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1
Cong, Duanduan. "Identification of functional single nucleotide polymorphisms (SNPs) in High Risk-Human Papillomavirus (HR-HPV) related diseases." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31174.
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Persistent infection of the cervix with high risk (HR) types of Human Papilloma Virus (HPV) (HR-HPV) can result in precancerous lesions and cancers. However, most HPV infections can be cleared naturally by the immune response without causing disease. Although genetic variations have long been considered as the main explanation for individual heterogeneity in cancer susceptibility, the underlying mechanisms remain unclear. In this project, a panel of routinely taken clinical samples was assessed for 32 rationally selected SNPs with allele frequency related to disease outcome using the Taqman® OpenArray® system. The panel incorporated 475 HR-HPV negative, cytologically-normal cervical samples, 413 HR-HPV positive cervical high grade squamous intraepithelial lesion (HSIL) cases and 62 HR-HPV positive cervical cancers. Two SNPs, rs2234671 and rs2623047, were found with significant differences between HR-HPV negative, cytologically-normal samples and HR-HPV positive cervical HSIL cases. In the validation step, these two SNPs were further genotyped in the same set of samples using TaqMan® SNP genotyping assay and/or LightSNiP assay and in additional samples including 83 HR-HPV positive, cytologically-normal cervical samples, 21 HR-HPV positive cervical cancer cases, 129 HR-HPV positive vulval intraepithelial neoplasia cases and 23 HR-HPV positive vulval cancer cases. Statistical analysis was then performed based on pooled and re-grouped genotyping data of the above-mentioned samples under different genetic models so as to evaluate the associations with different stages in the disease process. After validation, SULF1 rs2623047 revealed a strong significant association with the susceptibility to HR-HPV infection but not with the development of high-grade squamous intraepithelial lesion and the progression to cervical cancer. CXCR1 rs2234671, by contrast, was associated with the progression of HR-HPV-related cancers and the minor allele CXCR1 827C was significantly enriched in HPV16 positive cancers. CXCR1 is a receptor for the chemokine CXCL8/IL-8 and CXCR1 rs2234671 leads to a serine to threonine change in an extracellular loop of the receptor. Functionally, the CXCR1 827C allele was shown to enhance cell motility in response to IL-8 stimulation in a chemotaxis assay with transiently transfected fibroblasts (HEK293 cells) and also in a wound healing assay with stably transduced cervical cancer (CaSki) cells. In addition, significantly increased cell proliferation upon IL-8 treatment was observed in two cervical cancer derived cell lines, CaSki and SiHa, transduced with CXCR1-827C allele, but not in their CXCR1 827G transduced counterparts. These findings suggest that SULF1 rs2623047 and CXCR1 rs2234671 may be genetic risk factors for HR-HPV-related cervical disease and CXCR1 rs2234671 might affect HR-HPV-related cancer susceptibility by functionally altering IL-8-CXCR1 signalling. This information has potential for use in the risk stratification of HR-HPV infected women and may also suggest new therapeutic targets to be exploited for treatment of cervical cancer patients.
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Afrogheh, Amir. "The role of high-risk human papillomavirus in periocular cancers." University of the Western Cape, 2018. http://hdl.handle.net/11394/6554.
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Philosophiae Doctor - PhDPURPOSE: High risk human papillomavirus (HR-HPV) is well established as a causative agent of squamous cell carcinoma (SCC) of the orophaynx. HR-HPV has also been reported in periocular cancers and precancers, but controversy exists about its overall incidence and clinicopathologic profile. The purpose of this study is to evaluate the role of HR-HPV infection in periocular cancers and precancers, using multiple methods of detection. DESIGN: Retrospective observational case series with laboratory investigations. METHODS: Sequential surgical samples of 87 carcinomas (invasive SCC, SCC in situ and sebaceous carcinoma) from three different periocular sites (conjunctiva, lacrimal sac and the eyelid) diagnosed over a 15-year period (2000-2015) were selected for evaluation. Unstained paraffin sections of 87 cases of periocular carcinomas were analyzed with immunohistochemistry (IHC) for p16 as a screening test. p16 positive conjunctival- and lacrimal sac SCC were further evaluated for HR-HPV using DNA in situ hybridization (DNA ISH), and a subset was also analyzed by DNA Polymerase Chain Reaction (DNA PCR). p16 positive periocular sebaceous carcinomas (SC) were analyzed with PCR, and a subset of 18cases was further studied with a novel method of mRNA ISH, an advanced technique with an enhanced sensitivity and specificity. Relevant patient clinical information was obtained from review of the electronic medical records.
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Afrogheh, Amir H. "The role of high-risk human papillomavirus in periocular cancers." University of the Western Cape, 2018. http://hdl.handle.net/11394/6528.
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Philosophiae Doctor - PhDPurpose: High risk human papillomavirus (HR-HPV) is well established as a causative agent of squamous cell carcinoma (SCC) of the orophaynx. HR-HPV has also been reported in periocular cancers and precancers, but controversy exists about its overall incidence and clinicopathologic profile. The purpose of this study is to evaluate the role of HR-HPV infection in periocular cancers and precancers, using multiple methods of detection. Design: Retrospective observational case series with laboratory investigations. Methods: Sequential surgical samples of 87 carcinomas (invasive SCC, SCC in situ and sebaceous carcinoma) from three different periocular sites (conjunctiva, lacrimal sac and the eyelid) diagnosed over a 15-year period (2000-2015) were selected for evaluation. Unstained paraffin sections of 87 cases of periocular carcinomas were analyzed with immunohistochemistry (IHC) for p16 as a screening test. p16 positive conjunctival- and lacrimal sac SCC were further evaluated for HR-HPV using DNA in situ hybridization (DNA ISH), and a subset was also analyzed by DNA Polymerase Chain Reaction (DNA PCR). p16 positive periocular sebaceous carcinomas (SC) were analyzed with PCR, and a subset of 18cases was further studied with a novel method of mRNA ISH, an advanced technique with an enhanced sensitivity and specificity. Relevant patient clinical information was obtained from review of the electronic medical records.
4
Eldakhakhny, Sahar. "Crosstalk between high-risk human papillomavirus E7 and p63 in cervical cancer." Thesis, University of Manchester, 2018. https://www.research.manchester.ac.uk/portal/en/theses/crosstalk-between-highrisk-human-papillomavirus-e7-and-p63-in-cervical-cancer(105b5422-2ef0-40a8-9209-0d1d89fb75c9).html.
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Introduction: Cervical cancer is the fourth most common malignancy diagnosed in women worldwide. It results from cellular transformation by the high-risk human papillomavirus (HPV) oncogenes E6 and E7, which accounts for more than 99% of diagnosed cases. HPV links its life cycle to epithelial proliferation and differentiation, which requires the cells to remain active in cell cycle. p63 modulates epithelial development as well as proliferation, differentiation and DNA damage response (DDR), which makes it an important target for HPV oncoproteins to allow viral replication and survival in infected cells. Methods: In this study, small interfering RNAs targeting E7 oncoprotein and p63 in the HPV16 positive cervical cancer cell line CaSki were used. Western blotting, proliferation assays, apoptosis assays and cell cycle analysis were applied to examine the effects of E7 and p63 depletion on cell fate. Overexpression of different types of HPV-E7 was performed in the N/Tert-1 keratinocyte cell line to study the effect of E7 overexpression on p63 level. Results: E7 drives the expression of p63 at both transcript and protein levels in cervical cancer cell lines. Downregulation of E7 is accompanied by a remarkable inhibition of cell proliferation and cell cycle arrest in the G0/G1 phase. Depletion of E7 is associated with a significant reduction in p63 expression which is not due to impaired proliferation or induced differentiation. Downregulation of p63 is associated with delayed DDR in cervical cancer cells following treatment with ionising radiation. High-risk HPV E7s are more potent in inducing p63 upregulation and increasing the proliferation rates in keratinocytes. Conclusion: This work for the first time demonstrated that E7 modulates the expression of p63, which regulates DNA damage repair pathways, that promotes efficient and rapid repair of the DNA damage following ionising radiation treatment in cervical cancer cells. Tumour recurrence due to resistance to radiotherapy is common, mostly due to promoted DNA repair ability of cancer cells to reduce radiation-induced toxicity and increase cell survival in response to ionising radiation. These findings might be the key to the development of radioresistance in cervical cancer. The HPV E7-p63 axis may be a novel therapeutic target to enhance radio-sensitivity in HPV-transformed tumours.
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Dreilich, Martin, Michael Bergqvist, Martin Moberg, Daniel Brattström, Inger Gustavsson, Stefan Bergström, Alkwin Wanders, Patrik Hesselius, Gunnar Wagenius, and Ulf Gyllensten. "High-risk human papilloma virus (HPV) and survival in patients with esophageal carcinoma : a pilot study." Uppsala universitet, Institutionen för onkologi, radiologi och klinisk immunologi, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-94408.
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BACKGROUND: Human papilloma virus (HPV) in patients with esophageal carcinoma has previously been studied with an average detection rate of 15%, but the role of HPV in relation to survival is less clear. In cervical cancer, lung cancer and tonsil cancer HPV viral load is a predictive factor for survival and outcome of treatment. The primary aim was to study the spectrum of high-risk HPV types in esophageal tumors. Secondary, as a pilot study we investigated the association between HPV status and the survival rates. METHODS: We compared both the presence and the viral load of high-risk HPV types 16, 18, 31, 33, 39, 45, 52, 58, and 67 in relation to clinical data from patients with esophageal carcinoma. Survival data and tumor samples were retrieved from 100 patients receiving treatment at the Department of Oncology, Uppsala Hospital, Uppsala, Sweden. The tumor samples were investigated for HPV viral load using real-time PCR. RESULTS: HPV 16 was detected in 16% of the patients; no other HPV type was detected. HPV 16 infection had no significant effect on survival (p = 0.72). Also, HPV 16 did not improve survival after treatment (radiotherapy or chemotherapy). CONCLUSION: Only HPV 16 was detected among the patients. HPV 16 in esophageal carcinoma patients did not influence survival or improve therapy response. However, given the size of the study there is a need to examine a larger cohort in order to understand in more detail the effect of high risk HPV types in esophageal carcinoma.De två första författarna delar förstaförfattarskapet.
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Johnson, Derek Christopher. "Prevalence and determinants of high risk human papillomavirus (HPV) among wives of migrant workers -- A study in Far-West Nepal." Thesis, The University of Alabama at Birmingham, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=3719210.
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This dissertation research focuses on the risk factors associated with high-risk HPV infection (HR-HPV) and abnormal cervical cytology in Nepali women residing in Nepal’s Far-West district of Achham. The first part of this dissertation assesses the HR-HPV test concordance of self-collected vs. clinician-collected cervico-vaginal specimens. Of 261 women with both clinician- and self-collected cervical samples, 25 tested positive for HR-HPV, resulting in an overall HR-HPV prevalence of 9.6% (95% Confidence Interval [CI]: 6.3–13.8). The overall Kappa value for clinician- and self-collected tests was 0.64 (95% CI: 0.48–0.84), indicating a “good” level of agreement. The second part of this dissertation investigates the association between 251 women whose husband’s migrate for work and their high-risk HPV (HR-HPV) infection status and their abnormal cervical cytology status. Half of study participants (50.8%) had husbands who reported migrating for work at least once. Women 34 years and younger were significantly less likely to test positive for HR-HPV than women older than 34 years (OR 0.22, 95% CI 0.07–0.71). HR-HPV infection and abnormal cervical cytology status were not directly associated with a husband’s migration. The last part of this dissertation investigates the link between rates of sexually transmitted disease (STD) symptoms and geospatial differences among migrant workers using the Nepal Demographic Health Survey (NDHS). Data was restricted to 9,607 married women in the 2011 NDHS. Multivariate logistic regression models assessing the odds of reporting STD symptoms in the 2011 NDHS found that women whose husbands migrated for a year or more were more likely to report STD symptoms than women whose husbands were not currently migrating for work if they lived in Nepal’s Mid-West region (OR 1.93 95%CI 1.02–3.67) or Nepal’s Far-West region (OR 2.89 95%CI 1.24–6.73). The burden of increased risk factors for HR-HPV infection and abnormal cervical cytology could result in increases in HPV prevalence in the wives of Nepali migrant workers.
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O'Keefe, Elissa J., and n/a. "Young, sexually active, senior high school women in the australian Capital Territory: prevalence and risk factors for genital Human papillomavirus infection." University of Canberra. Health Sciences, 2004. http://erl.canberra.edu.au./public/adt-AUC20060410.140559.
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An association between persistent Human papillomavirus (HPV) infection in women
and cervical cancer has been established. Young women are particularly at risk of
acquiring sexually transmitted infections such as HPV because of risky sexual activity
and physiological immaturity. While at risk though, young women have been shown
to be amenable to health promoting initiatives. There are a small number of
international studies concerning adolescent HPV infection and the risk factors
associated with infection, but there is currently no evidence on the prevalence and risk
factors for HPV in an Australian, sexually active female adolescent population. This
study aimed to provide evidence of the prevalence of HPV, risk factors associated
with infection and the patterns of sexual activity in a female sexually active, senior
high school population in the Australian Capital Territory.
Participants in this study were a convenience sample of 161 sexually active 16-19
year old females who had an HPV test who were attending a senior high school in the
Australian Capital Territory. Nurses and doctors using a clinical record collected
information about sexual and other risk behaviours. Self-obtained vaginal swabs were
tested for HPV DNA using the polymerase chain reaction method and genotyping was
undertaken.
The HPV prevalence in this cohort of young women was 1 1.2%. High-risk genotypes
were found in 55.5% and multiple genotypes were found in 38.8%. There was a
significant association found between HPV infection and having had more than one
male partner with whom vaginal intercourse had occurred in the previous six months.
No statistically significant association was found between HPV and the age of
coitarche, length of time young women had been sexually active, condom use, and
smoking or alcohol intake. A young age at coitarche was common for this group.
Smoking and alcohol use was seen in large proportions in this group.
This is the first Australian study that has examined the prevalence and risk factors for
genital HPV in this demographic group. The HPV prevalence is lower than in
international studies in comparable groups, in similar age groups and much lower than
in older women both in Australia and overseas. With the comparatively low
prevalence comes an opportunity for important public health interventions for this
group including routine Pap smears, vaccination against the high-risk types of HPV
when this becomes available and strategies for young women to reduce their number
of male sexual partners. A substantial amount of young women in this study were
sexually active aged under 16 years. Whilst this was not identified as being a risk
factor in this study, it is both a health and personal safety issue for these young
women. There is a demonstrated need for health promotion strategies for this cohort
about the consumption of safe levels of alcohol and for smoking cessation. Further
research is recommended that includes a repetition of this study with a larger sample,
the use of a prospective study design to identify trends in infection and examination of
HPV prevalence and risk factors for a variety of populations.
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Konopnicki, Deborah. "Infection with high risk Human Papillomavirus (HRHPV) among HIV-positive women: epidemiology, natural history and impact of combined antiretroviral therapy." Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209264.
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L’infection persistante par les papillomavirus (HPV) dits « à haut risque » induit le cancer du col. Chez les femmes infectées par le VIH, les infections par ces HPV oncogènes et les lésions associées, allant des dysplasies au cancer invasif, sont plus fréquentes, plus sévères et de moins bon pronostic que chez les femmes non porteuses du VIH. Etonnamment, alors qu’il a été clairement établi que l’importance de la pathologie liée à HPV est directement proportionnelle au degré d’immunodépression des patientes porteuses du VIH, il n’a pas pu être démontré qu’un traitement antirétroviral efficace contre le VIH permettant d’améliorer l’immunité, diminue l’infection par ces HPV. Entre janvier 2002 et décembre 2012, nous avons constitué une cohorte prospective de dépistage et de suivi de l’infection cervicale par HPV à haut risque incluant plus de 900 femmes traitées à la consultation du Centre de Référence SIDA de l’hôpital Saint-Pierre. Nos résultats montrent que chez ces femmes pour la plupart d’origine Africaine et traitée avec succès pour le VIH depuis plusieurs années, la prévalence et l’incidence de l’infection par HPV oncogène sont beaucoup plus importantes que dans la population belge générale ou que chez les femmes séropositives vivant dans d’autres pays occidentaux. Grâce à un suivi longitudinal de plusieurs années, nous avons pu démontrer que le risque d’être infectée par un HPV oncogène est significativement réduit sous trithérapie anti-VIH sous réserve d’obtenir une charge virale indétectable à <50 cp/ml pendant plus de 3 ans ou une restauration immunitaire à >500 lymphocytes CD4+/µL pendant plus d’un an et demi. Ces résultats ont été confirmés dans l’analyse que nous avons faite sur les nombreuses dysplasies cervicales également retrouvées dans notre cohorte. Enfin, nous avons trouvé que la distribution des génotypes d’HPV de nos patientes est similaire à celle trouvée en Afrique sub-saharienne impliquant que la couverture offerte par les vaccins anti-HPV varie entre moins de 30% pour les vaccins bi- ou quadrivalent actuellement disponibles à 80% pour le vaccin nanovalent en développement. Notre travail met en lumière l’étendue particulièrement importante de l’infection par HPV à haut risque chez les femmes séropositives vivant en Belgique et offre de nouveaux éléments de réflexion afin d’adapter à leurs particularités les recommandations belges et les critères de remboursement à la fois pour le dépistage du cancer cervical et la vaccination anti-HPV.
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Persistent infection with human papillomavirus (HPV) called “at high risk” induces cervical cancer. In HIV-positive women, infection with these oncogenic HPV and HPV-induced lesions ranging from cervical dysplasia to invasive cancer are more frequent, more severe and have a worst outcome than in HIV-negative women. An intriguing paradox is that, although it has been clearly demonstrated that high risk HPV infection and associated diseases are increased by progressive immune deficiency, the introduction of efficient therapy against HIV leading to improved immunity has not been associated with a decrease in oncogenic HPV infection or HPV-induced lesions.
Between January 2002 and December 2012, we have built a prospective cohort to screen and follow-up cervical infection by high risk HPV in more than 900 women treated for HIV in the AIDS Reference centre of Saint-Pierre Hospital. We have shown that among these women mainly from Sub-Saharan African origin and successfully treated for HIV for several years, the prevalence and incidence rate of high risk HPV are much higher than in the general population from Belgium or in HIV-positive women from other western countries. After several years of longitudinal follow up, we have demonstrated that the risk of infection by oncogenic HPV is significantly reduced by efficient therapy against HIV provided that HIV viral load has been sustainly suppressed below 50 cp/ml for more than 3 years or that immunity has been increased more than 500 CD4+T cells/µl for more than 1.5 years. These results have been confirmed in the analysis on cervical dysplasia which is also very prevalent in our cohort. At last, we have found that the HPV genotype distribution in our population is very similar to the one found in Sub-Saharan Africa. We have estimated that the coverage offered by the vaccines against HPV in our cohort is less than 30% for the currently available bi- or quadrivalent vaccine but reaches 80% with the future nanovalent vaccine. Our results highlight many differences in the HPV infection and associated diseases in HIV-positive women compared to HIV-negative women; these differences should be taken into account to adapt to our specific population the current Belgian guidelines or the reimbursement criteria on cervical screening and on vaccines against HPV.
Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished
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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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Nielson, Carrie. "Human Papillomavirus Prevalence in Asymptomatic Men." Diss., The University of Arizona, 2006. http://hdl.handle.net/10150/194193.
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Introduction: Human papillomavirus (HPV) is the sexually transmitted etiologic agent of cervical cancer. While HPV infects both men and women, little is known about HPV infection in men. Specifically, knowledge of the prevalence of type-specific HPV infection and the distribution of these infections by anogenital anatomic site in men is incomplete. Evaluation of factors associated with HPV infection based on complete anogenital sampling and with HPV-16 antibody detection may lead to a better understanding of HPV transmission and prevention.Methods: A total of 493 asymptomatic men ages 18 to 40 years old were recruited in Tucson, Arizona, and Tampa, Florida, from 2003 to 2006. Eligibility requirements included having had sex with a woman within the past year and having no history of genital warts. Testing for HPV from anogenital swabs from six anatomic sites and semen was conducted by PCR and reverse line blot genotyping for 37 HPV types. Serum antibodies for HPV-16 were detected by ELISA. Self-administered demographic, health, and sexual history/behavior questionnaires were collected. HPV prevalence and type distributions by anatomic site were calculated, as was seroprevalence of HPV-16 antibodies. Multivariate logistic regression was used to identify independent risk factors for HPV infection at any anatomic site and for having HPV-16 antibodies.Results: HPV was detected in at least one sample for 303 (65.4%) men, with 29.2% of men having an oncogenic infection and 36.3% having a non-oncogenic infection. Multiple HPV types were detected in 27.2% of men. Factors associated with infection were a greater lifetime number of female sexual partners, currently smoking 10 or more cigarettes per day, lack of condom use, and more sexual partners in the past three months. HPV-16 antibodies were detected in the serum of 63 (12.8%) men, and detection was associated with increasing age and concurrent detection of HPV DNA in perianal or anal canal samples.Discussion: The combination of more complete anogenital sampling and sensitive HPV detection for 37 HPV types resulted in a higher HPV prevalence in asymptomatic men than previously reported. Smoking and condom use were the most important modifiable risk factors for HPV in men. These results have implications for research of HPV transmission.
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Esber, Allahna Lauren. "HPV risk factors and screening among Malawian women." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1458645591.
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Winer, Rachel L. "Genital HPV infection and E7 mRNA viral load : incidence, risk factors, and relations to genital neoplasias /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/10917.
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Nyitray, Alan Gaspar. "Prevalence of and Risk Factors for Anal Human Papillomavirus in Heterosexual Men." Diss., The University of Arizona, 2008. http://hdl.handle.net/10150/194207.
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Introduction: The incidence of anal cancer, whose primary cause is human papillomavirus (HPV) infection, has increased in United States (US) men almost three-fold in three decades; however, little is known about the epidemiology of anal HPV, especially in heterosexual men. Furthermore, advancements in knowledge about the epidemiology of anal HPV may be hampered by measurement error in the collection of sexual behavior data. Methods: From two US cities, behavioral data and anal biological specimens were collected from 253 men who acknowledged sexual intercourse with a woman in the previous year. PCR and genotyping were used to assess the presence of HPV DNA. In addition, two HPV questionnaires were assessed for test-retest reliability: the first was a self-administered questionnaire associated with the collection of the biological specimens while the second was a computer-assisted self-interview (CASI) with 1069 men in Brazil, Mexico, and the US. Results: Based on DNA analysis, overall anal HPV prevalence was 24.8% in 222 men who acknowledged no prior sexual intercourse with men. Risk factors independently associated with anal HPV were lifetime number of female sexual partners and frequency of sex with females in the past month. Based on kappa and intraclass correlation coefficients (ICC), both HPV questionnaires were found to be highly reliable with low refusal rates; however, three discrete measures in the multi-national interview asking for the number of sexual partners had lower reliability. The ICC of these questions increased to greater than or equal to 0.79 when a small number of extreme outliers (less than or equal to 3) were removed. Predictors of unreliable reporting were age and lifetime number of female sexual partners while years of education was inversely associated with unreliable reporting. Discussion: These results suggest anal HPV is common in heterosexual men. Risk factors associated with anal HPV did not explain how HPV was transmitted to the anal region. Both instruments used to collect sexual behavior data were highly reliable including the CASI instrument used in three culturally and linguistically distinct countries; however, caution is warranted with discrete measures that ask participants to report the number of sexual partners.
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Ross-Innes, Caryn Sarah. "The role of human papillomavirus (HPV) E6 proteins as a risk factor for oesophageal cancer." Master's thesis, University of Cape Town, 2007. http://hdl.handle.net/11427/3148.
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Includes bibliographical references (leaves 74-83).Oesophageal squamous cell carcinoma (OSCC) is a major cancer in South Africa, affecting mainly black males. Several risk factors for OSCC have been reported but this study focuses on the role of human papilloma virus (HPV) in the development of OSCC. HPV is a well-known risk factor for cervical cancer resulting in its classification into low- and high-risk HPV types. The role of the different HPV types in OSCC development is not known, but in cervical cancer the critical HPV transforming gene has been shown to be E6. In this project, the effects of HPV11 E6, a low-risk type, and HPV18 E6, a high-risk type, were investigated by transfecting HPV-negative cell lines (EPC2-hTERT, MCF12A and Rat1) with HPV11 and HPV18 E6.
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Helmy, Hannah Louise. "“This Isn’t Like Diphtheria, You Know?”: The Sociocultural Context of Human Papillomavirus Immunization, Potential Mandates, and Narratives of Risk Among." Scholar Commons, 2008. https://scholarcommons.usf.edu/etd/288.
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Many in the biomedical community have praised the recently released Human Papillomavirus (HPV) vaccine, Gardasil, for having the potential to significantly reduce the disease burden of cervical cancer and genital warts. However, complex intersections of ideology, morality, and politics have made this new vaccine considerably contested, particularly as public debate has turned to the ethics of state-mandated HPV vaccination for 11-12 year old girls. Subsequently, the extent to which mandatory vaccinations are accepted by parents and implications regarding the infringement of these coercive measures on their rights to make health care decisions for their children has become powerfully positioned in public discourse. This research seeks to examine how mothers of girls conceptualize Gardasil and the potential mandates in order to illuminate the multi-faceted socio-cultural context of risk embedded within this immunization. Major themes that emerged from in-depth interviews include diverse perceptions of the risk of HPV for their daughter(s) specifically, children as actual or potential sexual beings, concerns about vaccine safety, mistrust of pharmaceutical companies and government collusion, and conceiving of vaccination against HPV as imbued with a either a moral or cancer prevention subtext. The need for collaboration and communication between the medical and governmental institutions who promote vaccines such as Gardasil and the public who politically and socially consumes them has been apparent throughout my research. Applied anthropologists have a unique role to play by situating diverse stakeholder perspectives across interdisciplinary fields in order to develop more appropriate and informed policies.
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Kumakech, Edward. "Human immunodeficiency virus (HIV), human papillomavirus (HPV) and cervical cancer prevention in Uganda : prevalence, risk factors, benefits and challenges of post-exposure profylaxis, screening integration and vaccination." Doctoral thesis, Örebro universitet, Institutionen för hälsovetenskap och medicin, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-44517.
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Petito, Guilherme. "DETECÇÃO E GENOTIPAGEM DE HPV EM CARCINOMAS DE CAVIDADE ORAL E OROFARINGE." Pontifícia Universidade Católica de Goiás, 2014. http://localhost:8080/tede/handle/tede/2390.
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Previous issue date: 2014-06-25The human papillomavirus (HPV) has been associated with the risk and prognosis of oral cavity and oropharynx carcinomas. This study aimed to estimate the prevalence and genotype distribution of HPV 16 and 18 in oral cavity and oropharyngeal carcinomas, as well as their associations with clinical and histopathological factors of tumors. It is a retrospective descriptive study, with gathered data analysis of 82 medical records and paraffin blocks containing specimens of oral cavity carcinomas and oropharynx diagnosed at the Hospital Araújo Jorge (HAJ), in Goiânia-GO, between 2005 and 2007. The chain reaction polymerase (PCR) was used for HPV detection and genotyping. Among the 82 evaluated patients, 78% were male. The average age of patients was 58 years. Risk factors, like smoking (78 %) and ethylism (70.8 %), were registered in the studied group. HPV DNA was detected in 21 cases (25.6%; 95% CI: 16.9 to 36.6) of which 33.3% were HPV 16 and 14.3% HPV 18. The presence of metastases lymph node and deaths were less common in tumors with HPV, suggesting a better prognosis for these cases, however, the differences between the groups were not statistically significant. The data described in the present study, regarding the presence of the HPV genome, and the high risk oncogenic genotypes, HPV16 and HPV18, in oral cavity and oropharynx carcinomas highlights the importance of vaccination against HPV in such tumours.
O Papilomavírus humano (HPV), tem sido associado com o risco e o prognóstico dos carcinomas da cavidade oral e orofaringe. Este estudo teve como objetivo estimar a prevalência e a distribuição genotípica do HPV 16 e 18 em carcinomas de cavidade oral e orofaringe, bem como suas associações aos fatores clínicos e histopatológicos dos tumores. É um estudo retrospectivo descritivo, com dados coletados análise de 82 prontuários e de blocos de parafina contendo espécimes de carcinomas de cavidade oral e orofaringe diagnosticados no Hospital Araújo Jorge (HAJ), em Goiânia-GO, entre 2005 e 2007. A reação em cadeia da polimerase (PCR) foi usada para detecção e genotipagem do HPV. Dentre os 82 pacientes avaliados, 78% eram do sexo masculino. A média de idade dos pacientes foi de 58 anos. Fatores de risco, como tabagismo (78%) e etilismo (70,8%) foram registrados no grupo estudado. O DNA do HPV foi detectado em 21 casos (25,6%; IC 95%: 16,9 36,6) dos quais 33,3% eram o HPV 16 e 14,3% o HPV 18. A presença de metástases linfonodais e os óbitos foram menos frequentes nos tumores que apresentaram HPV, sugerindo um melhor prognóstico para esses casos, porém, as diferenças entre os grupos não foram estatisticamente significativas. Os dados descritos no presente estudo, com relação à presença do genoma do HPV, incluindo os genótipos de alto risco, HPV16 e HPV18, destacam a importância de vacinação contra o HPV no controle dos carcinomas de cavidade oral e orofaringe.
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Lu, Beibei. "Serum Antibodies to Human Papillomavirus Type 6, 11, 16 and 18 and Their Role in the Natural History of HPV Infection in Men." Scholar Commons, 2010. http://scholarcommons.usf.edu/etd/3486.
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Our understanding of humoral immune response to human papillomavirus (HPV) infection has been mainly derived from studies in women. Very little is known about humoral immune response to HPV in men. There is also a growing interest in understanding the burden of HPV exposure in the subgroups of the male population, including men who have sex with women (MSW), men who have sex with men (MSM) and men who have sex with both men and women (MSMW). This dissertation was undertaken to understand and characterize humoral immune response, measured by detectable serum antibody IgG, to HPV 6, 11, 16 and 18 infection, to estimates seroprevalence of HPV 6, 11, 16 and 18, to determine the associations of sociodemographic and sexual behavioral factors with seroprevalence of individual HPV types, and to evaluate the role of serum antibodies in the subsequent acquisition of infection with the same HPV type, genetically related and un-related HPV types.
Three studies that compose of this dissertation were conducted within the framework of two longitudinal studies of HPV infection in men: a single-site natural history study of male residents of Tucson, Arizona (the 1st study: N=285); and a multinational natural history study of healthy men residing in São Paulo, Brazil, Cuernavaca, Mexico, and Tampa, Florida (the 2nd study: N=1477; the 3rd study: N=2187). Men were recruited using similar eligibility criteria in both natural history studies and followed every 6 months for a maximum of 18 months in the single-site study and 48 months in the multi-national study. HPV DNA status was assessed using the PGMY09/11 L1 consensus primer system and the Linear Array HPV Genotyping Protocol. Testing of serum antibodies to HPV 6, 11, 16 and 18 was performed with virus-like particle-based ELISA assays.
Data from our studies indicate that exposure to HPV 6, 11, 16 and 18, the four HPV types targeted in the currently license HPV vaccines, is common. Of 285 male residents of Tucson, Arizona, 28.8% of them were seropositive to HPV 16 and/or 18 at study entry. Similarly, approximately one third of 1477 participants of the multi-national male HPV natural history study were seropositive to at least one vaccine HPV type, with the percentage of 21.8% in U.S. site, 33.4% in Mexico site, and 49.1% in Brazil site. It is also noted that seroprevalence of individual vaccine HPV types is greatly elevated among men of different sexual practices. Seroprevalence of HPV 6, 11, 16 and/or 18 was twice as high among MSM and MSMW compared to MSW. Likewise, seroprevalence of individual HPV types was two fold or higher among MSW and MSMW.
Our findings suggest that the predominant predictors of seropositivity to HPV 6, 11, 16 and 18 are age and same-sex sexual behaviors. Seroprevalence increased with age among young-to-middle-aged men with significant upward age trends observed for HPV 11, 16 and 18. MSM, compared to MSW, more likely to be seropositive to HPV 16 or 18. Similarly, men who practiced same-sex anal sex, compared to those who did not, were significantly more likely to be seropositive to HPV 6, 11, 16 and 18, respectively.
Among 276 men free of HPV 16 at enrollment in Tucson, We did not detect statistically significant associations between the baseline serum antibodies to HPV 16 and/or 18 and subsequent risk of infection with homogeneous HPV types or related-HPV types. Of 2187 men residing in three countries who tested HPV 16 negative at enrollment, the risk of subsequent HPV 16 infection was not associated with enrollment HPV 16 serum antibodies status.
Our data provide important estimates of population exposure to vaccine HPV types for future studies modeling potential vaccine impact and vaccine cost effectiveness in men. Our findings also support strategic vaccination of males as an effective preventive measure for HPV-related diseases and cancers in men and their sex partners, men and women alike.
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Rosa, Maria Inês da. "O papilomavirus humano e lesões do colo uterino." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2007. http://hdl.handle.net/10183/12119.
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Analisamos uma coorte de mulheres no sul do Brasil, com objetivo de identificar associações epidemiológicas para persistência e cura da infecção pelo HPV e realizamos uma metanálise para determinar a acurácia da telomerase nas lesões precursoras do câncer cervical. Métodos: O estudo de coorte foi iniciado em fevereiro de 2003. Foram coletados espécimes cervicais para citologia oncótica e para detecção do DNA HPV na entrada do estudo e no seguimento. O desfecho foi dividido em quatro categorias: (1) persistência, (2) conversão (3) cura. A quarta categoria (referência) eram mulheres negativas no início que permaneceram negativas. Foram usados o teste χ2 de Pearson, regressão logística multinomial e Kaplan- Meier para análise estatística. Para a metanálise foram incluídos estudos que comparavam o teste de telomerase (TRAP) e anatomopatológicos, obtidos por biópsias cervicais para diagnóstico de lesões cervicais. Resultados: A Incidência de HPV foi 12,3%. O HPV16 foi o tipo mais encontrado (18,6%), entre as 501 mulheres do estudo.Trinta e quatro mulheres (6,78%) ficaram persistentemente infectadas pelo HPV, estando essa categoria associada à idade da sexarca inferior a 21 anos (OR = 3,14, IC 95%, 1,43-6,87) e a quatro ou mais parceiros durante a vida (OR = 2,48 IC 95%, 1,14-5,41). No período mediano de 19 meses, 80,7 % das mulheres tinham curado o HPV, a cura foi significativamente associado à cor preta (OR= 3,44 IC 95%, 1,55-7,65), co-infecção com C. trachomatis no arrolamento (OR= 3,26, IC 95%, 1,85-5,76) e história de já ter realizado exame de Papanicolaou (OR= 3,48, IC 95%, 1,51- 8,00). Na metanálise dez estudos foram analisados, os quais incluíram 1069 mulheres. Para lesões intraepiteliais de baixo grau (LIEBG) vs. normal ou lesões benignas, encontrou-se uma positividade do teste da telomerase, sendo que o resultado da odds ratio para diagnóstico (DOR) foi de (DOR = 3,2, IC 95%,1,9-5,6). Nas lesões intraepiteliais de alto grau (LIEAG) vs LIEBG, normal ou benigna: (DOR = 5,8, IC 95%, 3.1-10). )]. Encontrou-se uma DORelevada de 8,1 (IC 95%: 3,2-20) nas lesões de câncer cervical vs LIEAG. Da mesma forma, nas lesões de câncer cervical vs. LIEBG, a razão de chance foi elevada, com uma DOR de 40,9 (IC 95%: 18,2-91). Conclusões: A persistência da infecção pelo HPV foi associada com a sexarca precoce e ao número de parceiros sexuais na vida, sugerindo que estratégias de orientação sexual podem modificar as taxas de persistência do HPV. A associação da cura do HPV com história prévia de realização de Papanicolaou salienta a importância de aprimorar os programas de rastreamento de câncer cervical. Futuros estudos da associação de infecções ginecológicas com cura da infecção pelo HPV são necessários. Na metanálise nossos dados suportam a corrente hipótese da atividade da telomerase como um evento precoce na carcinogênese e que poderia estar associado ao início e à progressão de lesões cervicais.We analysed a cohort of women in Southern Brazil with the aim to identify epidemiological correlates for persistence and clearance of cervical HPV infection. A quantitative systematic review was performed to estimate the accuracy of telomerase assay in cervical lesions. Methods: A cohort study was started on February 2003. Cervical smears were collected to perform Pap cytology and HPV DNA detection at baseline and during the follow up. The outcome was constructed in four categories (1) persistence of HPV DNA; (2) conversion; (3) clearance of HPV. Pearson’s χ2 test, multinomial logistic regression and univariate analysis using the log-rank test were performed. Meta-analysis studies that evaluated the telomerase test (telomerase repeated amplification protocol) for the diagnosis of cervix lesions and compared it to paraffin-embedded sections as the diagnostic standard were included. Results: Incidence of HPV DNA: 12.3%. HPV16 was the most frequent type (18.6%) among 501 women in the study. Thirty-four women were persistently infected with HPV, which was associated with age below 21 years at first intercourse (OR 3.14, 95% CI, 1.43-6.87) and ≥ 4 sexual partners during lifetime (OR 2.48, 95% CI, 1.14-5.41). In a median period of 19 months, 80.7% of women had clearance of HPV, which was associated with black race (OR 3.44, 95% CI, 1.55-7.65), co-infection with C. trachomatis at baseline (OR 3.26, 95% CI, 1.85-5.76) and history of previous Pap smear (OR 3.48, 95% CI, 1.51-8.00). In meta-analysis ten studies were analyzed, which included 1,069 women. The diagnostic odds ratio (DOR) for a positive telomerase test for Lo-SIL vs. normal or benign lesions was 3.2 (95% CI, 1.9-5.6). The DOR for a positive telomerase test for Hi-SIL vs. Lo-SIL, normal or benign lesions was 5.8 (95% CI, 3.1-10). For cervix cancer vs. Hi-SIL, the DOR for a positive telomerase test was 8.1 (95% CI, 3.2-20.3) and for cervix cancer vs. Lo-SIL, normal or benign lesions, it was 40.9 (95% CI, 18.2-91). Conclusions: Persistence of HPV infection wasassociated with early age at first intercourse and number of sexual partners during lifetime, suggesting that strategies for sexual orientation may modify the rates of HPV persistence. The association of HPV clearance with a history of previous Pap smear screening highlights the importance of improving cervical screening programs. Further studies on the association of gynaecological infections with HPV clearance are needed. In meta-analysis our data support the current hypothesis that telomerase may activate an early event in cervical carcinogenesis, that could be associated with the initiation and progression of cervical lesions.
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Bernardo, Brittany Marie. "The association of socioeconomic status with cervical cancer risk misperceptions, Pap smear screening adherence and cervical outcomes among Ohio Appalachian women." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1585049392819132.
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Gibson, Ryan Taylor. "The Eukaryotic SMC5/6 Complex Represses the Replicative Program of High-Risk Human Papillomavirus." Diss., 2020. http://hdl.handle.net/1805/24609.
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Indiana University-Purdue University Indianapolis (IUPUI)Human papillomaviruses (HPVs) are non-enveloped, circular double-stranded DNA viruses that infect basal keratinocytes of stratified squamous epithelia. High-risk HPV (HR-HPV) infection causes nearly all cervical cancers and an increasing number of head and neck cancers. While prophylactic vaccinations have reduced the incidence of HPV infection and attributable cancers, currently there is no cure for pre-existing HPV infection. As such, HPV remains a global health threat and a better understanding of HPV biology remains of significant medical importance for identification of novel therapeutic targets. The multi-subunit structural maintenance of chromosomes 5/6 complex (SMC5/6) is comprised of SMC5, SMC6 and NSE1-4. SMC5/6 is essential for homologous recombination DNA repair and reportedly functions as an antiviral factor during hepatitis B and herpes simplex-1 viral infections. Intriguingly, SMC5/6 has been found to associate with HR-HPV E2 proteins, which are multifunctional transcription factors essential to regulation of viral replication and transcription. The function of SMC5/6 associations with E2, as well as its role during HR-HPV infection remain unclear and we explored this question in the context of HR-HPV- 31. SMC6 interacted with HPV-31 E2 and co-immunoprecipitation of SMC6/E2 complexes required the E2 transactivation domain, inferring SMC6 association is limited to the full-length E2 isoform. Depletion of SMC6 and NSE3 increased HPV replication and transcription in keratinocytes stably maintaining episomal HPV-31, suggesting that the SMC5/6 complex represses these processes. Neither SMC6 nor NSE3 co-IP the viral E1 DNA helicase alone or E1/E2 complexes but the association of SMC6 with E2 was reduced in the presence of E1, indicating that SMC6 competes with E1 for E2 binding. This infers that SMC6 repression of the viral replicative program may involve inhibiting initiation of viral replication by disrupting E2 interactions with E1. Chromatin immunoprecipitation determined that SMC6 is present on episomal HPV-31 genomes, alluding to a possible role for SMC5/6 in modifying the chromatin state of viral DNA. Taken together, these findings describe a novel function for SMC5/6 as a repressor of the HPV-31 replicative program.
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Huang, Po-Che, and 黃柏哲. "Identifying MicroRNA Biomarkers for Human Papillomavirus-infected Cervical Cancer Based on High-risk HPV Subtypes." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/6h5ufh.
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碩士元智大學
資訊工程學系
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Cervical cancer is the fourth most common cancer in women. More than 90 % cervical cancer cases are caused by human papilloma virus (HPV). There are several studies about identifying biomarkers of HPV-infected cervical cancer. However, those studies only focused on HPV16 or HPV18 infected cervical cancer, but in fact all of high-risk HPV are potential to lead cervical cancer. Therefore, we aim to discover the divergence between all high-risk HPV types infected cervical cancer to understand the biological mechanism by microRNA and gene expression data. We collected microRNA and gene expression data of HPV-infected cervical cancer from TCGA. According to HPV type of samples, we cluster into several subtypes and totally obtained six HPV subtypes including 16, 18, 45, 31, 33 and 39. Based on tumor samples of six HPV subtypes, we identified type-specific microRNAs of each HPV subtype. We also applied hierarchical method and principal components analysis to cluster HPV-infected cervical cancer samples by type-specific microRNAs. In addition, we performed machine learning approach such as correlation based feature selection and support vector machine (SVM) method to classify HPV-infected cervical cancer samples by type-specific microRNAs. Importantly, we have clinical NGS data to validate our type-specific microRNAs. Consequently, functional enrichment analysis (FEA) of type-specific microRNA-mediated genes will be performed to understand the biological mechanism of cervical cancer infected by different HPV subtypes. From functional enrichment analysis of type-specific microRNA-mediated genes, we discovered that there are some microRNA involve in biological process or pathway about HPV infection and cervical cancer. Importantly, some of them are also validated in our clinical NGS data. Based on those microRNAs, we construct the type-specific microRNA-mediated regulatory network of HPV 16, 18 and 33 to suggest a possible and significant role in HPV infection and cervical cancer. Especially in HPV18-specific microRNA-mediated regulatory network, hsa-mir-15b has been discovered that it will be induced with E2F-controlled genes which involved in differentiation, development, cell proliferation and apoptosis due to HPV infection.
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Nicolo', Sabrina. "Interplay among microbial communities, epithelial cells, and immune system in vaginal mucosa of women with high-risk Human Papillomavirus infection." Doctoral thesis, 2022. http://hdl.handle.net/2158/1275958.
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Persistent infection with HR-HPVs is a primary cause of cervical cancer worldwide. Among HR-HPV, subtypes HPV-16 and HPV-18 are most associated with invasive cancers and are thought to cause approximately 65-75% of cases. Emerging evidence indicates that CVM plays a substantial role in the viral persistence and subsequent disease. Accordingly, a role of CVM composition in the regression of high grade of CIN lesions has been reported. Data from clinical studies show that Lactobacillus-dominated cervicovaginal microbiota and L. crispatus particularly was positively associated with the clearance of the virus and negatively associated with the neoplastic progression of intraepithelial lesions. In contrast, vaginal-dysbiosis associated bacteria were correlated with the persistence of HR-HPVs infection and with increasing cancer risk. The molecular mechanisms based on such effects are not elucidated yet.
Aim of this study was to investigate whether each vaginal bacterial species, commonly found in cervicovaginal microbial communities, may affect the expression of viral oncogenes and accelerate the neoplastic transformation of HR-HPV transformed cells. For this purpose, the HPV-16 transformed SiHa epithelial cells (with ~1,2 copies of integrated viral genome) were selected as experimental model of CIN-1 and bacterial strains, representatives of the 5 CSTs, were evaluated for their effect on the expression of viral oncogenic proteins E6 and E7, the fate of cellular oncosuppressor protein p53, the effects on cell survival/growth of HPV-transformed SiHa cells, and the synthesis of matrix-degrading enzymes.
Our data show that G. vaginalis and M. micronuciformis directly induce the expression of the viral E6 and E7 oncogenes and the synthesis of the respective products by SiHa cells. These bacteria also induce the expression of E6-AP, a ubiquitin protein ligase that binds to E6 and induce p53 degradation. As consequence of E6 activation and p53 degradation, cell proliferation is increased. L. crispatus never induces the expression of viral oncogenes or proteins, while L. iners and L. jensenii slightly induce the viral E7 gene
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expression but not E6. In contrast to G. vaginalis or M. micronuciformis, vaginal Lactobacilli did not affect the cell cycle of cervical epithelial cells.
G. vaginalis and M. micronuciformis also induce high expression of MMP-9, a cellular protein which overexpression has been observed in different malignant tumors.
All these data were obtained by using live bacterial cells, supernatants, or bacterial lysates. Supernatants from bacterial culture are not effective in the system suggesting the responsivity of very labile or not secreted products. Although not all strains of G. vaginalis have the same property to induce the expression of viral oncogenes and oncoproteins, our data strongly suggest that this species together with M. micronuciformis may play an important role in neoplastic transformation of HR-HPV infected cell.
According with data from clinical data, the presence of G. vaginalis or M. micronuciformis in the vaginal fluid of women with persistent HR-HPV infection or CIN-1 should direct these groups to a close follow-up or to surgical excision respectively.
Abbreviations: HR-HPV (High-Risk Human Papillomavirus), CVM (cervicovaginal microbiota), CST (community state type), CIN (cervical intraepithelial neoplasia), CIN-1 (low grade of cervical intraepithelial neoplasia), E6-AP (E6-Associated Protein), L. (Lactobacillus), G. (Gardnerella), M. (Megasphaera), MMP-9 (Matrix Metalloproteinase-9).
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Barrow, Lisa C. "E7 PROTEINS OF HIGH-RISK (TYPE 16) AND LOW-RISK (TYPE 6) HUMAN PAPILLOMAVIRUSES REGULATE p130 DIFFERENTLY." Thesis, 2010. http://hdl.handle.net/1805/2277.
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Indiana University-Purdue University Indianapolis (IUPUI)Human papillomaviruses (HPVs) are one of the most common causes of sexually transmitted disease in the world. HPVs are divided into high-risk (HR) or low-risk (LR) types based on their oncogenic potential. HPVs 16 and 18 are considered HR types and can cause cervical cancer. HPVs 6 and 11 are classified as LR and are associated with condyloma acuminata (genital warts). Viral proteins of both HR and LR HPVs must be able to facilitate a replication competent environment. The E7 proteins of LR and HR HPVs are responsible for maintenance of S-phase activity in infected cells. HR E7 proteins target all pRb family members (pRb, p107 and p130) for degradation. LR E7 does not target pRb or p107 for degradation, but does target p130 for degradation. Immunohistochemistry experiments on HPV 6 infected patient biopsies of condyloma acuminata showed that detection of p130 was decreased in the presence of the whole HPV 6 genome. Further, the effect of HR HPV 16 E7 and LR HPV 6 E7 on p130 intracellular localization and half-life was examined. Experiments were performed using human foreskin keratinocytes transduced with HPV 6 E7, HPV 16 E7 or parental vector. Nuclear/cytoplasmic fractionation and immunofluorescence showed that, in contrast to control and HPV 6 E7-expressing cells, a greater amount of p130 was present in the cytoplasm in the viii presence of HPV 16 E7. The half-life of p130, relative to control cells, was decreased in the cytoplasm in the presence of HPV 6 E7 or HPV 16 E7, but only decreased by HPV 6 E7 in the nucleus. Inhibition of proteasomal degradation extended the half-life of p130, regardless of intracellular localization. Experiments were also conducted to detect E7-binding partners. Cyclin C and cullin 5 were identified as proteins capable of binding to both HPV 6 E7 and HPV 16 E7. Preliminary experiments showed that decreasing protein levels of p600, a binding partner of both HPV 6 E7 and HPV 16 E7, by RNA interference might affect p130 stability. Elucidating the mechanisms of p130 degradation may identify potential targets for preventing degradation of p130 and allowing restoration of cell cycle control.
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CHEUNG, MELANIE T. "The Risk of Serious Respiratory-Related Events Following Immunization with the Quadrivalent Human Papillomavirus (qHPV) Vaccine: The Ontario Grade 8 HPV Vaccine Cohort Study." Thesis, 2014. http://hdl.handle.net/1974/12040.
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Background: The qHPV vaccine has the potential to significantly reduce the burden of HPV-related diseases, including cervical cancer. However, a recent systematic review of clinical trials has suggested that the risk of bronchospasm may be increased by this vaccine, and a large observational study has reported an increased risk of anaphylaxis.
Objectives: To determine whether qHPV vaccination increases the risk of incident asthma, asthma exacerbation, and anaphylaxis.
Methods: A population-based retrospective cohort of grade 8 girls eligible for Ontario’s HPV immunization program between 2007 and 2011 was identified using the province’s administrative health and immunization databases. Cohort members were followed from September 1st of their grade 8 year until their date of death or end of study (March 31st, 2012). The self-controlled case series method, a self-matched, case-based analysis was used to assess the effect of qHPV vaccination on the risk of SRREs, and rate ratios (RRs) and 95% confidence intervals for each outcome was estimated using conditional Poisson regression.
Results: The cohort consisted of 125,575 girls with a mean age of 13.2 years, 57.7% of whom received at least one dose of the qHPV vaccine. During an average of 2.5 years of follow-up, 1473 cases of incident asthma, 901 of asthma exacerbation and 38 of anaphylaxis were identified. HPV vaccination was not associated with an increased risk of incident asthma or asthma exacerbation (RRadj 0.76, 95% CI 0.37-1.54 and RRadj 0.74, 95% CI 0.27-2.00, respectively), and these associations were unchanged by the presence of risk factors and time since vaccination. There was also no evidence of an increased risk of anaphylaxis following qHPV vaccination as demonstrated by an absence of cases of anaphylaxis occurring on the day of vaccination.
Conclusions: This large, population-based study provides strong evidence that the qHPV vaccine does not increase the risk of developing or exacerbating asthma, and additional evidence for the lack of an increased risk of anaphylaxis in the younger populations targeted by HPV immunization programs. These findings add to the growing body of evidence on the safety of the qHPV vaccine.Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2014-04-16 19:20:41.019
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FANG, TIAN. "THE RISK OF MISCARRIAGE FOLLOWING IMMUNIZATION OF THE BIVALENT HUMAN PAPILLOMAVIRUS (HPV) - 16/18 VACCINE: A BAYESIAN APPROACH." Thesis, 2013. http://hdl.handle.net/1974/7790.
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Background: Cervarix is a prophylactic vaccine used in preventing cervical cancer associated with human papillomavirus types 16/18. A previous study that investigated the risk of miscarriage associated with this bivalent vaccine by pooled analysis of data from two clinical trials, showed a numerically higher but statistically insignificant miscarriage rate in the HPV arm for pregnancies that began within three months following the vaccination. We explored this issue using an alternative statistical approach.
Objectives: To develop a hierarchical Bayes model to identify the potential time-dependent risk window of miscarriage rate associated with the bivalent HPV vaccine.
Methods: This study comprised the development of a hierarchical Bayes Model with its model inference and the application of this model to a real-world question. A multivariate logistic model was proposed that involved an indicator variable to accommodate a risk window with lower and higher cut-off points. Gibbs Sampling algorithms were used for the inference on the parameters of interest. Over ninety sets of simulation studies were conducted to evaluate the performance of the proposed method and estimate the power in detecting the risk effect. The Bayesian approach was then compared to the existing traditional approaches (e.g. the permutation test). The proposed model was applied to the subpopulation of pregnant women from the Costa Rica Vaccine Trial.
Results: In simulation studies, the Bayesian model demonstrated a better performance over the traditional approaches. It showed higher power than the traditional hypothesis testing in detecting the risk effect; it was more informative than the permutation test because it provided both the point estimates and the corresponding credible intervals for the cut-points and the ratio of odds ratios. In the analysis of the CVT data, we observed an effect of 1.13 (95% credible interval: 0.49 to 2.75), implying no significant evidence to support the hypothesis that HPV is associated with a higher miscarriage rate.
Conclusions: The hierarchical Bayes model can be applied to investigate the time-dependent risk of adverse events in clinical trials. Using the new Bayesian method, no significant risk of miscarriage in the Costa Rica Vaccine Trial was established, which is consistent with previous report.Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2013-01-30 23:20:39.859
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SMITH, MICHAELA ANNE. "Occurrence, determinants and dynamics of HPV coinfections in a cohort of Montreal university students." Thesis, 2011. http://hdl.handle.net/1974/6383.
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Background: Coinfections with multiple types of human papillomavirus (HPV) are a common occurrence among HPV-infected individuals, but the clinical significance and etiology of these infections remain unclear. Though current evidence suggests that women with coinfections have increased HPV exposure (i.e. more sexual partners), it is also hypothesized that these women may represent a subgroup with increased HPV susceptibility, though this has been rarely studied to date.
Purpose: The purpose of this project was to examine the occurrence, determinants and dynamics of HPV coinfections in a cohort of university students in order to explore the relationship(s) between coinfections, lifestyle factors and immunological susceptibility.
Methods: This project is based on a secondary analysis of data from the McGill-Concordia Cohort, a longitudinal study of the natural history of HPV infection in 621 female university students in Montreal, Quebec. Participants were followed for 2 years at 6-month intervals. At each visit, cervical specimens were collected for cytology and HPV testing, and women completed a questionnaire about lifestyle and risk behaviours. Two definitions of coinfections were used: cumulative coinfection over follow-up and concurrent coinfection at each visit. Kaplan-Meier techniques were used to estimate incidence and duration of coinfections and multiple logistic regression was used to identify determinants of coinfections and associations between coinfections and squamous intraepithelial lesions (SIL).
Results: More than half of the cohort became infected with HPV and of those, over 60% acquired multiple HPV types over follow-up. Incidence of coinfections was significantly increased among HPV-infected women at enrollment. The most important determinant of coinfection occurrence was number of sexual partners (both lifetime and new), though some genes of the immune response (HLA-DQB1*06:02, HLA-G*01:01:03 and HLA-G*01:01:05) were also significant predictors. Women with coinfections, particularly those with 4+ HPV types, also had longer infection durations and greatly increased odds of SIL.
Conclusions: Women with coinfections acquire new HPV types at an increased rate and have greater HPV persistence and occurrence of SIL, which may indicate immunological susceptibility. HPV coinfections mainly occur due to increased sexual activity but a decreased immune response to the virus may also be involved in a subset of women.Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2011-04-21 01:04:26.265
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Liu, Yiran. "ASSESSING THE RISK FOR AUTOIMMUNE DISORDERS FOLLOWING USE OF THE QUADRIVALENT HUMAN PAPILLOMAVIRUS VACCINE: THE ONTARIO GRADE 8 HPV VACCINE COHORT STUDY." Thesis, 2014. http://hdl.handle.net/1974/12071.
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Introduction: In 2007 Ontario implemented a grade 8 quadrivalent human papillomavirus (qHPV) vaccination program targeting the virus that causes cervical cancer. Despite being 6 years post-implementation, few post-licensure studies have assessed the safety of the qHPV vaccine in this adolescent population. Since autoimmune disorders are often targeted for post-marketing surveillance by regulatory agencies, it is important to assess the risk of developing an autoimmune disorder post-qHPV vaccination.
Objectives: The objectives of this thesis were to assess the risk for developing an autoimmune disorder following qHPV vaccination, assess for effect modification by the presence of predisposing risk factors, identify the period of highest risk and explore the risk for individual autoimmune disorders.
Methods: A population-based retrospective cohort of girls eligible for Ontario’s qHPV vaccination program was identified using population-based databases. The risk of autoimmune disorders following qHPV vaccination was ascertained using the self-controlled case series method.
Results: The risk of developing a new autoimmune disorder, adjusted for age, seasonality, concurrent vaccines and infections was 1.28 (95% CI: 0.87 – 1.89), and this association was independent of a history of immune-mediated disorders (p=0.39). The risk was not increased during days 7-24 post-vaccination (adjusted RR = 0.87, 95% CI: 0.43 – 1.74), but appeared to increase thereafter (adjusted RR = 1.36, 95% CI: 0.77 – 2.41 and RR = 1.62, 95% CI 0.94 – 2.78 respectively, for days 25 – 42 and days 43 – 60), although these differences were non-significant. The risk may be increased for certain disorders including Bell’s palsy (RR = 2.30, 95% CI: 0.67 – 7.95), systemic autoimmune rheumatic disorders (RR = 1.84, 95% CI: 0.42 – 8.02), Hashimoto’s disease (RR = 1.39, 95% CI: 0.46 – 4.22), and juvenile rheumatoid arthritis (RR = 1.31, 95% CI: 0.83 – 2.08), although none of these associations were statistically significant.
Conclusion: This thesis demonstrated that no statistically significant increased risk for autoimmune disorders following qHPV vaccination was detected. However, there remains some uncertainty about the safety of the qHPV vaccine for a subset of the autoimmune disorders. The results from this analysis need to be pooled with those of other studies to confirm whether these are true safety signals.Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2014-04-23 22:30:41.428