Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Submitted by Rodolfo Miglioli Badial null (julio.badial@terra.com.br) on 2017-03-24T21:47:33Z No. of bitstreams: 1 Dissertação de Mestrado - FINAL.pdf: 1167468 bytes, checksum: 3b67d890022ead79068bd864c511c2aa (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2017-03-29T13:24:14Z (GMT) No. of bitstreams: 1 badial_rm_me_sjrp.pdf: 1167468 bytes, checksum: 3b67d890022ead79068bd864c511c2aa (MD5) / Made available in DSpace on 2017-03-29T13:24:15Z (GMT). No. of bitstreams: 1 badial_rm_me_sjrp.pdf: 1167468 bytes, checksum: 3b67d890022ead79068bd864c511c2aa (MD5) Previous issue date: 2017-03-07 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Os papilomavírus são vírus de DNA circular fita dupla com diâmetro de aproximadamente 55 nm e forma icosaédrica. São não envelopados e podem induzir tumores epiteliais escamosos em diferentes localizações anatômicas. Eles pertencem à família Papillomaviridae e possuem um genoma de cerca de oito mil pares de bases, protegidos por proteínas do capsídeo. Mais de 200 tipos diferentes de papilomavírus humano (HPV) foram identificados e classificados em dois grupos distintos, alto risco e baixo risco, dependendo de sua associação com o desenvolvimento de câncer. A integração genômica do HPV é um mecanismo de infecção viral persistente, que eventualmente se desenvolve na fase de cancerização. Trata-se de um processo tipicamente aleatório, e pode ocorrer em qualquer local no DNA da célula hospedeira. Em alguns casos, a integração pode contribuir para o desenvolvimento do carcinoma cervical, que é precedido por lesões precursoras como neoplasia intraepitelial cervical ou lesões intraepiteliais escamosas. As infecções crônicas pelo HPV podem ser facilitadas pela coinfecção com o HIV, o que reduz a probabilidade de eliminação espontânea do HPV. Com base nisso, foi investigada a presença do HPV, bem como o seu genótipo em 80 amostras, coletadas em dois anos diferentes, de 40 pacientes coinfectadas com HIV. Como resultado, foi observada a presença do HPV em 59 amostras (73,75%) na qual, os tipos de alto risco foram predominantemente detectados (59,3%). Os tipos mais frequentes foram HPV56 (17%) seguido pelo HPV16 (15,3%). Os resultados foram correlacionados com os fatores de risco associados a coinfecção HPV/HIV apresentados pelas pacientes. Nesta análise, a carga viral do HIV foi associada à ocorrência de lesões cervicais (p=0,045). Desta forma, pode-se concluir que a maior frequência do HPV56 e HPV16 evidencia a importância de incluir o tipo 56 nas vacinas HPV uma vez que o monitoramento das pacientes infectadas pelo HPV56 poderia contribuir para um melhor prognóstico para a infecção pelo HPV. A associação entre a carga viral do HIV e as lesões confirma a importância de monitorizar as doentes coinfectadas com HIV/HPV com carga viral elevada de HIV.

Human Papilloma Virus (HPV) is a conserved DNA virus, which infects mucosal and cutaneous epithelia. Although over 200 types of HPV have been identified which can infect humans, only around 15 high-risk (HR) types have been shown to be responsible for the development of cancer. HPV-16 is the most abundant HR-HPV type being responsible for almost 70% of cervical cancers. HPV-16 consists of 8 genes, the early genes (E1, E2, E4, E5 and the potential oncogenes E6 and E7) responsible for the infection, amplification and proliferation and the late genes (L1 and L2) responsible for the packaging and assembly of the virus. Autophagy, a physiological mechanism of intracellular digestion and recycling of unwanted cellular materials such as aggregated proteins and organelles has been shown to act as a first line defence against invading pathogens. An essential condition for this process is the formation of double membrane structures called the autophagosomes, which can engulf the pathogen or pathogenic proteins and digest them by fusing with endocytic vesicles (lysosomes). Beclin 1 and LC3 are vital proteins involved in the complicated process of the autophagosome formation while SQSTM1/p62 has a key role in the identification and transit of cargo into the forming autophagosomes. This novel work focuses on investigating the role of autophagy in HR-HPV related tumour development and progression in cervical epithelial cells both in vitro and ex vivo.

The Human Papillomavirus (HPV) is a common sexually transmitted infection (STI) and etiological agent of cervical cancer. It has been suggested that religiosity may promote a generalized disassociation between all STIs/STDs, including HPV, and personal relevance thus contributing to lower levels of HPV awareness and knowledge among certain groups. This study sought to identify the role of religiosity as a predictor of HPV awareness and knowledge among women in a Christian university. Religiosity was defined and measured using the Duke University Religion Index (DUREL). The schemata and social identity theories provided the theoretical framework for this study. A total of 173 women completed the modified survey instrument to assess level of HPV awareness and knowledge, attitudes toward premarital sex, and level of religiosity. Multiple linear regression analysis was used to test the hypotheses. Religiosity, as defined by the intrinsic religiosity subscale of the DUREL significantly contributed to HPV awareness (p = .002) and HPV knowledge (p = .036). The positive social change implications of this study include a better understanding of the role of religiosity in HPV awareness and knowledge; consideration of religiosity in dissemination of health information by informing public health policies and programs to ensure adequate and culturally relevant education and awareness about HPV transmission, HPV-related cancers, and HPV vaccination.

Cervical cancer is the second most common malignancy worldwide. Infection with HPV is a necessary cause of cervical. Hispanic women in the U.S. experience significantly higher rates of invasive disease than non-Hispanic Whites. In this population, HPV vaccines hold significant potential to eliminate further disparities in cervical cancer morbidity and mortality. The purpose of this study was to examine factors associated with Human Papillomavirus (HPV) vaccine acceptability among a national sample of Spanish speaking callers to the National Cancer Institute's (NCI) Cancer Information Service (CIS). Specifically this research aimed to identify the sociodemographic, sociocultural and attitudinal determinants of HPV vaccine acceptability. This research involved a cross-sectional study with phone-based interviews conducted in Spanish (n = 836). All female Spanish callers to the CIS were asked to respond to a three-part questionnaire that included items relating to ethnic identity and acculturation, knowledge of cervical cancer and related risk factors, and HPV vaccine acceptability. Descriptive, univariate and multivariate logistic regression were used to characterize the study population and to determine the effect of each of the demographic/sociocultural variables on vaccine acceptance. Independent predictors of HPV vaccine acceptability were determined using multivariate linear regression models. Results showed that HPV vaccine acceptance was high among this group of Hispanic women (78%) and that attitudes about vaccines in general and the HPV vaccine specifically were positive. Factors associated with vaccine acceptance included physician recommendation, awareness and accurate knowledge about HPV, and speaking only or mostly Spanish. Other important predictors included influence of peers, positive attitudes about vaccines in general, higher education and being a mother of a female adolescent. The primary reason cited by those who did not favor vaccination was concern over vaccine safety. This research was the first study looking at vaccine acceptability in a large, national sample of Hispanic women. HPV vaccination can lead to important public health benefits for Hispanic women. Targeted educational interventions must take into account the important sociocultural and attitudinal influences on the decision to vaccinate, such as those identified in the present study. Future educational efforts must involve the physician and take into the account the cultural context of attitudes and beliefs regarding vaccine safety and disease susceptibility. Further studies elucidating the interplay between culture specific beliefs and practices regarding vaccination and the decision to participate in HPV vaccination are needed.

The thesis uses mathematical modeling and analysis to provide insights into the transmission dynamics of Human papillomavirus (HPV), and associated cancers and warts, in a community. A new deterministic model is designed and used to assess the community-wide impact of mass vaccination of new sexually-active susceptible females with the anti-HPV Gardasil vaccine. Conditions for the existence and asymptotic stability of the associated equilibria are derived. Numerical simulations show that the use of Gardasil vaccine could lead to the effective control of the spread of HPV in the community if the vaccine coverage is at least 78%. The model is extended to include the dynamics of the low- and high-risk HPV types and the combined use of the Gardasil and Cervarix anti-HPV vaccines. Overall, this study shows that the prospect of the effective community-wide control of HPV using the currently-available anti-HPV vaccines are encouraging.

Background: Vaccines have been hypothesized in the etiology of autoimmune diseases including type 1 diabetes. There are cases of diabetes reported in the Vaccine Adverse Event Reporting System (VAERS) following the administration of the human papillomavirus (HPV) vaccine, however this potential association has yet to be investigated. The objective of this thesis was to determine whether there is an association between immunization against HPV and the development of type 1 diabetes mellitus in grade 8 girls eligible for Ontario’s vaccination program. Methods: A retrospective, population-based, cohort study of girls residing within an Ontario health unit and eligible for the province’s publicly funded school-based HPV vaccination program between 2007 and 2010 was executed using provincial administrative health databases and the Immunization Recording Information System (IRIS) database. To control for known, unknown and unmeasured time-independent confounders, a self-controlled case series analysis was conducted. The relative incidence and 95% confidence interval were estimated using conditional Poisson regression. Results: The study cohort was comprised of 3465 girls with a mean age of 13.2 years at cohort entry (range 12.7 to 13.6 years). The mean duration of follow up was 2.7 years and ranged from 1.6 to 3.6 years. The proportion of girls who received at least one dose of the qHPV vaccine during the observation period was 58.3% (n=2020). During the study follow-up 15 cases of new onset type 1 diabetes were observed, six of which were classified as etiologically exposed to the qHPV vaccine. Using an indefinite risk window, immunization with the qHPV vaccine was not associated with an increased risk of developing type 1 diabetes (age and season-adjusted RI 0.15; 95% CI 0.02-1.32). Conclusions: The results of this thesis regarding the risk of type 1 diabetes following immunization with the qHPV vaccine are inconclusive as a consequence of the small number of cases identified. However, the random distribution of cases across time and across exposure status suggests that there is no association. Before a definitive conclusion is reached the analysis must be re-conducted on a larger cohort. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2012-05-28 10:39:00.73

The thesis uses mathematical modeling and analysis to provide insights into the transmission dynamics of Human papillomavirus (HPV), and associated cancers and warts, in a community. A new deterministic model is designed and used to assess the community-wide impact of mass vaccination of new sexually-active susceptible females with the anti-HPV Gardasil vaccine. Conditions for the existence and asymptotic stability of the associated equilibria are derived. Numerical simulations show that the use of Gardasil vaccine could lead to the effective control of the spread of HPV in the community if the vaccine coverage is at least 78%. The model is extended to include the dynamics of the low- and high-risk HPV types and the combined use of the Gardasil and Cervarix anti-HPV vaccines. Overall, this study shows that the prospect of the effective community-wide control of HPV using the currently-available anti-HPV vaccines are encouraging.

Background Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States, and adolescents have the highest incidence. To decrease the burden of HPV and HPV-associated cancers, two vaccines were developed and require a 3 dose series. This study assesses factors that may predict whether a teen will either initiate or complete the vaccine series. Methods National Immunization Survey -Teen 2011 data was used to assess demographic (age, sex, and race/ethnicity) and socioeconomic (poverty and insurance status) factors as they related to vaccine initiation and completion. Bivariate and multivariate analyses were used to determine strength of association. Results Females were more likely than males to initiate and complete the series. Compared to whites, Hispanic teens were 1.5 times more likely to initiate but less likely to complete. Blacks were least likely to complete. Teens below the poverty line were more likely to initiate compared to teens above poverty but less likely to complete. Teens with at least one form of health insurance were 1.2 times more likely to complete than those with no insurance. Conclusion HPV vaccination rates are increasing and need to continue to do so. Emphasis needs to be placed on completing the series to confer complete resistance. This is especially true for blacks and Hispanics who are at a higher risk of HPV-related morbidities.

Human papillomavirus (HPV), a major sexually-transmitted disease, causes cervical cancer, in addition to numerous other cancers in females and males. This thesis uses mathematical modeling, theory and simulations to study the transmission dynamics of HPV, and associated dysplasia, in a community. A new deterministic model is designed and used to assess the population-level impact of Pap cytology screening on the transmission dynamics of the disease in a community. The model is rigorously analyzed for its dynamical features, vis-a-vis determining the conditions for the effective control (or elimination) and persistence of the disease. Furthermore, the effect of uncertainties in the estimates of the parameter values used in the numerical simulations of the model is accounted for via uncertainty and sensitivity analysis. Simulations of the model show that Pap screening dramatically reduces the incidence of cervical cancer in the community.