Made available in DSpace on 2016-08-10T10:39:25Z (GMT). No. of bitstreams: 1 LARISSA FERNANDES DE CARVALHO.pdf: 2794684 bytes, checksum: a117224e860c989d8636ee7805cfc679 (MD5) Previous issue date: 2010-05-31 / Cancer has been a major public health problem both in developed and developing countries . Each year, cancer is responsible for more than six million deaths, imposing a population burden that claims about 12% of all causes of that worldwide. Under a genetic perspective, there are two major classes of gene that hold an important role on cancer development: the proto-oncogenes and the tumor suppress genes. Mutations in these genes are the underlying cause of uncontrolled cell proliferation. Under the spectrum of male urological tumors, penile carcinoma is the one that most resembles cervical carcinoma in women. Epidemiological studies have frequently implicated HPV genome as a potential initiator factor for carcinomas of different anatomical sites. HPV role in cancer induction is well documented for cervical carcinomas and a significant association has been found in up to 99,7% of all cases worldwide. The occurrence of HPV in both male and female genital areas has increased the scientific interest around the potential association of HPV genome and penile carcinomas. The HPV genome is mode of one copy of the double-stranded circular DNA molecule, organized in three distinct regions: a Long Control Region (LCR), an Early (E) and a Late (L) protein coding regions. Following viral insertion in a cell genome, the viral LCR becomes the target of an intracellular regulatory mechanism. When infected cells lose this control mechanism, tumor progression towards malignancy and increased viral gene expression occur. Penile cancer is a rare disease, however by far the most common type is the squamous cell carcinoma which is found in about 95% of the penile malignancies. As any other Sexually Transmitted Disease, men are the major link in the chain of infection of HPV. The Polimerase Chain Reactions is the most sensitive procedure to detect and genotype HPV DNA in human biological samples. The current study is a meta-analysis which comprised the result of several studies that using PCR detected and genotyped HPV genome in association with penile cancers. Herein we report on the results of 39 research articles published from 1989 to 2009. We found the published data had large heterogeneity, tending to significance when combined within the 95% confidence interval. The DermonSaimonian-Laird analysis indicated significance between HPV infection and penile cancer development. / O HPV atua como uma importante causa de câncer cervical, em cerca de 99,7% dos casos em todo mundo. Como ocorre em toda infecção de transmissão sexual, o homem é o principal elo na cadeia epidemiológica do HPV e tem sido bastante discutido a associação deste vírus aos carcinomas penianos. O câncer de pênis é uma doença rara, sendo o carcinoma de células escamosas responsável por 95% dos casos. Assim, a infecção por HPV em homens, promove modificações bioquímicas e moleculares, alterando significativamente a população de células, através da interação do genoma viral com o genoma da célula hospedeira ou de proteínas virais com proteínas celulares necessárias ao controle do ciclo celular, como as proteínas supressoras de tumor pRb e p53, podendo desencadear a progressão para o processo maligno. Dentre as técnicas moleculares para detecção de DNA do HPV, a PCR é a mais sensível, pois é capaz de identificar o tipo do HPV. Neste contexto, o presente estudo teve como objetivo, investigar a associação entre o HPV e os pacientes com câncer de pênis através de uma meta-análise. Um procedimento destinado a examinar, de modo simultâneo, os resultados de várias investigações sobre um mesmo tópico, de forma a gerar conclusões com maior segurança e confiabilidade. De um total de quarenta e quatro (44) artigos encontrados, foram incluídos na meta-análise, trinta e nove (39) artigos e duas (2) dissertações entre os anos de 1989 a 2009 que estabeleciam a co-relação e utilizavam as mesmas técnicas e primers para detecção e genotipagem do HPV. Na presente meta-análise, observou-se que os artigos analisados apresentaram heterogeneidade quando avaliados os tipos de HPV 16 e 18, em conjunto. O HPV do tipo 18 isolado não apresentou significância, enquanto o HPV 16 demonstrou estar significativamente relacionado ao carcinoma espinocelular de pênis. Pelo teste de DerSimonian-Laird os resultados dos estudos combinados demonstram que os mesmos são significativos e heterogêneos em relação a IC 95%. Assim, pode-se concluir que a associação entre câncer de pênis e HPV se confirma por meta-análise, demonstrando assim a importância da força estatística da meta-análise diante dos estudos isolados na tentativa de desenvolvimento de novas estratégias de prevenção do HPV.

Made available in DSpace on 2016-08-10T10:54:58Z (GMT). No. of bitstreams: 1 LUANA CARVALHO DA SILVA.pdf: 1919863 bytes, checksum: 43845eab7ebc38ce4258c581e7475ae9 (MD5) Previous issue date: 2015-05-29 / Cervical cancer is considered an important public health problem, since it affects and kills a large number of women throughout the world. The main risk factor for cervical cancer is the infection by the Human Papillomavirus (HPV), considered to be the most common sexually transmitted disease, in the present days. Despite the high incidence, cervical cancer prevention programs have been implemented worldwide, through the Pap smear and HPV vaccine. Objective: To evaluate the perception and knowledge of nursing students about HPV infection, HPV associated diseases and HPV vaccine, in a private education institution, in Goiânia-GO. METHODS: It comprises a descriptive study with a quantitative approach, carried out through a questionnaire with objective questions that allowed to quantify the knowledge of the participants with regard to HPV infection, diseases associated with the virus and HPV vaccine, ensuring the analysis and interpretation of the results. The research was applied to 361 scholars from both genders. RESULTS: Correct answers related to the knowledge about HPV infection ranged from 40.3% to 99.2%, with an average of 73.8%; about the diseases associated with viruses, the indexes of correct answers ranged from 24.8% to 82.8%, with an average of 61.8%; regarding the HPV vaccine, the indexes of correct answers ranged from 40.8% to 93.0%, averaging 74.6%. CONCLUSION: The results allowed to conclude that academic nursing knowledge was reasonable in relation to HPV infection and HPV vaccine. However, insufficient results were obtained with respect to the knowledge about cancer of the uterine cervix. Thus, we highlight the need for continuing education about the subject, during and after graduation of these professionals, since nursing presents an important role in health teams and in the process of health education of the population. / O câncer do colo do útero é considerado um importante problema de saúde pública, pois ainda acomete e mata um grande número de mulheres em todo mundo. O principal fator de risco para o câncer do colo do útero é a infecção pelo Papilomavírus humano (HPV), considerada a doença sexualmente transmissível mais comum, nos dias atuais. Apesar da alta incidência, o câncer do colo do útero apresenta programa de prevenção, por meio do exame de Papanicolaou e da vacina anti-HPV. OBJETIVO: Avaliar a percepção e o conhecimento dos acadêmicos de enfermagem de uma instituição de ensino superior privada de Goiânia-GO, sobre a infecção pelo HPV, o câncer do colo do útero e a vacina anti-HPV. MÉTODOS: Estudo descritivo com abordagem quantitativa, realizado por meio de questionário com perguntas objetivas que permitiu quantificar o conhecimento dos participantes com relação à infecção pelo HPV, as doenças associadas ao vírus e a vacina anti-HPV, garantindo a análise e interpretação dos resultados. A pesquisa foi aplicada a 361 acadêmicos de ambos os gêneros. RESULTADOS: Os níveis de acertos observados para as questões relacionadas ao conhecimento sobre a infecção pelo HPV variaram de 40,3% a 99,2%, com média de 73,8%; sobre o câncer do colo do útero, os índices de acertos variaram de 24,8% a 82,8%, com média de 61,8%; com relação à vacina anti-HPV, os índices de acertos variaram de 40,8% a 93,0%, com média de 74,6%. CONLUSÃO: Os resultados desse estudo permitiram concluir que o conhecimento dos acadêmicos de enfermagem foi razoável em relação à infecção pelo HPV e à vacina anti-HPV. Entretanto, resultados insuficientes foram obtidos com relação ao conhecimento sobre o câncer do colo do útero. Assim, destacase a necessidade da educação continuada durante e após a graduação desses profissionais, pois a enfermagem apresenta um importante papel em equipes de saúde e no processo de educação em saúde da população.

Seres humanos dependem incessantemente de um sistema de reconhecimento efetivo contra infecções para sobreviver. Dentre as diversas proteínas que compõem a resposta imune inata estão os receptores do tipo Toll (TLR Toll-like Receptors), que possuem a função de reconhecer padrões moleculares associados a patógenos e dar início a uma resposta imune adequada. O carcinoma do colo uterino é uma das principais causas de morte de mulheres por câncer mundialmente, sendo o terceiro tipo de câncer mais comum entre mulheres. Este tipo de neoplasia é vinculada etiologicamente à infecção pelo Papilomavírus humano (HPV). Dentre as principais proteínas virais, E6 e E7 são responsáveis pela manipulação dos processos celulares para promover ciclo viral, sendo essenciais no processo de transformação celular. Nesse contexto, o objetivo deste trabalho foi investigar a importância da via de sinalização de TLRs sobre a infecção por HPV. O polimorfismo rs5743836, na região promotora de TLR9, capaz de alterar a expressão deste receptor, foi estudado quanto à influência sobre a história natural da infecção por HPV em uma coorte de mulheres brasileiras; nenhuma associação relevante foi encontrada, indicando que este polimorfismo não interfere significativamente na resposta à infecção e risco de desenvolvimento de lesões no colo do útero causadas por HPV. Proteínas componentes da via de TLRs demonstraram serem alvos de interação com E6 de HPV16; dentre elas, o notável adaptador MyD88 e IKKε, enzima ativadora de importantes transfatores do sistema imune. Estas interações foram aqui estudadas. A interação de E6 com MyD88 resultou em estabilização da proteína viral, o que parece não depender do sítio LxxLL presente em MyD88, como ocorre com outros parceiros moleculares de E6. O sítio de interação de E6 com IKKε coincide com a região onde se localiza o sítio catalítico desta enzima, sugerindo a ação de E6 na ativação de proteínas alvo de IKKε. Esta interação foi observada em queratinócitos, células alvo das infecções por HPV. A produção de citocinas foi afetada por E6 de HPV16, resultando num aumento da quantidade de IL-8 e IL-6; a indução desta citocina poderia ser explicada pela ativação de IKKε. Estes resultados apontam para a capacidade do HPV16 de interferir com o sistema imune, contribuindo para o processo de carcinogênese. / Humans constantly rely on an effective recognition system against infections in order to survive. Among various proteins that compose the innate immune response, Toll-like Receptors (TLRs) have the role to recognize pathogen associated molecular patterns and initiate a proper immune response. The cervical cancer is one of the main causes of women death worldwide, being the third most common cancer type among women. This type of neoplasia is etiologically associated with the Human papillomavirus (HPV) infection. E6 and E7, two main viral proteins, are responsible for manipulating the cellular processes to promote the virus\' life-cycle, being essential to the cellular transformation process. In the context, the objective of this work was to investigate the relevance of the TLR signaling pathway on the HPV infection. The rs5743836 polymorphism, in the TLR9 promoter region, capable of altering this receptor\'s expression, was studied regarding its influence on the natural history of HPV infection in a Brazilian women cohort; no relevant association was found, indicating that this polymorphism does not interfere significantly in the infection response and risk of developing cervix lesions caused by HPV. Component proteins of TLR pathway were shown to be interaction targets of HPV16 E6; among them, the notable adaptor MyD88 and IKKε, enzyme that activates important immune system transfactors. These interactions were studied in this work. The interaction of E6 with MyD88 resulted in the stabilization of the viral protein, which seems independent of the LxxLL site present on MyD88, as in other E6 molecular partners. The interaction site on IKK with E6 matches with the region containing the enzyme\'s catalytic site, suggesting an influence of E6 in the activation of IKKε target proteins. This interaction was observed in keratinocytes, natural targets of HPV infections. The cytokines production was altered by HPV16 E6, resulting in an increase of IL-8 and IL-6 concentration; the induction of the latter could be explained by the activation of IKKε. These results point to the ability of HPV16 of interfering with the immune system, contributing to the carcinogenesis process.

Les infections à Papillomavirus Humain (HPV) sont des infections sexuellement transmissibles très fréquentes. La persistance de ces infections est un facteur causal du cancer du col de l’utérus et est aussi à l’origine d’autres cancers de la zone ano-génitale et de verrues génitales chez les femmes et chez les hommes. Depuis l’introduction de deux vaccins bivalent et quadrivalent permettant de prévenir certains types d’HPV, de nombreux modèles mathématiques ont été développés afin d’estimer l’impact potentiel de différentes stratégies de vaccination. L’objectif de ce travail de thèse a été d’estimer l’impact potentiel de la vaccination en France sur l’incidence de certains cancers liés à l’HPV, notamment le cancer du col de l’utérus et le cancer anal chez les femmes françaises ; ainsi que sur la prévalence des infections à HPV 6/11/16/18. Différents modèles dynamiques de type déterministe ont été développés. Ils sont représentés par des systèmes d’équations différentielles ordinaires. Une étude théorique du comportement asymptotique d’un premier modèle comportant peu de strates a été réalisée. Le nombre de reproduction de base R0 et le nombre de reproduction avec vaccination Rv ont été estimés. Des modèles plus complexes ont intégré une structure d’âge et de comportement sexuel. Les modélisations réalisées permettent de conclure à l’impact important de la vaccination sur la prévalence des infections à HPV et sur l’incidence des cancers du col de l’utérus et de la zone anale chez les femmes françaises dans un délai de quelques décennies, si l’on prend en compte les taux de vaccination observés en France au début de la campagne de vaccination / Human Papillomavirus infection (HPV) is the most frequent sexually transmitted disease. Epidemiological studies have established a causal relationship between HPV infections and occurence of cervical cancer. These infections have also been incriminated in anogenital cancers and anogenital warts among women and men. Since the introduction of bivalent and quadrivalent vaccines which offer protection against some HPV genotypes, many mathematical models have been developed in order to assess the potential impact of vaccine strategies. The aim of this thesis work was to assess the potential impact of HPV vaccination in France on the incidence of some cancers linked with HPV, particularly cervical cancer and anal cancer in French women, and on the prevalence of HPV 6/11/16/18 infections. Different deterministic dynamic models have been developped. They are represented by systems of ordinary differential equations. A theoretical analysis of the asymptotic behavior for a first model with few strata is realized. The basic reproduction number R0 and the vaccinated reproduction number Rv are assessed. More complex models taking into account age and sexual behavior have been developed. Using vaccination rates observed in France at the launch of the vaccination campaign, our modeling shows the large impact of vaccination on HPV prevalences, on cervical cancer and anal cancer incidences among French women within a few decades

Made available in DSpace on 2015-04-11T13:38:22Z (GMT). No. of bitstreams: 1 francisca.pdf: 878093 bytes, checksum: 251097fdfe9003556935b61ec3a58ab8 (MD5) Previous issue date: 2012-06-27 / The human papillomavirus (HPV) is recognized as a major risk factor related to cervical cancer. The identification of HPV types of high risk can aid in the prevention of malignant lesions of the cervix. This study aims to determine and genotype HPV in women with a cytological result of ASC-US and LSIL. This is a cross-sectional study with an analytical component in women attended the Fundação Alfredo da Matta - FUAM. The patients were selected from the file examination of the Laboratory of Cytology of FUAM from January 2009 to July 2011 and requested to attend the DST clinic through active search in order to make a new collection of material for revaluation cytological, molecular detection and genotyping of HPV. Molecular detection was performed by Nested-PCR targeting the L1 region of the viral capsid. PCR products were analyzed on an agarose gel. Out of 100 patients selected, 70% (70/100) participated in the study, 34 of them had the cytological result of ASC-US and LSIL of 36. After reevaluation cytological 8 (11.4%) patients had cytology within normal limits, 33 (47.2%) inflammatory cytology, 22 (31.4%) ASC-US, 6 (8.6%) LSIL, 1 (1.4%) HSIL. HPV was identified in 28.6% (20/70) of the samples. Of the 20 patients HPV DNA-positive 1 had cytology within normal limits, 6 inflammatory cytology, 10 ASC-US and 2 LSIL and 1 HSIL. After the genotyping were identified the following HPV types 6, 16, 58, 61, 70, 83, 84 and 85. The most prevalent HPV 25% was HPV 58. The presence of HPV high-risk oncogenic stresses the importance of actions aimed at preventing the transmission of this virus and tracking of diseases in the city of Manaus. / O Papillomavírus humano (HPV) é reconhecido como o principal fator de risco relacionado do câncer cervical. A identificação de tipos de HPV de alto risco pode auxiliar na prevenção de lesões malignas do colo do útero. Este estudo tem como objetivo determinar e genotipar o HPV em mulheres com resultado citológico de Lesão Intraepitelial de Baixo grau (LSIL) e Células Escamosas Atípicas Significado Indeterminado (ASC-US). Trata-se de um estudo de corte transversal com componente analítico em mulheres atendidas na Fundação Alfredo da Matta - FUAM. As pacientes foram selecionadas a partir do arquivo de exames do Laboratório de Citologia da FUAM no período de janeiro de 2009 a julho de 2011 e solicitadas a comparecer ao ambulatório de DST por meio de busca ativa, a fim de fazer uma nova coleta de material para reavaliação citológica, detecção molecular e genotipagem do HPV. A detecção molecular foi realizada pela técnica de Nested-PCR tendo como alvo a região L1 do capsídeo viral. Os produtos da PCR foram analisados em gel de agarose. Do total de 100 pacientes selecionadas, 70% (70/100) participaram do estudo, sendo que 34 delas tinham resultado citológico de ASC-US e 36 de LSIL. Após reavaliação citológica 8(11,4%) pacientes apresentaram citologia dentro dos limites da normalidade, 33(47,2%) citologia inflamatória, 22(31,4) ASC-US, 6(8,6%) LSIL, 1(1,4%) HSIL. O HPV foi identificado em 28,6% (20/70) das amostras examinadas. Das 20 pacientes HPV-DNA positivas 1 caso apresentou citologia dentro do limite da normalidade, 6 citologia inflamatória, 10 ASC-US, 2 LSIL e 1 caso apresentou HSIL. Após a genotipagem foram identificados os seguintes tipos de HPV: 6, 16, 58, 61, 70, 83, 84 e 85. O HPV mais prevalente com 5 casos em 20 positivos foi o HPV 58. A presença do HPV de alto risco oncogênico destaca a importância de ações voltadas para a prevenção na transmissão desse vírus e no rastreamento das doenças relacionadas, na cidade de Manaus.

Submitted by admin tede (tede@pucgoias.edu.br) on 2017-10-02T12:52:56Z No. of bitstreams: 1 JOSÉ ANTONIO VIANA DE MORAIS 3.pdf: 4387158 bytes, checksum: 813e3206f05ae2289634baf546698b46 (MD5) / Made available in DSpace on 2017-10-02T12:52:57Z (GMT). No. of bitstreams: 1 JOSÉ ANTONIO VIANA DE MORAIS 3.pdf: 4387158 bytes, checksum: 813e3206f05ae2289634baf546698b46 (MD5) Previous issue date: 2010-05-26 / Human papillomavirus (HPV) is one of the infections through sexual intercourse more often disseminated throughout the world. In Brazil it is estimated that there are around 3 to 6 million cases of HPV. There are few studies about HPV in men. This study examined the therapeutic response of patients men infected with HPV and treated topic with a solution of 90% trichloroacetic acid (ATA 90%). Were treated between January 2007 and December 2008, at the Hospital for Tropical Diseases in Araguaina (TO) 1056 patients undergoing clinical analysis by means of physical examination and penioscopia. The records of these patients were analyzed and found that 589 (55.8%) were diagnosed with HPV. Of these, 529 were selected for study as these met the following inclusion criteria: patients with macroscopic and penioscópico of HPV, which did not undergo any treatment before consultation, which were treated only with ATA 90% before and monitored for any recurrence, at least twelve months. After collecting data it was found that only 68 (12,8%) patients treated with ATA 90% had recurrence of lesions. The age of initial and final of HPV ranged from 18 to 73 years. The average age of patients with recurrence was 34.9 years, coinciding with the peak of sexual activity and the presence of multiple parters. About 80% of cases of recurrence occurred in the first six months. The association with other sexual diseases was recorded and the most prevalent pathologies: balanoposthistis (31,3%), genital herpes (9,2%), gonococal urethritis (2,8%) and no-gonococcal urethritis (0,9%). We found that the presence of other STDs contributes to treatment failure, whereas 75% of cases had tumor recurrence ATA 90% occurred in patients with an STD associated with HPV. Regarding the location of the lesions, it was found that 61.1% occurred at the distal end of the male phallus. The number of lesions detected per patient ranged from 1 to 9, with the majority (82.3%) patients had 2-5 lesions. In this study, we identified that the prevalence of HPV infection in men, STD clinic with urological monitoring was high. The therapeutic efficacy of ATA 90% was higher than the values commonly found in the literature and the recurrence rate of patients was low. We suggest that monitoring of patients with HPV after treatment with ATA is 90% done with routine queries for up to twenty-four months and quarterly consultations with the cases of recurrence. We emphasize the need for a focus on serving the man aiming to prevent controllable diseases evolve into malignancies. / O papilomavírus humano (HPV) é uma das infecções por via sexual mais frequentemente disseminadas em todo o mundo. No Brasil estima-se que existam em torno de 3 a 6 milhões de casos de HPV. Há poucos estudos sobre o HPV em homens. Este trabalho analisou a resposta terapêutica de pacientes do sexo masculino infectados HPV e tratados topicamente com solução de ácido tricloroacético à 90% (ATA 90%). Foram atendidos entre janeiro de 2007 e dezembro de 2008, no ambulatório do Hospital de Doenças Tropicais de Araguaína (TO), 1056 pacientes submetidos a analise clínica por meio do exame físico minucioso e penioscopia. Os prontuários desses pacientes foram analisados e verificou-se que 589 (55,8%) apresentaram diagnóstico de HPV. Destes, 529 foram selecionados para o estudo por atenderem aos seguintes critérios de inclusão: pacientes com diagnóstico macroscópico e penioscópico de HPV, que não realizaram qualquer tratamento antes da consulta, que foram tratados exclusivamente com ATA 90% antes de qualquer recidiva e monitorados por, no mínimo, doze meses. Após coleta de dados verificou-se que apenas 68 (12,8%) pacientes que realizaram tratamento com ATA 90% apresentaram recidiva das lesões. A faixa etária de acometimento do HPV variou de 18 a 73 anos. A idade média dos pacientes com recidiva foi de 34,9 anos, coincidente com o pico de atividade sexual e a presença de múltiplos parceiros. Cerca de 80% dos casos de recidiva ocorreram nos seis primeiros meses. A associação com outras DSTs foi observada, sendo as patologias mais prevalentes: a balanopostite (31,3%), o herpes genital (9,2%), a uretrite gonocócica (2,8%) e a uretrite não gonocócica (0,9%). Verificamos que a presença de outra DST contribui para o insucesso terapêutico, visto que 75% dos casos de recidiva pós ATA 90% ocorreram em pacientes portadores de alguma DST associada ao HPV. Em relação à localização das lesões, verificou-se que 61,1% ocorreram na extremidade distal do falo masculino. O número de lesões encontradas por paciente variou de 1 a 9, sendo que a maioria (82,3%) dos pacientes apresentou de 2 a 5 lesões. Neste estudo, identificamos que a prevalência da infecção por HPV em homens, em ambulatório de DST com acompanhamento urológico foi elevada. A eficácia terapêutica do ATA 90% mostrou-se maior que os valores comumente encontrados na literatura e o índice de recidiva dos pacientes foi baixo. Sugerimos que o acompanhamento dos pacientes com HPV após o tratamento com ATA 90% seja realizado com consultas rotineiras por até vinte e quatro meses e com consultas trimestrais para os casos de recidiva. Reforçamos a necessidade de um enfoque no atendimento do homem com intuito de evitar que doenças controláveis evoluam para doenças oncológicas.

Background: Persistent infection with high risk HPV is a necessary but insufficient cause of cervical cancer. Behavioural, viral and host factors modulate the risk of HPV persistence. In this thesis, I explore the role of the vaginal microbiota, a host factor and the presence of multiple HPV infections, a viral factor in HPV persistence. Considering the limited data on the epidemiology of HPV related diseases in low and middle-countries (LMIC), and the limited success of cervical cancer screening strategies in many LMIC, I provide data on the distribution of HPV related diseases in Nigeria and evaluate the acceptability of innovative strategies to increase cervical cancer screening uptake. Methods/Results: To achieve my aims, I implemented a longitudinal cohort study of 1,020 women in Nigeria. I begin my results chapters with two methodological papers. Attrition is an important consideration for every longitudinal cohort, particularly in LMIC, therefore, I present my findings on attrition, determinants of attrition and practical strategies to ensure low attrition in studies conducted in LMIC. Considering that sexual behaviour is an important potential confounder in all HPV studies, and the reliability of self-reported history is often questioned, I present findings on the test-retest reliability of self-reported sexual behaviour history collected in my study. Having found that attrition levels were low and that self-reported sexual behaviour history was generally reliable within my cohort, I present my findings on the association between the vaginal microbiota and persistent hrHPV; and the role of multiple HPV infections in viral persistence. I found that the vaginal microbiota was associated with persistent hrHPV in HIV negative women, but not in HIV positive women; and that multiple HPV infections did not increase the risk of viral persistence when compared to single HPV infections. Next, I present my findings on the prevalence and incidence of anogenital warts in Nigeria, with additional reports on the prevalence of cervical cancer and other HPV associated cancers using data from two population based cancer registries. Finally, I present my findings on the acceptability of innovative strategies to improve cervical cancer screening uptake in Nigeria. I found that Nigerian women had a favorable attitude to the use of HPV DNA based screening as part of routine antenatal care, however attitudes towards the use of self-sampling techniques for HPV based cervical cancer screening varied by religious affiliations. Conclusion: In my thesis, I was able to systematically investigate the epidemiology of HPV infections in a LMIC. I considered the distribution of HPV related diseases, host and viral determinants of HPV persistence and investigated control strategies to reduce the burden of cervical cancer in a LMIC. My results provide useful data for surveillance, monitoring and evaluation of control programs on HPV and cervical cancer in Nigeria and may be useful to cervical cancer control programs in other LMIC.

abstract: Biomarkers find a wide variety of applications in oncology from risk assessment to diagnosis and predicting and monitoring recurrence and response to therapy. Developing clinically useful biomarkers for cancer is faced with several challenges, including cancer heterogeneity and factors related to assay development and biomarker performance. Circulating biomarkers offer a rapid, cost-effective, and minimally-invasive window to disease and are ideal for population-based screening. Circulating immune biomarkers are stable, measurable, and can betray the underlying antigen when present below detection levels or even no longer present. This dissertation aims to investigate potential circulating immune biomarkers with applications in cancer detection and novel therapies. Over 600,000 cancers each year are attributed to the human papillomavirus (HPV), including cervical, anogenital and oropharyngeal cancers. A key challenge in understanding HPV immunobiology and developing immune biomarkers is the diversity of HPV types and the need for multiplexed display of HPV antigens. In Project 1, nucleic acid programmable protein arrays displaying the proteomes of 12 HPV types were developed and used for serum immunoprofiling of women with cervical lesions or invasive cervical cancer. These arrays provide a valuable high-throughput tool for measuring the breadth, specificity, heterogeneity, and cross-reactivity of the serologic response to HPV. Project 2 investigates potential biomarkers of immunity to the bacterial CRISPR/Cas9 system that is currently in clinical trials for cancer. Pre-existing B cell and T cell immune responses to Cas9 were detected in humans and Cas9 was modified to eliminate immunodominant epitopes while preserving its function and specificity. This dissertation broadens our understanding of the immunobiology of cervical cancer and provides insights into the immune profiles that could serve as biomarkers of various applications in cancer. / Dissertation/Thesis / Doctoral Dissertation Molecular and Cellular Biology 2018

The human papilloma virus (HPV) is the most frequent cause of sexually transmitted diseases (STDs) and cancers for U.S. adults. The Affordable Care Act (ACA), enacted in 2010, eliminated copay expenses for childhood immunizations and expanded access to health care. The purpose of this secondary data analysis study was to determine if there was an association between ACA and the usage of HPV vaccine among adolescent females in Georgia. Data concerning HPV vaccinations from 2011 to 2015 were obtained from the National Immunization Survey-Teen dataset. Andersen's BM of health care use was applied to ascertain the factors that enhanced the usage of HPV vaccine. Multiple logistic regression analysis was used to determine if there was any association between ACA and HPV vaccination. The study results showed a significant association between ACA and provider visit (p<.05). Also, provider visit was significantly associated with HPV vaccination rate (p<.05). Adolescent females with health insurance had a higher rate of provider visit after the passage of ACA. From 2011 to 2015, 87.2% of insured adolescent females visited their provider. The rate of HPV vaccination increased among the insured adolescent females who visited the provider from 35.3% in 2011 to 53.9% in 2015. Provider visit was identified as the most influencing factor that enhanced usage of HPV vaccine. The knowledge gained from the results contributed to social change by providing insight on how, through increased provider visits, ACA has improved the HPV vaccination rate among teenage females in Georgia. The conclusion will assist in developing effective strategies and policies that will achieve the Healthy People 2020 goal of 80% of herd immunity against HPV.

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.