and of asymptomatic patients, all 11 CpG dinucleotides that overlap with the enhancer and the promoter were methylated, while in SiHa cells and cervical lesions, the same 11 or a subset of CpGs remained unmethylated. Our report introduces papillomaviruses as models to study the mechanism of CpG methylation, opens research on the importance of this mechanism during the viral life cycle, and provides a marker relevant for the etiology and diagnosis of cervical cancer.
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Gupta, Shilpi, Prabhat Kumar, Jayant Maini, and Harsimrut Kaur. "Epigenetic Biomarkers in Head and Neck Cancer." Journal of Cancer Genetics and Biomarkers 1, no. 2 (November 23, 2018): 41–50. http://dx.doi.org/10.14302/issn.2572-3030.jcgb-18-2428.
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Head and neck cancers (HNCs) are the most prevalent and aggressive type of cancers. Genetic, epigenetic, environmental and viral risk-factors are associated with HNC carcinogenesis. Persistent infection of oncogenic human papillomaviruses (HR-HPVs) represent distinct biological, molecular and epigenetic entities in HNCs. There are three main epigenetic mechanisms that regulate transcription, these are DNA methylation, histone modifications and alteration in non-coding RNA networks, which can dissected to identify innovative and accurate epigenetic biomarkers for diagnosis and prognosis of HNC patients. Due to the lacunae of accurate distinctive biomarkers for the definite diagnosis of HNC, the identification of predictive epigenetic markers is necessary that might modify or increase HNC patient’s survival. In this mini review, we briefly summarize the current knowledge of different epigenetic biomarkers in HNC.
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Pisarska, Justyna, and Katarzyna Baldy-Chudzik. "MicroRNA-Based Fingerprinting of Cervical Lesions and Cancer." Journal of Clinical Medicine 9, no. 11 (November 15, 2020): 3668. http://dx.doi.org/10.3390/jcm9113668.
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The regulatory functions of microRNA (miRNA) are involved in all processes contributing to carcinogenesis and response to viral infections. Cervical cancer in most cases is caused by the persistence of high-risk human papillomavirus (HR-HPV) infection. While oncogenic human papillomaviruses induce aberrant expression of many cellular miRNAs, this dysregulation could be harnessed as a marker in early diagnosis of HR-HPV infection, cervical squamous intraepithelial lesions, and cancer. In recent years, growing data indicate that miRNAs show specific patterns at various stages of cervical pathology. The aim of this review is to systematize current reports on miRNA capacity that can be utilized in personalized diagnostics of cervical precancerous and cancerous lesions. The analysis of the resources available in online databases (National Center for Biotechnology Information—NCBI, PubMed, ScienceDirect, Scopus) was performed. To date, no standardized diagnostic algorithm using the miRNA pattern in cervical pathology has been defined. However, the high sensitivity and specificity of the reported assays gives hope for the development of non-invasive diagnostic tests that take into account the heterogeneity of tumor-related changes. Due to this variability resulting in difficult to predict clinical outcomes, precise molecular tools are needed to improve the diagnostic and therapeutic process.
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Bahramabadi, R., M. K. Arababadi, M. Iranpour, E. Mohebbi, Z. Honarvar, M. F. S. Abadi, S. A. Rostami, et al. "Evaluation of Cervical Cancer Screening Tools; INNO-LiPA® HPV Genotyping Extra-II Assay versus E7/E6 oncoproteins, How is reliable and practical?" Pakistan Journal of Medical and Health Sciences 15, no. 5 (May 30, 2021): 1276–81. http://dx.doi.org/10.53350/pjmhs211551276.
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Background: High-Risk Human papillomavirus (HR-HPV) has been well established as the cervical cancer (CC) risk factor. In recent years, various diagnostic methods of human papillomaviruses (HPV) have been developed to promote sensitivity and specificity of CC screening which leads to a low mortality rate. This study aimed to compare diagnostic test metrics of two HPV diagnostic techniques, including Western blot and INNO-LiPA HPV Genotyping Extra II assay methods in asymptomatic or subclinical patients, among the South-Eastern Iranian women. Methods: 323 women were referred to the Pathology and Stem Cell Research Center, from February 2018 to January 2020. HPV-DNA with the INNO-LiPA HPV Genotyping Extra-II Assay kit and the western blot assays for HPV E7 and E6 assessment were employed. Results: Overall, 163 (50.4%) samples were dysplastic pap smear, the specificity of the HPV DNA test by INNO-LiPA HPV Genotyping Extra-II Assay test was significantly higher than the E7/E6 oncoproteins finding (67.3 vs. 49.9%), and the sensitivity was lower (96.6 vs. 74.8%), respectively. Conclusions: HR-HPV E7/E6 oncoproteins expression was evaluated as a possible novel biomarker for CC screening in pap smear as the preliminary test with satisfactory diagnostic values for HR-HPV types 16 and 18. The corresponding diagnostic values may be further improved by combining HPV DNA tests with the INNO-LiPA HPV Genotyping Extra-II test. Also, they may prove helpful for HR-HPV infection diagnosis in cases that the patients are asymptomatic or subclinical. Keywords: Cervical Cancer; Human Papillomavirus (HPV); Diagnostic Screening Programs; Oncogene Proteins
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Xu, Xinnan, Rui Kong, Xiaoqing Liu, Pingan He, and Qi Dai. "Prediction of High-Risk Types of Human Papillomaviruses Using Reduced Amino Acid Modes." Computational and Mathematical Methods in Medicine 2020 (June 18, 2020): 1–10. http://dx.doi.org/10.1155/2020/5325304.
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A human papillomavirus type plays an important role in the early diagnosis of cervical cancer. Most of the prediction methods use protein sequence and structure information, but the reduced amino acid modes have not been used until now. In this paper, we introduced the modes of reduced amino acids to predict high-risk HPV. We first reduced 20 amino acids into several nonoverlapping groups and calculated their structure and physicochemical modes for high-risk HPV prediction, which was tested and compared with the existing methods on 68 samples of known HPV types. The experiment result indicates that the proposed method achieved better performance with an accuracy of 96.49%, indicating that the reduced amino acid modes might be used to improve the prediction of high-risk HPV types.
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Molina-Ruiz, Ana M., Carlos Santonja, Arno Rütten, Lorenzo Cerroni, Heinz Kutzner, and Luis Requena. "Immunohistochemistry in the Diagnosis of Cutaneous Viral Infections—Part I. Cutaneous Viral Infections by Herpesviruses and Papillomaviruses." American Journal of Dermatopathology 37, no. 1 (January 2015): 1–14. http://dx.doi.org/10.1097/dad.0000000000000203.
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Chernesky, Max A., and David Patrick. "Canadian Laboratory Standards for Sexually Transmitted Infections: Best Practice Guidelines." Canadian Journal of Infectious Diseases and Medical Microbiology 16, no. 1 (2005): 11. http://dx.doi.org/10.1155/2005/717045.
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Sexually transmitted infections (STI) continue to spread, and show no international boundaries. Diseases such as gonorrhea and syphilis, which we thought were under control in Canadian populations, have increased in incidence. Sexually transmitted or associated syndromes such as cervicitis, enteric infections, epididymitis, genital ulcers, sexually related hepatitis, ophthalmia neonatorum, pelvic inflammatory disease, prostatitis and vulvovaginitis present a challenge for the physician to identify the microbial cause, treat the patient and manage contacts. During the past 10 years, new technologies developed for the diagnosis of STIs have provided a clearer understanding of the real accuracy of traditional tests for the diagnosis of infections caused byChlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, herpes simplex viruses, hepatitis B virus, human papillomaviruses, HIV,Haemophilus ducreyi, Trichomonas vaginalisand mycoplasmas. This has presented a major challenge to the diagnostic laboratory, namely, selecting the most sensitive and specific test matched with the most appropriate specimens to provide meaningful and timely results to facilitate optimal patient care.
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Noël, Jean-Christophe, and Philippe Simon. "Limitations on the Detection Rate of High-Risk HPV by Hybrid Capture 2 Methodology in High Grade Intraepithelial (HSIL) or Atypical Squamous Cells-Cannot Exclude HSIL (ASC-H) Cytological Lesions with Proved CIN2+." Analytical Cellular Pathology 2015 (2015): 1–4. http://dx.doi.org/10.1155/2015/746502.
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Recent literature data suggest that the high-risk human papillomaviruses (HR-HPVs) testing with several molecular techniques could be an alternative to cytology in the detection of cervical intraepithelial neoplasias of grade 2 or worse (CIN2+). However, any molecular techniques have its own limits and may give false negative results which must be clearly known before undertaking a primary HPV screening. This study aims to evaluate the performance of the high-risk HPV hybrid capture II detection kit (HCII) which is considered as a “gold standard technique” in a series of 100 women having proved both cytological lesions of atypical squamous cells-cannot exclude an HSIL (ASC-H) or high-grade squamous intraepithelial lesion (HSIL) and histological lesions of CIN2+. The clinical sensitivity of HCII in women with a cytological diagnosis of ASC-H/HSIL and a diagnosis of CIN2+ is high but not absolute and estimated at 96% (95,6% and 100% of women with a diagnosis of CIN2/3 or invasive squamous cell carcinoma, resp.). These data although they are infrequent must be clearly referred before to start an HPV primary screening of CIN2+ especially with HCII methodology.
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Steele, C., and E. J. Shillitoe. "Viruses and Oral Cancer." Critical Reviews in Oral Biology & Medicine 2, no. 2 (April 1991): 153–75. http://dx.doi.org/10.1177/10454411910020020201.
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Oral cancer is a disease with a complex etiology. There is evidence for important roles of smoking, drinking, and genetic susceptibility, as well as strong indications that DNA viruses could be involved. The herpes simplex virus type I has been associated with oral cancer by serological studies, and animal models and in vitro systems have demonstrated that it is capable of inducing oral cancer. Papillomaviruses are found in many oral cancers and are also capable of transforming cells to a malignant phenotype. However, both virus groups depend on co-factors for their carcinogenic effects. Future research on viruses and oral cancer is expected to clarify the role of these viruses, and this will lead to improvements in diagnosis and treatment of the disease.
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Wang, Cong, Yabing Hai, Xiaoqing Liu, Nanfang Liu, Yuhua Yao, Pingan He, and Qi Dai. "Prediction of High-Risk Types of Human Papillomaviruses Using Statistical Model of Protein “Sequence Space”." Computational and Mathematical Methods in Medicine 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/756345.
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Discrimination of high-risk types of human papillomaviruses plays an important role in the diagnosis and remedy of cervical cancer. Recently, several computational methods have been proposed based on protein sequence-based and structure-based information, but the information of their related proteins has not been used until now. In this paper, we proposed using protein “sequence space” to explore this information and used it to predict high-risk types of HPVs. The proposed method was tested on 68 samples with known HPV types and 4 samples without HPV types and further compared with the available approaches. The results show that the proposed method achieved the best performance among all the evaluated methods with accuracy 95.59% andF1-score 90.91%, which indicates that protein “sequence space” could potentially be used to improve prediction of high-risk types of HPVs.
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Volchenko, A. N. "DYNAMICS OF CERVICAL CANCER INCIDENCE RATE AND LEVELS OF AWARENESS ABOUT ITS PREVENTION AMONG DIFFERENT POPULATION GROUPS." Health and Ecology Issues, no. 2 (June 28, 2014): 25–30. http://dx.doi.org/10.51523/2708-6011.2014-11-2-5.
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Purpose. Determine the features of long-term dynamics of invasive and preinvasive cervical cancer (CC) in Gomel region over 1990-2010 and to determine the level of awareness about CC prevention in different population groups. Material and methods. Retrospective epidemiological analysis, method of questioning and statistical information processing were applied. The results. It was found out that there is positive tendency of manifestations of the CC epidemic process in Gomel region in comparison with the national indices whereas the long-term levels of the CC incidence and mortality rates in Gomel region were higher that average ones. The study revealed a low level of knowledge about CC and its prevention among different population groups. Conclusions. It was calculated that the introduction of the diagnosis of human papillomaviruses (HPV) by PCR in Gomel region since 2002 led to twice intense preinvasive CC detection and more frequent diagnosis of invasive CC stage I than in Belarus in general. The study shows the limiting role of the low awareness of CC in the implementation of preventive measures.
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Rodu, B. "New Approaches to the Diagnosis of Oral Soft-Tissue Disease of Viral Origin." Advances in Dental Research 7, no. 2 (August 1993): 207–12. http://dx.doi.org/10.1177/08959374930070021301.
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Molecular biology is changing the face of diagnostic medicine, and infectious diseases of the oral soft tissues are among the targets of these advances in biotechnology. As an illustration of these concepts, a PCR-based detection and typing system for human papillomaviruses (HPVs) will be discussed. A single "consensus" set of oligomeric nucleotide primers can be used to amplify a 571- to 594-base-pair region of the E1 open reading frame of HPV 6, 11, 16, and 18. These HPV types are commonly associated with preneoplastic and cancerous lesions of the genital, respiratory, and digestive tracts. PCR amplification yields single bands of similar size for these viruses by agarose gel electrophoresis. Digestion of the resultant products by the restriction endonuclease AccI yields distinctive and reproducible banding patterns by polyacrylamide gel electrophoresis (with ethidium bromide) due to their internal sequence diversity. The system is sensitive; without radioisotopes, it can detect and type HPV 18 in as little as 100 pg of DNA from HeLa cells. We have used it to confirm HPV in fresh-frozen tumors. Computer sequence analysis can be used to modify the system for the detection of new HPV types as they are characterized. Other applications of molecular-biology-based detection systems for infectious diseases of the head and neck region will be discussed.
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Chen, Zigui, Mark Schiffman, Rolando Herrero, and Robert D. Burk. "Identification and characterization of two novel human papillomaviruses (HPVs) by overlapping PCR: HPV102 and HPV106." Journal of General Virology 88, no. 11 (November 1, 2007): 2952–55. http://dx.doi.org/10.1099/vir.0.83178-0.
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Complete genomes of HPV102 (8078 bp) and HPV106 (8035 bp) were PCR amplified and cloned from cervicovaginal cells of a 49-year-old Hispanic female with reactive changes on her Pap test and a 42-year-old Hispanic female with a Pap test diagnosis of atypical squamous cells of unknown significance (ASCUS), respectively. The nucleotide sequence similarity of the complete L1 open reading frame (ORF) determined that HPV102 and HPV106 are most closely related to HPV83 (84.1 % identity) and HPV90 (83.5 % identity), respectively, placing them in the genital HPV groups, papillomaviruses species α3 and α15. HPV102 and HPV106 contain five early genes (E6, E7, E1, E2, and E4) and two late genes (L2 and L1), and both lack an E5 ORF. On the basis of phylogenetic analyses and available clinical information, these two novel HPV types expand the heterogeneity of HPVs detected in the lower genital tract.
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Zorzato, Pierpaolo, Mattia Zambon, Silvia Gori, Helena Frayle, Maria Teresa Gervasi, and Annarosa Del Mistro. "Leptomeningeal Carcinomatosis of a Poorly Differentiated Cervical Carcinoma Caused by Human Papillomavirus Type 18." Viruses 13, no. 2 (February 16, 2021): 307. http://dx.doi.org/10.3390/v13020307.
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Cervical cancer is caused by a persistent infection with high-risk types of Papillomaviruses (hrHPV); HPV16 and HPV18 are associated with about 70% of the cases. In the last decades the introduction of a cervical cancer screening has allowed a decrease in cervical cancer incidence and mortality; regular adhesion to the screening procedures, by pap test or HPV test, and colposcopy, according to the international guidelines, prevents cancer development and allows for diagnosis at the early stages. Nowadays, in industrialized countries, it is not common to diagnose this pathology in advanced stages, and this occurrence is frequently associated with patient’s unattendance of cervical screening programs. We describe a case of delayed diagnosis of cervical cancer, posed only after the onset of the neurological symptoms caused by leptomeningeal metastases, despite a two-year history of abnormal cytology. The endocervical mass was analyzed by immunohistochemistry, and search and typing of HPV sequences was performed by PCR in the meningeal carcinomatous cells. A poorly differentiated squamous cell carcinoma was diagnosed, and HPV18 sequences were detected. This rapidly fatal case highlights the importance of following the evidence-based recommended protocols and the preventive role of the population-based cervical cancer screening programs.
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Nakazaki, Natsuko, Masayoshi Zaitsu, Koji Mikami, Shunsuke Yui, Ayumi Kanatani, Takushi Nakatani, Akiko Ito, et al. "Coincidence of HPV11-Positive Urethral Condyloma Acuminatum and HPV-Negative Multiple Bladder Papillomas in a Female." Case Reports in Medicine 2012 (2012): 1–3. http://dx.doi.org/10.1155/2012/602819.
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Human papillomaviruses (HPVs) are associated with proliferative lesions in a variety of human epithelial types. A 38-year-old female presented with a diagnosis of urethral condyloma acuminatum. She underwent transurethral resection of the urethral condyloma. At that time, multiple (five) bladder tumors were simultaneously found and also removed by transurethral resection. Four of the bladder tumors were diagnosed as squamous papilloma, and the other was urothelial inverted papilloma. Postoperative course was uneventful. Genomic DNA was extracted from 10 μm thick sections of each bladder tumor as well as urethral condyloma. Then, 16 types of HPV DNA sequences were assessed with the PapiPlex method using genomic DNA samples extracted from each bladder tumor as well as urethral condyloma. HPV-11 was detected in DNA extracted from the urethral condyloma, while no HPV DNA sequences were positive in any of the genomic DNA samples extracted from the bladder tumors.
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Viladiu, P., F. X. Bosch, X. Castellsagué, N. Muñoz, J. M. Escribà, E. Hamsíkova, V. Hofmannova, et al. "Human papillomavirus DNA and antibodies to human papillomaviruses 16 E2, L2, and E7 peptides as predictors of survival in patients with squamous cell cervical cancer." Journal of Clinical Oncology 15, no. 2 (February 1997): 610–19. http://dx.doi.org/10.1200/jco.1997.15.2.610.
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PURPOSE To assess whether human papillomavirus (HPV) DNA detection in cervical cancer specimens, or antibodies to selected HPV 16 peptides are predictors of tumor recurrence and long-term survival in patients with squamous cell invasive cervical cancer. SUBJECTS AND METHODS Four hundred seventy-one cases included in two population-based case-control studies underwent follow-up evaluation. The survival and cause of death were ascertained for 410 cases (87%), with a median follow-up time of 4.6 years after diagnosis. HPV DNA was assessed using an L1 polymerase chain reaction (PCR)-based system and Southern hybridization (SH) on scraped cytologic specimens or biopsies. HPV 16 antibodies to E2, L2, and E7 peptides were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS Clinical stage was the only independent prognostic factor for recurrence or survival. Although seropositivity to HPV 16 E7/3 peptide predicted a twofold excess risk of mortality (adjusted hazards ratio [HRa] = 2.0; 95% confidence interval [CI], 1.2 to 3.3), the association was restricted to stage I (HRa = 6.6; 95% CI, 1.2 to 37.6) and II (HRa = 5.9; 95% CI, 2.1 to 16.5) patients. The presence of HPV DNA (HRa = 0.9; 95% CI, 0.5 to 1.5), different estimates of the HPV viral load and the HPV type identified were not predictors of tumor recurrence or survival. CONCLUSION The presence of antibodies to HPV 16 E7 proteins is of prognostic value in early-stage cervical cancer. Our results provide strong evidence that detection and typing of HPV DNA in cervical cells or tissues is not a prognostic factor for recurrence or survival.
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Oliveira, Walmar R., Gustavo N. Ferreira, Peter L. Rady, Cyro Festa, and Stephen K. Tyring. "Epidermodysplasia Verruciformis Associated with Myelodysplastic Syndrome: An Intriguing Association." Journal of Cutaneous Medicine and Surgery 13, no. 6 (November 2009): 317–20. http://dx.doi.org/10.2310/7750.2009.08049.
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Background: Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by massive infection with human papillomaviruses (HPVs) and development of skin cancer. Myelodysplastic syndromes (MDSs) are a group of chronic conditions that involve dysplastic hematopoiesis, peripheral blood cytopenias, and a high incidence of progression into leukemia. Methods: We describe the intriguing association of these two premalignant conditions (EV and MDS) in one patient. These diagnoses were confirmed by histopathologic examination and cytogenetic abnormalities of bone marrow cells. Results: The patient presented initially with clinical features typical of EV and impairment of cell-mediated immunity. In the skin lesions, HPVs 23 and 25 were identified by nested polymerase chain reaction. Six years later, he had recurrent episodes of mucosal bleeding with fever, weakness, and fatigue. At this time, severe refractory anemia and neutropenia were observed, and bone marrow smears showed hypercellularity with abnormal dysplastic megakaryocytes. The cytogenetic pattern showed abnormalities involving trisomy of chromosomes 8 and 21. The patient received a diagnosis of the indolent subtype of MDS. Conclusions: Through the observation of our patient and review of the literature, we hypothesized that the pathomechanisms, including the role of oncogenes and cytokines, are connected to the progression to malignancy in these settings.
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Starodubtseva, Natalia L., Vitaliy V. Chagovets, Maria E. Nekrasova, Niso M. Nazarova, Alisa O. Tokareva, Olga V. Bourmenskaya, Djamilja I. Attoeva, et al. "Shotgun Lipidomics for Differential Diagnosis of HPV-Associated Cervix Transformation." Metabolites 12, no. 6 (May 31, 2022): 503. http://dx.doi.org/10.3390/metabo12060503.
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A dramatic increase in cervical diseases associated with human papillomaviruses (HPV) in women of reproductive age has been observed over the past decades. An accurate differential diagnosis of the severity of сervical intraepithelial neoplasia and the choice of the optimal treatment requires the search for effective biomarkers with high diagnostic and prognostic value. The objective of this study was to introduce a method for rapid shotgun lipidomics to differentiate stages of HPV-associated cervix epithelium transformation. Tissue samples from 110 HPV-positive women with cervicitis (n = 30), low-grade squamous intraepithelial lesions (LSIL) (n = 30), high-grade squamous intraepithelial lesions (HSIL) (n = 30), and cervical cancers (n = 20) were obtained. The cervical epithelial tissue lipidome at different stages of cervix neoplastic transformation was studied by a shotgun label-free approach. It is based on electrospray ionization mass spectrometry (ESI-MS) data of a tissue extract. Lipidomic data were processed by the orthogonal projections to latent structures discriminant analysis (OPLS-DA) to build statistical models, differentiating stages of cervix transformation. Significant differences in the lipid profile between the lesion and surrounding tissues were revealed in chronic cervicitis, LSIL, HSIL, and cervical cancer. The lipids specific for HPV-induced cervical transformation mainly belong to glycerophospholipids: phosphatidylcholines, and phosphatidylethanolamines. The developed diagnostic OPLS-DA models were based on 23 marker lipids. More than 90% of these marker lipids positively correlated with the degree of cervix transformation. The algorithm was developed for the management of patients with HPV-associated diseases of the cervix, based on the panel of 23 lipids as a result. ESI-MS analysis of a lipid extract by direct injection through a loop, takes about 25 min (including preparation of the lipid extract), which is significantly less than the time required for the HPV test (several hours for hybrid capture and about an hour for PCR). This makes lipid mass spectrometric analysis a promising method for express diagnostics of HPV-associated neoplastic diseases of the cervix.
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Burd, Eileen M. "Human Papillomavirus Laboratory Testing: the Changing Paradigm." Clinical Microbiology Reviews 29, no. 2 (February 24, 2016): 291–319. http://dx.doi.org/10.1128/cmr.00013-15.
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SUMMARYHigh-risk human papillomaviruses (HPVs) cause essentially all cervical cancers, most anal and oropharyngeal cancers, and some vaginal, vulvar, and penile cancers. Improved understanding of the pathogenesis of infection and the availability of newer tests are changing the approach to screening and diagnosis. Molecular tests to detect DNA from the most common high-risk HPVs are FDA approved for use in conjunction with cytology in cervical cancer screening programs. More-specific tests that detect RNA from high-risk HPV types are now also available. The use of molecular tests as the primary screening tests is being adopted in some areas. Genotyping to identify HPV16 and -18 has a recommended role in triaging patients for colposcopy who are high-risk HPV positive but have normal cytology. There are currently no recommended screening methods for anal, vulvar, vaginal, penile, or oropharyngeal HPV infections. HPV testing has limited utility in patients at high risk for anal cancer, but p16 immunohistochemistry is recommended to clarify lesions in tissue biopsy specimens that show moderate dysplasia or precancer mimics. HPV testing is recommended for oropharyngeal squamous cell tumors as a prognostic indicator. Ongoing research will help to improve the content of future guidelines for screening and diagnostic testing.
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El Kettani, Assiya, Fatima Ailal, Jalila El Bakkouri, Khalid Zerouali, Vivien Béziat, Emmanuelle Jouanguy, Jean-Laurent Casanova, and Ahmed Aziz Bousfiha. "HPV-Related Skin Phenotypes in Patients with Inborn Errors of Immunity." Pathogens 11, no. 8 (July 29, 2022): 857. http://dx.doi.org/10.3390/pathogens11080857.
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Patients with inborn errors of immunity (IEI) are prone to develop infections, either due to a broad spectrum of pathogens or to only one microbe. Since skin is a major barrier tissue, cutaneous infections are among the most prevalent in patients with IEI due to high exposures to many microbes. In the general population, human papillomaviruses (HPVs) cause asymptomatic or self-healing infections, but, in patients with IEI, unusual clinical expression of HPV infection is observed ranging from epidermodysplasia verruciformis (EV) (a rare disease due to β-HPVs) to profuse, persistent, and recalcitrant warts (due to α-, γ-, and μ-HPVs) or even tree man syndrome (due to HPV2). Mutations in EVER1, EVER2, and CIB1 are associated with EV phenotype; GATA2, CXCR4, and DOCK8 mutations are typically associated with extensive HPV infections, but there are several other IEI that are less frequently associated with severe HPV lesions. In this review, we describe clinical, immunological, and genetic patterns of IEI related to severe HPV cutaneous infections and propose an algorithm for diagnosis of IEI with severe warts associated, or not, with lymphopenia.
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Acquaviva, Giorgia, Michela Visani, Viviana Sanza, Antonio De Leo, Thais Maloberti, Paola Pierotti, Paola Crucitti, et al. "Different Methods in HPV Genotyping of Anogenital and Oropharyngeal Lesions: Comparison between VisionArray® Technology, Next Generation Sequencing, and Hybrid Capture Assay." Journal of Molecular Pathology 2, no. 1 (March 4, 2021): 29–41. http://dx.doi.org/10.3390/jmp2010004.
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(1) Background: Human papillomaviruses (HPVs) are known to be related to the development of about 5% of all human cancers. The clinical relevance of HPV infection has been deeply investigated in carcinomas of the oropharyngeal area, uterine cervix, and anogenital area. To date, several different methods have been used for detecting HPV infection. The aim of the present study was to compare three different methods for the diagnosis of the presence of the HPV genome. (2) Methods: A total of 50 samples were analyzed. Twenty-five of them were tested using both next generation sequencing (NGS) and VisionArray® technology, the other 25 were tested using Hybrid Capture (HC) II assay and VisionArray® technology. (3) Results: A substantial agreement was obtained using NGS and VisionArray® (κ = 0.802), as well as between HC II and VisionArray® (κ = 0.606). In both analyses, the concordance increased if only high risk HPVs I(HR-HPVs) were considered as “positive”. (4) Conclusions: Our data highlighted the importance of technical choice in HPV characterization, which should be guided by the clinical aims, costs, starting material, and turnaround time for results.
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Kuma, Yuki, Takamichi Ito, Konosuke Nagae, Yukihiro Mizote, Takeshi Nakahara, Hiroshi Uchi, Yuichi Yamada, et al. "Two Cases of Cutaneous Squamous Cell Carcinoma Arising in Immunosuppressed Patients with Chronic Human Papillomavirus Infection." Case Reports in Dermatology 7, no. 2 (July 25, 2015): 178–82. http://dx.doi.org/10.1159/000438504.
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Increasing evidence has suggested that human papillomaviruses (HPVs) are linked to a large subset of numerous malignant tumors, including mucosal squamous cell carcinoma (SCC); however, its involvement in cutaneous SCC has not fully been elucidated. Cutaneous SCC is the second most common type of skin cancer and is increasing in frequency every year. Since we have no satisfactory treatment for advanced SCC, it is important to provide a definitive diagnosis and appropriate therapeutic intervention at an early stage. Here, we present two cases of SCC arising in immunosuppressed patients. In these cases, we suspected the association between SCC and HPV infection histopathologically and succeeded in proving the presence of high-risk type HPV by PCR analysis (HPV 14 in case 1 and HPV 23 and 38 in case 2). Although it is unclear whether HPV actually induced SCC in our cases, our cases showed rapid progression comparing to typical courses of actinic keratosis (AK)/SCC. SCC and AK are common diseases; in daily practice, dermatologists examine many patients with immunosuppression of various causes. We should apply increased oncological vigilance to these patients to prevent an aggressive course of SCC/AK.
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Skubic, Lucijan, Lea Hošnjak, Vesna Breznik, Kristina Fujs Komloš, Boštjan Luzar, and Mario Poljak. "An Improved Protocol for Comprehensive Etiological Characterization of Skin Warts and Determining Causative Human Papillomavirus Types in 128 Histologically Confirmed Common Warts." Viruses 14, no. 10 (October 15, 2022): 2266. http://dx.doi.org/10.3390/v14102266.
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Human papillomaviruses (HPVs) are etiologically associated with various benign and malignant neoplasms of cutaneous and mucosal epithelia. We describe an improved diagnostic protocol for comprehensive characterization of causative HPV types in common warts, in which broad-spectrum PCRs followed by Sanger sequencing, two previously described and seven newly developed type-specific quantitative real-time PCRs (qPCRs) coupled with the human beta-globin qPCR were used for: (i) diagnosis of HPV infection in warts; (ii) estimation of cellular viral loads of all HPV types detected; and (iii) determination of their etiological role in 128 histologically confirmed fresh-frozen common wart tissue samples. A total of 12 different causative HPV types were determined in 122/126 (96.8%) HPV-positive warts, with HPV27 being most prevalent (27.0%), followed by HPV57 (26.2%), HPV4 (15.1%), HPV2 (13.5%), and HPV65 (7.9%). The cellular viral loads of HPV4 and HPV65 were estimated for the first time in common warts and were significantly higher than the viral loads of HPV2, HPV27, and HPV57. In addition, we showed for the first time that HPV65 is etiologically associated with the development of common warts in significantly older patients than HPV27 and HPV57, whereas HPV4-induced warts were significantly smaller than warts caused by HPV2, HPV27, HPV57, and HPV65.
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Kobayashi, Kazuhiro, Kenji Hisamatsu, Natsuko Suzui, Akira Hara, Hiroyuki Tomita, and Tatsuhiko Miyazaki. "A Review of HPV-Related Head and Neck Cancer." Journal of Clinical Medicine 7, no. 9 (August 27, 2018): 241. http://dx.doi.org/10.3390/jcm7090241.
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Head and neck squamous cell carcinomas (HNSCCs) arise in the mucosal lining of the upper aerodigestive tract. Tobacco and alcohol use have been reported to be associated with HNSCC. Infection with high-risk human papillomaviruses (HPVs) has recently been implicated in the pathogenesis of HNSCCs. It is now widely accepted that high-risk HPV is a cause of almost all cervical cancers as well as some forms of HNSCCs. HPV-related HNSCCs are increasing. HPV-related HNSCCs and HPV-unrelated HNSCCs differ with respect to the molecular mechanisms underlying their oncogenic processes. HPV-related HNSCCs are known to have a better prognosis response to treatment as compared with HPV-unrelated HNSCCs. Therefore, in recent years, it has been required to accurately discriminate between HPV-related and HPV-unrelated HNSCCs. To diagnose the HPV-related HNSCCs, various methods including P16 immunohistochemistry, FISH, and genetic analyses of the HPV gene from histopathological and liquid biopsy specimens have been employed. Based on the results of the differential diagnosis, various treatments employing EGFR TKI and low-dose radiation have been employed. Here, we review the involvement of the HPV virus in HNSCCs as well as the molecular mechanism of carcinogenesis, classification, prognosis, diagnostic procedures, and therapy of the disease.
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Chawla, Jatinder Pal Singh, Nageshwar Iyer, Kanwaldeep Singh Soodan, Atul Sharma, Sunpreet Kaur Khurana, and Pratiksha Priyadarshni. "Role of miRNA in cancer diagnosis, prognosis, therapy and regulation of its expression by Epstein–Barr virus and human papillomaviruses: With special reference to oral cancer." Oral Oncology 51, no. 8 (August 2015): 731–37. http://dx.doi.org/10.1016/j.oraloncology.2015.05.008.
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Verachi, F., Z. Percario, P. Di Bonito, E. Affabris, C. Amici, and L. Accardi. "Purification and Characterization of Antibodies in Single-Chain Format against the E6 Oncoprotein of Human Papillomavirus Type 16." BioMed Research International 2018 (2018): 1–9. http://dx.doi.org/10.1155/2018/6583852.
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In Human Papillomaviruses- (HPV-) associated carcinogenesis, continuous expression of the E6 oncoprotein supports its value as a potential target for the development of diagnostics and therapeutics for HPV cancer. We previously reported that the I7 single-chain antibody fragment (scFv) specific for HPV16 E6, expressed as an intrabody by retroviral system, could inhibit significantly the growth of cervical cancer cells in vitro and was even able to reduce tumor development in experimental HPV-related cancer models. Nevertheless, for the development of therapeutic tools to be employed in humans, it is important to achieve maximum safety guarantee, which can be provided by the protein format. In the current study, two anti-16E6 scFvs derived from I7 were expressed in E. coli and purified in soluble form by affinity chromatography. Specificity, sensitivity and stability in physiologic environment of the purified scFvs were demonstrated by binding studies using recombinant 16E6 as an antigen. The scFvs functionality was confirmed by immunofluorescence in cervical cancer cells, where the scFvs were able to recognize the nuclear E6. Furthermore, an antiproliferative activity of the scFvI7nuc delivered in protein format to HPV16-positive cell lines was observed. Our results demonstrate that functional anti-16E6 scFvs can be produced in E. coli, suggesting that such purified antibodies could be used in the diagnosis and treatment of HPV-induced malignancies.
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Remschmidt, Cornelius, Andreas M. Kaufmann, Ingke Hagemann, Elena Vartazarova, Ole Wichmann, and Yvonne Deleré. "Risk Factors for Cervical Human Papillomavirus Infection and High-Grade Intraepithelial Lesion in Women Aged 20 to 31 Years in Germany." International Journal of Gynecologic Cancer 23, no. 3 (March 2013): 519–26. http://dx.doi.org/10.1097/igc.0b013e318285a4b2.
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BackgroundPersistent infection with high-risk human papillomaviruses (HPVs) can lead to cervical intraepithelial lesion and cervical cancer. Sexual behavior and smoking have been identified as risk factors for HPV infection. However, it is unclear which factors account for the persistence of HPV infection and for high-grade squamous intraepithelial lesions (HSIL). Therefore, we conducted a study to identify epidemiological risk factors for the following: (1) the presence of HPV among women without a recent diagnosis of HSIL and (2) HSIL.Materials and MethodsParticipants aged 20 to 31 years were recruited at 2 study sites. All women received a cervical Papanicolaou test, were tested for HPV, and categorized into 1 of 3 different groups: The women of the first group had negative cytological test results and a negative HPV test result (HPV-negative group), and the women of the second group had negative cytological test result but positive HPV test result (HPV-positive group). The third group consisted of women with a diagnosis of HSIL (HSIL group). We first compared the HPV-negative group with the HPV-positive group, and then the HPV-positive group with the HSIL group.ResultsOne hundred forty-seven women were included: 53 women in the HPV-negative group, 46 women in the HPV-positive group, and 48 women in the HSIL group. Comparing the HPV-negative with the HPV-positive group, we found that more than 5 sexual partners during a lifetime were independently associated with cervical HPV infection, whereas the chance of being infected decreased with older age. Irregular condom use during one-night stands or smoking was associated with HPV infection only in univariable but not multivariable analysis. In contrast, older age and having had genital warts were independently associated with an HSIL diagnosis when comparing the HPV-positive group with the HSIL group.DiscussionAlthough the study was hampered by its relatively small sample size, our data suggest that main risk factors for the acquisition of HPV infection are a higher number of sexual partners and younger age, whereas older age and genital warts may be epidemiological cofactors in the development of HSIL.
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Juang, Sin-Ei, Kevin Sheng-Kai Ma, Pei-En Kao, James Cheng-Chung Wei, Hei-Tung Yip, Mei-Chia Chou, Yao-Min Hung, and Ning-Chien Chin. "Human Papillomavirus Infection and the Risk of Erectile Dysfunction: A Nationwide Population-Based Matched Cohort Study." Journal of Personalized Medicine 12, no. 5 (April 27, 2022): 699. http://dx.doi.org/10.3390/jpm12050699.
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Background: Male patients with genital warts are known for higher rates of sexual dysfunction. This study was conducted to investigate whether human papillomaviruses (HPV) infection is associated with an increased risk of erectile dysfunction (ED). Methods: Patients aged over 18 with HPV infection (n = 13,296) and propensity score-matched controls (n = 53,184) were recruited from the Longitudinal Health Insurance Database (LHID). The primary endpoint was the diagnosis of ED. Chi-square tests were used to analyze the distribution of demographic characteristics. The Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the development of ED in both groups, after adjusting for sex, age, relevant comorbidities, co-medication, and surgery. Results: ED developed in 181 patients of the study group. The incidence density of ED was 2.53 per 1000 person-years for the HPV group and 1.51 per 1000 person-years for the non-HPV group, with an adjusted HR (95% CI) of 1.63 (1.37–1.94). In stratification analysis, adjusted HR of diabetes-, chronic obstructive pulmonary disease (COPD-), and stroke-subgroup were 2.39, 2.51, and 4.82, with significant p values for interaction, respectively. Sensitivity analysis yields consistent findings. Conclusions: The patients with HPV infection had a higher risk of subsequent ED in comparison to the non-HPV controls. The mechanism behind such association and its possible role in ED prevention deserves further study in the future.
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Catteau, Xavier, Philippe Simon, and Jean-Christophe Noël. "Evaluation of the Oncogenic Human Papillomavirus DNA Test with Liquid-Based Cytology in Primary Cervical Cancer Screening and the Importance of the ASC/SIL Ratio: A Belgian Study." ISRN Obstetrics and Gynecology 2014 (February 18, 2014): 1–5. http://dx.doi.org/10.1155/2014/536495.
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Objectives. In Belgium, very few studies have focused on cervical high-risk human papillomaviruses (hrHPV) prevalence and the relationship between HPV and cervical cytological abnormalities. The aim of this study was to investigate hrHPV prevalence and its relationship with cytological screening and histological results in the French-speaking community in Belgium (Brussels and Wallonia). Methods. A total of 58,265 liquid-based cytology tests were performed during this period. All cases of ASC-US, ASC-H, LSIL, and HSIL were tested by Hybrid Capture 2 for hrHPV screening. Results. The prevalence of cytological abnormalities was 3.1% for ASC-US, 0.3% for ASC-H, 1.5% for LSIL, and 0.3% for HSIL. The frequency of hrHPV infection was 47% in ASC-US, 90% in ASC-H, 86% in LSIL, and 98.4% in HSIL. CIN 2+ lesions were found in 12.2% of smears with an ASC-US result, in 54% of smears with an ASC-H result, in 12.5% of smears with a LSIL result, and in 89.3% of smears with a HSIL result. The ASC/SIL ratio was 1.9%. Conclusions. This study provides a good representation of cytological abnormalities and HPV status in patients living in Belgium’s French-speaking community. The prevalence in our study was similar to that derived from meta-analyses of European studies. Our ASC/SIL ratio was 1.9%, being within the lower and upper limits proposed in the literature, which tends to prove the good quality diagnosis of cervical smears in our laboratory.
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Tovo, Sessi Frida, Théodora Mahoukèdè Zohoncon, Amana Metuor Dabiré, Régine Ilboudo, Rahimatou Yasmine Tiemtoré, Dorcas Obiri-Yeboah, Albert Théophane Yonli, et al. "Molecular Epidemiology of Human Papillomaviruses, Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium among Female Sex Workers in Burkina Faso: Prevalence, Coinfections and Drug Resistance Genes." Tropical Medicine and Infectious Disease 6, no. 2 (May 27, 2021): 90. http://dx.doi.org/10.3390/tropicalmed6020090.
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Viral and bacterial infections represent an occupational risk for female sex workers. This study aimed at determining HPV coinfection with genital pathogens among female sex workers in West and Central Africa and identifying antibiotic resistance genes. A total of 182 samples from female sex workers were analyzed by real-time PCR and classic PCR. For the molecular diagnosis of HPV, the real-time multiplex amplification kit “HPV Genotypes 14 Real-TM Quant” from SACACE Biotechnologies®, detecting 14 high-risk HPV genotypes, was used, while for other pathogens, the real-time multiplex amplification kit N. gonorrhoeae/C. trachomatis/M. genitalium/T. vaginalis Real-TM, allowing their simultaneous detection, was used. The women were aged 17–50 years with an average age of 27.12 ± 6.09 years. The pathogens identified were HPV 54.94% (100/120), Neisseria gonorrhoeae (13.74%), Chlamydia trachomatis (11.54%) and Mycoplasma genitalium (11.54%). The most common HPV genotypes were HPV68, HPV38 and HPV52. The antibiotic resistance genes identified were bla QNR B 24.00%, bla GES 22.00%, bla SHV 17.00%, blaCTX-M 13.00% and bla QNR S 1.00%. This study revealed the presence of various HPV genotypes associated with other pathogens with problems of antibiotic resistance among sex workers of West and Central African origin working in Ouagadougou.
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Alkhilaiwi, Faris, and Hang Yuan. "Detection of HPV RNA in Extracellular Vesicles from Neuroendocrine Cervical Cancer Cells." Viruses 14, no. 10 (October 10, 2022): 2226. http://dx.doi.org/10.3390/v14102226.
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Background: Neuroendocrine carcinoma of the cervix (NECC) is an aggressive and rare type of cervical cancer. The five-year overall survival is low at 30% and there is no standardized therapy based on controlled trials for this type of tumour. Most are locally advanced or metastasized at the time of the diagnosis. Extracellular vesicles (EVs) could be a carrier of viral DNA/RNA, given their vital role in cellular communication. The content of EV derived from NECC cells has not been investigated due to the lack of cell line, and it is not known whether they contain human papillomaviruses (HPV) DNA/RNA or not. Methods: The presence of viral E7 DNA/RNA in EVs purified from a culture of a recently established NECC cell line, GUMC-395, was evaluated by using droplet digital polymerase chain reaction (ddPCR). These EVs were characterized using nanoparticle tracking analysis (NTA) for size distribution, transmission electron microscopy (TEM) for morphology, Western blot for CD63, and bioanalyser for RNA quantity and quality. Results: HPV16 viral-RNA, but not DNA, was detected in EVs from GUMC-395 using ddPCR. NTA identified EVs with a mean diameter of 105.0 nm, TEM confirmed normal morphological shape and size, and Western blot analysis confirmed the presence of EV-associated proteins CD63. The EVs were found to be enriched with small RNAs using a bioanalyser. Conclusions: HPV16 RNA is found in EVs from a neuroendocrine cervical cancer and could be involved in the pathogenesis of the disease and used as a diagnostic biomarker.
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Ahmadi, Maryam, Farid Azizi Jalilian, Negar Dokhani, Mitra Golparian, and Younes Moradi. "Evaluation of the Prevalence of Human Papillomavirus in Asymptomatic Patients at the Women’s Clinic in Hamadan and Comparing the 2 Methods of Pap Smear and PCR in Detecting the Virus." International Journal of Women's Health and Reproduction Sciences 8, no. 2 (February 6, 2020): 232–35. http://dx.doi.org/10.15296/ijwhr.2020.37.
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Objectives: Human papillomaviruses (HPVs) are a group of non-enveloped viruses which contain double-stranded DNA, and have widespread prevalence in human populations. The aim of this study was to evaluate the prevalence of HPV in asymptomatic patients at the Women’s Clinic in Hamadan and compare the two techniques of Pap smear and Polymerase chain reaction (PCR) in detecting the virus. Materials and Methods: This epidemiologic study was carried out on 1770 asymptomatic patients at the Women’s Clinic in Hamadan. After collecting the cell samples from the cervical areas, they were placed in a pre-prepared medium by a physician and divided into two sections after being sent to the laboratory; the first part was for Pap smear and the second for PCR. If there was a viral genome, it could be determined by PCR. People who were HPV + were candidates for typing. Results: The results of the present study showed that out of 1770 patients aged between 14 and 60 years, referred to Hamadan health centers, 271 patients (15.31%) had HPV. Among them, the highest number of HPV+ cases belonged to the age group of 31-40 years, with the lowest number belonging to the age group of 15-20 years old. Furthermore, out of 271 HPV + patients, 111 (40.09%) had abnormal Pap smear and more than 90% had HPV infection, while less than 10% had low risk (LR) HPV. Conclusions: The results of this study showed that the prevalence of HPV in Hamadan health centers was relatively high. According to the results of this study, it can be concluded that the use of PCR along with Pap smear can help the patients with diagnosis and better treatment.
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Speich, Norbert, Christoph Schmitt, Reinhard Bollmann, and Magdolna Bollmann. "Human papillomavirus (HPV) study of 2916 cytological samples by PCR and DNA sequencing: genotype spectrum of patients from the west German area." Journal of Medical Microbiology 53, no. 2 (February 1, 2004): 125–28. http://dx.doi.org/10.1099/jmm.0.05447-0.
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Human papillomaviruses (HPVs) are aetiological agents for cervical cancer. More than 70 different HPV types that infect genital mucosa have been found. In order to develop a sensitive and specific detection and typing assay, a PCR/direct sequencing approach was used. Two pairs of consensus primers were used for amplification of HPV DNA and the PCR products obtained were analysed by automated sequencing. Sequences were compared with those in GenBank by using the blast program. In this study, 2916 cytological samples were screened for HPV, as well as for triage. Nine hundred and forty-eight (32.5 %) samples were positive for HPV, of which 134 harboured more than one HPV type. Of the 948 PCR-positive samples, 648 were typed. Thirty-nine different HPV types were identified by sequencing. The two most frequently found HPV types, 16 and 31, together accounted for 36.3 % of the sequences (26.2 and 10.1 %, respectively). This group was followed by HPV types 6 (5.7 %), 18 (5.3 %), 58 (4.5 %), 61 (4.5 %), 53 (4.4 %), 42 (4.3 %) and 51 (4.0 %). All other types were detected at frequencies <4 % and eight types were detected only once. PCR/direct sequencing is a reliable method for routine detection of HPV in cytological samples. The data presented here suggest a complex distribution of HPV types in the population tested. The results accentuate the importance of PCR-based techniques in HPV diagnosis, as hybridization-based methods can only detect a limited number of infections. This method can also be applied easily to the analysis of tissue samples and it therefore also allows type-specific follow-up of women who have been treated for cervical intraepithelial neoplasia.
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Liang, Winnie S., Jessica Aldrich, Sara Nasser, Ahmet Kurdoglu, Lori Phillips, Rebecca Reiman, Jacquelyn McDonald, et al. "Simultaneous Characterization of Somatic Events and HPV-18 Integration in a Metastatic Cervical Carcinoma Patient Using DNA and RNA Sequencing." International Journal of Gynecologic Cancer 24, no. 2 (February 2014): 329–38. http://dx.doi.org/10.1097/igc.0000000000000049.
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ObjectiveIntegration of carcinogenic human papillomaviruses (HPVs) into the host genome is a significant tumorigenic factor in specific cancers including cervical carcinoma. Although major strides have been made with respect to HPV diagnosis and prevention, identification and development of efficacious treatments for cervical cancer patients remains a goal and thus requires additional detailed characterization of both somatic events and HPV integration. Given this need, the goal of this study was to use the next generation sequencing to simultaneously evaluate somatic alterations and expression changes in a patient’s cervical squamous carcinoma lesion metastatic to the lung and to detect and analyze HPV infection in the same sample.Materials and MethodsWe performed tumor and normal exome, tumor and normal shallow whole-genome sequencing, and RNA sequencing of the patient’s lung metastasis.ResultsWe generated over 1.2 billion mapped reads and identified 130 somatic point mutations and indels, 21 genic translocations, 16 coding regions demonstrating copy number changes, and over 36 genes demonstrating altered expression in the tumor (correctedP< 0.05). Sequencing also revealed the HPV type 18 (HPV-18) integration in the metastasis. Using both DNA and RNA reads, we pinpointed 3 major events indicating HPV-18 integration into an intronic region of chromosome 6p25.1 in the patient’s tumor and validated these events with Sanger sequencing. This integration site has not been reported for HPV-18.ConclusionsWe demonstrate that DNA and RNA sequencing can be used to concurrently characterize somatic alterations and expression changes in a biopsy and delineate HPV integration at base resolution in cervical cancer. Further sequencing will allow us to better understand the molecular basis of cervical cancer pathogenesis.
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Voidăzan, Septimiu Toader, Caterina Dianzani, Mădălina Aurelia Husariu, Bíborka Geréd, Sabin Gligore Turdean, Cosmina Cristina Uzun, Zsolt Kovacs, Florin Francisc Rozsnyai, and Nicoleta Neagu. "The Role of p16/ Ki-67 Immunostaining, hTERC Amplification and Fibronectin in Predicting Cervical Cancer Progression: A Systematic Review." Biology 11, no. 7 (June 23, 2022): 956. http://dx.doi.org/10.3390/biology11070956.
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Human papillomaviruses (HPVs) are common sexually transmitted infectious agents responsible for several anogenital and head and neck cancers. Cervical cancer (CC) is the fourth leading cause of death in women with cancer. The progression of a persistent HPV infection to cancer takes 15–20 years and can be preventable through screening. Cervical cytology (Pap smear) is the standard screening test for CC and precancerous lesions. For ASC-US and ASC-H lesions, a combination of Pap smear and HR-HPV analysis is recommended as a triage step before colposcopy. However, these tests cannot predict progression to CC. For this purpose, we summarized current scientific data on the role of p16/Ki-67 immunohistostaining, telomerase and fibronectin in predicting progression to CC. p16 and p16/Ki-67 dual staining (DS) were more specific than HR-HPV DNA testing for the detection of CIN2+/CIN3+ in women with ASC-US and LSIL. Similarly, hTERC FISH analysis significantly improved the specificity and positive predictive value of HPV DNA testing in differentiating CIN2+ from CIN2 cytological samples. In conclusion, p16 IHC, p16/Ki-67 DS and hTERC FISH amplification are all valid adjunctive biomarkers which significantly increase the sensitivity and specificity of cervical dysplasia diagnosis, especially when combined with HPV DNA testing. However, considering the global socioeconomic background, we can postulate that p16 and p16/ Ki-67 IHC can be used as a next step after positive cytology for ASC-US or LSIL specimens in low-income countries, instead of HPV DNA testing. Alternatively, if HPV DNA testing is covered by insurance, p16 or p16/Ki-67 DS and HPV DNA co-testing can be performed. In middle- and high-income countries, hTERC amplification can be performed as an adjunctive test to HPV DNA testing in women with ASC-US and LSIL.
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Camus, Claire, Sébastien Vitale, Céline Loubatier, Guillaume Pénaranda, Hacène Khiri, Anne Plauzolles, Xavier Carcopino, Philippe Halfon, and Valérie Giordanengo. "Quantification of HPV16 E6/E7 mRNA Spliced Isoforms Viral Load as a Novel Diagnostic Tool for Improving Cervical Cancer Screening." Journal of Clinical Medicine 7, no. 12 (December 8, 2018): 530. http://dx.doi.org/10.3390/jcm7120530.
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High-risk human papillomaviruses (HPVs) have been identified as the main contributors to cervical cancer. Despite various diagnostic tools available, including the predominant Papanicolaou test (Pap test), technical limitations affect the efficiency of cervical cancer screening. The aim of this study was to evaluate the diagnostic performance of spliced HPV16 E6/E7 mRNA viral loads (VL) for grade 2 or higher cervical intraepithelial neoplasia diagnosis. A new dedicated (quantitative reverse transcription polymerase chain reaction) qRT-PCR assay was developed, allowing selective quantification of several HPV16 E6/E7 mRNA: Full length (FL) with or without all or selected spliced forms (total E6/E7 mRNA corresponding to SP + E6^E7 mRNA (T), + spliced E6/E7 mRNA containing intact E7 ORF (SP), and E6/E7 mRNA containing disrupted E6 and E7 ORFs calculated by the following subtraction T-SP (E6^E7)). Twenty HPV16 DNA and mRNA positive uterine cervical smears representative of all cytological and histological stages of severity were tested. We have shown that all E6/E7 mRNA isoforms expression levels were significantly increased in high grade cervical lesions. Statistical analysis demonstrated that the SP-E6/E7 VL assay exhibited: (i) The best diagnostic performance for identification of both cervical intraepithelial neoplasia (CIN)2+ (90% (56–100) sensitivity and specificity) and CIN3+ (100% (72–100) sensitivity and 79% (49–95) specificity) lesions; (ii) a greater sensitivity compared to the Pap test for CIN2+ lesions detection (80% (44–97)); (iii) a predictive value of the histological grade of cervical lesions in 67% of atypical squamous cells of unknown significance (ASC-US) and 100% of low-grade (LSIL) patients. Overall, these results highlight the value of SP-E6/E7 mRNA VL as an innovative tool for improving cervical cancer screening.
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Sun, Zhengrong, Gaowei Ren, Xin Cui, Weiqiang Zhou, Chao Liu, and Qiang Ruan. "Genetic Diversity of HPV-16E6,E7, andL1Genes in Women With Cervical Lesions in Liaoning Province, China." International Journal of Gynecologic Cancer 21, no. 3 (April 2011): 551–58. http://dx.doi.org/10.1097/igc.0b013e3182112023.
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IntroductionHigh-risk human papillomaviruses (HPVs) play a cardinal role in the etiology of cervical cancer. The most prevalent type, HPV-16, shows intratypic sequence variants that are known to differ in oncogenic potential and geographic distribution. Intratype variations in oncogenic E6/E7 and capsid L1 proteins of HPV-16 are associated with risk of viral persistence and progression.MethodsThis study was designed to analyze sequence variations inE6,E7, andL1genes of HPV-16 in patients with cervical lesion to identify the most prevalent and novel HPV-16 variants in northern China.ResultsOur results showed that HPV-16 variants with respect to E6 and E7 were high prevalence of the Asian lineage: 48.3% and 51.4%, respectively. Sequences of theE6gene revealed 4 amino acid changes of variants D25E and L83V, with 48.3% (69/143) and 11.2% (16/143), respectively, and variants H78Y and E113D in this study. The results also showed the prevalence of 4 hot spots of E7 nucleotide variations leading to N29H, N29S, and 2 silent variations, nucleotide G666A and nucleotide T846C, with 4.2% (6/142), 43% (61/142), 32.4% (46/142), and 43% (61/142), respectively. The following L1 variations were found in this study: L103F, P104K, P104Y, P104S, D105G, P106S, N108P, F109V, C172S, H228D, and T292A. It was also found that 448S was inserted and 465D was deleted in the L1 amino acid sequences of all the samples. No significant relationship between HPV-16 variants and high-grade lesions was found.ConclusionsThe study provides some new data on the genetic diversity of HPV-16, which may help to understand the oncogenic potential of the virus and design the diagnosis reagents and vaccine of HPV in China. Furthermore, in-depth studies are needed to determine the clinical and biological effects of these variants.
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Wyndham-West, Michelle, Nancy Durand, and Aimee Santoro. "Betwixt and Between Well and Sick in Cervical Precancer: Canadian Women’s Experiences of Recurring HPV Infections and HPV Vaccination." Canadian Journal of Nursing Research 50, no. 3 (May 14, 2018): 120–32. http://dx.doi.org/10.1177/0844562118763496.
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Background This research fuses the experiences of a precancer diagnosis with the decision-making surrounding a vaccine that can protect against human papillomavirus strains that women may not have been exposed to. The interviewee cohort is of note as half the women were in their 30s and 40s and 75% were over the age of 26. These groupings are often overlooked in media discourses and narrative research surrounding human papillomavirus and the human papillomavirus vaccine. Purpose Womens’ diagnoses and treatment experiences, including colposcopies, biopsies, and Loop Electrosurgical Excision Procedures, are chronicled to highlight a liminal, precancerous state—one in which they are not deemed healthy, but nor have they been diagnosed with cancer. These are emotion-filled experiences that are ridden with anxiety and fear, but also ones that are structured with self-care strategies to contain human papillomavirus infections and the risk of cervical cancer. Methods Twenty women who attended Sunnybrook Health Sciences Centre’s human papillomavirus vaccination clinic were interviewed and their narratives were documented and analyzed to determine their experiences surrounding human papillomavirus infections and precancer as well as their motivations for human papillomavirus vaccination. Results The decision to undergo human papillomavirus vaccination was a self-care strategy that accompanied treatment procedures and was a means to reduce cervical cancer risk. While encouraged with the human papillomavirus vaccine’s potential to curb cervical cancer, they had a tempered view of the vaccine and its effectiveness in their cases, given their medical histories. Conclusions The research provides an in-depth accounting of an often overlooked grouping in human papillomavirus and human papillomavirus vaccination research and media discourse which, generally, focuses upon middle-school-aged girls and university-/college-aged women. In addition, the research provides recommendations for practice for cervical precancer diagnoses going forward.
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Kattoor, Jayasree, and Meherbano M. Kamal. "The gray zone squamous lesions: ASC-US / ASC-H." Cytojournal 19 (April 30, 2022): 30. http://dx.doi.org/10.25259/cmas_03_10_2021.
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The unequivocal and easily recognizable entities of LSIL and HSIL pose no diagnostic problems for a trained eye. However, when the defining morphologic features are either qualitatively or quantitatively insufficient, it is then that the borderline category of “Atypical Squamous cells” (ASC) may have to be used. Scant and suboptimal preparations (mainly in conventional smears) are the common causes that hinder confident decision-making. The binary classification of the ASC category has been retained in The Bethesda System 2014. It includes ASC of undetermined significance (ASC-US) when the atypia is seen in mature cells and ASC-cannot rule out high-grade lesion (ASC-H) when borderline changes are seen in less mature, smaller metaplastic cells or smaller basaloid cells. There are many criticisms of the ASC category. The major one is its subjective and inconsistent applications and the low interobserver and intraobserver reproducibility. However, studies have shown that if we eliminate ASC-US, the LSIL rate will increase. If ASC-H is eliminated, the chances of detecting true lesions are reduced. Hence, there are strong reasons to retain the ASC category. The usual problems leading to the categorization of such cells as atypical are hyperchromasia beyond that acceptable as reactive change; abnormal chromatin pattern that is not overt dyskaryosis; minor variations in nuclear shape; and membrane outlines. Qualifying the atypical cells precisely in one of the categories has bearing on the clinical management and follow-up of the patient. Surveillance of women under the ASC-US category is either by repeat smear at 6 months and 1 year or by reflex human papillomaviruses DNA testing. Women with a Pap smear interpretation of ASC-H are directed to undergo immediate colposcopy. This article describes in detail the morphologic features of the ASC category, doubts about the correct interpretation of the chromatin pattern of the cells in question, and the differential diagnosis between normal, reactive, or inflammatory conditions, and LSIL/HSIL.
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Alifaga Muslimova, Sevda, Nushaba Fizuli Alishova, Ilhama Malik Karimova, and Raida Shamsaddin Vazirova. "PAPILLOMAVIRUS INFECTION AND CERVICAL PATHOLOGY." SCIENTIFIC WORK 74, no. 1 (January 17, 2022): 63–67. http://dx.doi.org/10.36719/2663-4619/74/63-67.
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Papillomavirus infection is one of the most common sexually transmitted infections. The aim of the study was to study the etiologic significance of the papillomavirus infection in the development of background diseases of the cervix and neoplasia. Under observation were 62 patients aged 18 to 55 years infected with human papillomavirus. All patients underwent complex clinical and anamnestic, laboratory and instrumental examination. Also, a review and advanced colposcopy was performed. As a result of the study, 53 (85.4%) women under observation were found to have various pathologies of the cervix. Dysplasia of mild degree (CIN 1 degree) was found in 12 (57.1%), moderate dysplasia (CIN 2 degree) - in 9 (42.9%) women. With further examination, it was found that patients along with dysplasia of varying severity had concomitant pathology of the cervix uteri. Cervical dysplasia was most often diagnosed in combination with another pathology of the cervix, which accounted for 85.7% of cases. It has been established that squamous epithelial lesion of the cervix is most often a consequence of late diagnosis and an untreated background process. At the same time, modern diagnostics requires a whole range of diagnostic measures to establish a diagnosis in the early stages of development and conduct differential diagnosis of a benign or malignant process. Key words: papillomavirus infection, cervix, colposcopy Sevda Alifaga Muslimova Nushaba Fizuli Alishova Ilhama Malik Karimova Raida Vazirova Xülasə Papillomavirus infeksiyası cinsi yolla keçən infeksiyalardan biridir. Tədqiqatın məqsədi uşaqlıq boynu və neoplaziyanın fon xəstəliklərinin inkişafında papillomavirus infeksiyasının etioloji əhəmiyyətini öyrənmək idi. İnsan papillomavirusuna yoluxmuş 18 yaşdan 55 yaşa qədər 62 xəstə müşahidə altında olub. Bütün xəstələr kompleks klinik və anamnestik, laboratoriya və instrumental müayinədən keçdilər. Həmçinin, baxış və təkmil kolposkopiya aparıldı. Araşdırma nəticəsində müşahidə altında olan 53 (85,4%) qadında uşaqlıq boynunun müxtəlif patologiyaları aşkar edilib. Yüngül dərəcəli displaziya (CIN 1 dərəcə) 12 (57,1%), orta displaziya (CIN 2 dərəcə) - 9 müayinədə müxtəlif şiddətli displaziya ilə birlikdə xəstələrdə uşaqlıq boynunun müşayiət olunan patologiyası aşkar edilmişdir. Servikal displaziya ən çox serviksin başqa patologiyası ilə birlikdə diaqnoz qoyuldu ki, bu da qadınların 85,7%-ni (42,9%) təşkil edirdi. Əlavə hallarla. Müəyyən edilmişdir ki, uşaqlıq boynunun skuamöz epiteliya zədələnməsi çox vaxt gec diaqnozun və müalicə olunmamış fon prosesinin nəticəsidir. Eyni zamanda, müasir diaqnostika inkişafın erkən mərhələlərində diaqnoz qoymaq və yaxşı və ya bədxassəli prosesin differensial diaqnostikasını aparmaq üçün bütün diaqnostik tədbirlərin həyata keçirilməsini tələb edir. Açar sözlər: papillomavirus infeksiyası, uşaqlıq boynu, kolposkopiya