Made available in DSpace on 2014-06-12T18:30:34Z (GMT). No. of bitstreams: 2 arquivo8079_1.pdf: 3985272 bytes, checksum: 76ad6418bcaaac8df5cb2e25da052640 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2004 / Apesar da possibilidade do diagnóstico das lesões precursoras neoplasias intraepiteliais cervicais (NIC) o câncer cervical invasivo ainda representa problema de saúde pública. Na última década, a maior descoberta sobre a etiologia da carcinogênese humana foi o reconhecimento de que o carcinoma cervical é uma rara conseqüência da infecção persistente por tipos oncogênicos de Papilomavirus humano (HPV). O desconhecimento da magnitude da associação entre HPV e NIC, numa região com elevada incidência da expressão clínica da infecção, motivou esta pesquisa. Com o objetivo principal de identificar os fatores de risco para NIC, realizou-se estudo tipo caso-controle, no qual foram incluídas 132 portadoras de NIC (casos) e 96 pacientes com colo normal (controles), atendidas no Setor de Colposcopia do Hospital das Clínicas da Universidade Federal de Pernambuco, no período de novembro de 2001 a agosto de 2002. O estudo teve aprovação do Comitê de Ética em Pesquisa da Instituição onde foi realizado. Os possíveis fatores de risco para NIC foram investigados por meio de formulário padronizado, aplicado a todas as pacientes, para pesquisa de idade, estado civil, grau de instrução, idade ao primeiro coito, número de gestações, número de parceiros sexuais, método contraceptivo utilizado, referência de DST anterior, soropositividade para HIV e tabagismo. Seguiram-se coletas de material para colpocitologia oncótica e para pesquisa de HPV por PCR-RFLP com primers consensus MY09/MY11, exame colposcópico e biópsia com exame histopatológico, nos casos indicados. Para análise estatística de associação de NIC com os fatores de risco, utilizaram-se o Odds Ratio com intervalo de confiança e os testes qui quadrado e Fisher, ao nível de significância de 0,05. Para ajuste do efeito de cada uma das variáveis pelas demais, empregou-se a regressão logística pelo modelo backwards, testado com significância expressa pelo valor de p com grau de máxima verossimilhança. Para análise de concordância, aplicou-se o teste Kappa. No modelo final de regressão múltipla, permaneceram as seguintes variáveis: a infecção por HPV de alto risco oncogênico (OR=12,32 IC95% 3,79-40,08), referência de DST anterior (OR=8,23 IC95% 2,82-24,04), idade ao primeiro coito (OR=4,00 IC95% 1,70-9,39) e tabagismo (OR=3,94 IC95% 1,73-8,98). A soropositividade para HIV comportou-se como fator de proteção para NIC (OR=0,04 IC95% 0,01-0,13). Dentre as 78 amostras com positividade para HPV por PCR-RFLP, houve predomínio de HPV16 ou variante 16 (46,9% do grupo caso), com maior freqüência nas pacientes portadoras de lesões de alto grau. A análise dos aspectos morfológicos no diagnóstico da infecção cervical por HPV demonstrou que a colposcopia apresentou boa concordância com o exame histopatológico, em presença de positividade de DNA-HPV. Dentre os achados colposcópicos mais relevantes para o diagnóstico de lesões cervicais de alto grau e positividade de HPV, destacaram-se o epitélio acetobranco acentuado e mosaico áspero. Considerando os fatores de risco identificados no presente trabalho, concluiu-se que deve haver programas de rastreamento dos grupos com maior probabilidade de desenvolver NIC, por colpocitologia, colposcopia e histopatologia, associadas, quando possível, à biologia molecular, prevenindo o surgimento do câncer invasor

Submitted by Israel Vieira Neto (israel.vieiraneto@ufpe.br) on 2015-03-05T18:26:12Z No. of bitstreams: 2 Mayara Final 07-03.pdf: 795060 bytes, checksum: bb4981feb2c411db622b68087df9e1bc (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) / Made available in DSpace on 2015-03-05T18:26:12Z (GMT). No. of bitstreams: 2 Mayara Final 07-03.pdf: 795060 bytes, checksum: bb4981feb2c411db622b68087df9e1bc (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Previous issue date: 2012 / O Papillomavirus humano (HPV) é responsável por afetar anualmente 500 mil mulheres com câncer cervical invasivo. Fatores de risco podem facilitar a persistência do vírus da cérvice uterina. Polimorfismos genéticos em regiões regulatórias e codificadoras de genes de citocinas estão associadas a patogênese de um vasto número de doenças humanas. Este trabalho objetivou determinar se existe relação entre os polimorfismos existentes na região - G308A do gene TNFα e nas regiões -G137C e -C607A do gene IL18 na susceptibilidade a infecção pelo HPV e na progressão das lesões intraepitelial cervical. O estudo foi realizado com 122 mulheres HPV+ e 132 mulheres HPV- (controle). Os polimorfismos dos genes TNFα e IL18 foram analisados pela técnica Specific Sequence Polymosphism (PCR-SSP) e analisadas em gel de agarose a 1,5%. As análises estatísticas para verificar a significância do estudo dos genótipos foram realizadas utilizando o programa BioEstat 5.0. Os resultados mostraram uma prevalência de 49,18% da infecção pelo HPV-16 e 70,49% delas apresentaram lesão cervical de alto grau. Em relação aos polimorfismos houve associação do alelo mutante na região -308A do gene TNFα e -607A do gene IL18 com a susceptibilidade a infecção pelo HPV (p=0,0008; p<0,0001, respectivamente), mas não foi verificada relação destes genes com a susceptibilidade ao desenvolvimento das lesões (p>0,05). Porém não foi encontrada associação significativa em relação a região na região -137 do gene IL-18. Estes resultados sugerem dois possíveis marcadores genéticos de susceptibilidade a infecção pelo HPV na população em estudo e que estes não podem ser usados como marcadores de progressão da lesão cervical.

Cervical cancer is the second most common cancer in women worldwide. The principal cause of cervical cancer is infection with human papillomavirus (HPV). HPV-16 is a high-risk virus and it is responsible for a high portion of all HPV-caused cancers. The HPV-16 genome consists of early and late genes. The virus initially infects basal cells of the cervix epithelium and in these cells early genes are expressed, whilst late genes, L1 and L2, are only expressed in the upper cell layers of the epithelium. Proteins encoded by the late genes are highly immunogenic, thus it is speculated that expression of the late genes earlier in the virus life cycle could lead to clearance of the virus due to interference of the immune system.     The aim of this study was to treat reporter cell lines with three different small molecule drugs to see if they had the ability to induce HPV-16 late gene expression. The reporter cell lines used in this study had been previously created by transfecting HeLa-cells with plasmids representing the HPV-16 genome. In these plasmids, L1 is replaced with a CAT reporter gene that encodes the CAT protein, which can be easily quantified using a sandwich ELISA.     Upon treating the reporter cell lines with TPA, a significant induction of late gene expression was detected. Furthermore, treatment with valproic acid showed some induction of late gene expression. In conclusion, TPA and valproic acid was deemed to have potential to act as a candidate drugs for treatment of HPV infections.

Polycyclic aromatic hydrocarbons (PAH) have been linked to cancer in humans. Subsequently, 16 of them were listed as priority pollutants by the Environmental Protection Agency in the Clean Water Act. The Florida manatee (Trichechus manatus latirostris) is an herbivorous endangered species that could have the potential to accumulate these compounds. The waters they inhabit have been shown to have PAH concentrations in the sediment from 0.035 μg/g w.w. (wet weight) to 0.686 μg/g w.w. PAH bioaccumulate due to their lipophilic nature and the manatee has a thick blubber layer that may allow for the accumulation of these compounds. Forty-eight archived subcutaneous manatee blubber samples were collected from Florida Fish and Wildlife Conservation Commission Marine Mammal Pathobiology lab and analyzed for 16 known priority pollutant PAH. Samples were then compared to a standard using HPLC analysis. Concentrations were found to range from 0.001 μg/g w.w. to 84.84 μg/g w.w. All 16 priority pollutant PAH were found, however not all 16 were found in any one animal. Forty-six of forty-eight manatee samples analyzed were found to have at least one form of PAH. The number of occurrences of each PAH out of 48 samples ranged from 1-19. The highest average PAH concentration was acenaphthylene with 12.60 μg/g w.w. There was no significant difference (p-value >0.10) between total, carcinogenic and noncarcinogenic PAH, with levels of 2.01 μg/g w.w., 2.18 μg/g w.w. and 1.84 μg/g w.w. respectively. No significant difference (p-value >0.10) was found between year or location of carcass recovery as well as sex of manatee. Averages ranged between 0.02 μg/g w.w. and 18.92 μg/g w.w. for year and 0.15 μg/g w.w. and 5.68 μg/g w.w. for location. Male average levels were 5.21 μg/g w.w., while female averages and perinatal averages were 1.51 μg/g w.w. and 1.147 μg/g w.w. respectively.

Oral human papillomavirus (HPV) infection and its association with head and neck cancers (HNCs) have been established by many studies. The characteristics of HPV-associated HNCs are distinguishable from those of non HPV-associated HNCs. HPV-associated HNCs are related to sexual behaviour, particularly the lifetime number of oral sex partners. The oral and oropharyngeal HPV epidemiology in South African men has not yet been researched. The objective of this study was to determine the oral and oropharyngeal HPV strain prevalence and associated factors in a selected male population in Pretoria, South Africa. Male factory workers were recruited on a voluntary basis to be part of this study. Oral rinse and gargle samples were tested for 37 HPV types using the HPV linear array genotyping kit (Roche Molecular System). A questionnaire was utilised to obtain information regarding age, medical conditions, substance and alcohol use and sexual behaviour. HIV testing was optional. The HPV prevalence was 5.6% among the men (n=125) aged 17-64 years. High risk HPV (hrHPV) types 16 and 68 were found in two men. Amongst the majority of the participants oral sex seemed to be an uncommon practice however, those participants with hrHPV did practice oral sex. A statistically significant association between HPV infection and an increased number of sexual partners (p=0.027) was seen but not between substance use, HIVstatus or clinical mucosal pathology. Considering the oral and oropharyngeal HPV prevalence found in this study compared to those reported in other countries. It is therefore proposed that a larger nationwide study be conducted to give a more representative view of the burden of oral and oropharyngeal HPV infection in South Africa. / Dissertation (MSc)--University of Pretoria, 2014. / lk2014 / Community Dentistry / MSc / Unrestricted

Human papillomaviruses (HPV) are double-stranded, DNA, epitheliotropic viruses that infect skin and mucosal membranes. Over 200 types of HPV have been identified and classified into alpha (α), beta (β), gamma (γ), mu (µ), and nu (ν) genera. HPV in the genus α mainly infect mucosal membranes, cause the majority of the ano-genital cancers, and are widely studied. However, epidemiology of HPV in the other genera, which mainly infect skin, is poorly understood. Few studies have reported the seroprevalence of cutaneous HPV among healthy individuals, and to date, no study has prospectively examined the association between cutaneous HPV seropositivity and development of external genital lesions (EGLs) in men. The objectives of this study were to estimate the seroprevalence of cutaneous HPV types and investigate factors associated with the seropositivity, and evaluate the association between seropositivity to cutaneous HPV types and the risk of development of EGLs. Several studies have reported the seroprevalence of mucosal HPV types (6, 11, 16 and 18) in the 4-valent HPV vaccine among men. However, few studies have reported the seroprevalence of the five additional HPV types (31, 33, 45, 52 and 58) in the recently approved 9-valent HPV (9vHPV) vaccine specifically among men across a broad age range. Baseline data on seroprevalence prior to vaccine introduction and dissemination are needed to establish the effectiveness of vaccines over time. Also, this study estimated the seroprevalence of 9vHPV vaccine types and investigated factors associated with the seropositivity among men residing in Brazil, Mexico, and the United States (U.S.). To estimate the seroprevalence of cutaneous HPV types and 9vHPV vaccine types, 600 men were randomly selected from the HPV Infection in Men (HIM) Study. To examine the association between seropositivity to cutaneous HPV types and development of EGLs, a case-control study of 163 incident EGL cases and 352 EGL-free controls nested in the HIM cohort was conducted. Cases were ascertained through visual inspection at each of up to 10 biannual clinical visits, confirmed through biopsy, and categorized into condyloma, suggestive of condyloma, penile intraepithelial neoplasia (PeIN) and other EGLs. Archived serum specimens were tested for antibodies against 14 cutaneous HPV types, β types (5, 8, 12, 14, 17, 22, 23, 24, 38 and 47), α type 27, γ type 4, µ type1 and ν type 41, and 9vHP types (6, 11, 16, 18, 31, 33, 45, 52 and 58) using a glutathione S-transferase (GST) L1-based multiplex serology assay. Socio-demographic and sexual behavior data were collected through a questionnaire. Binomial proportions were used to estimate seroprevalence, and logistic regression was used to examine factors associated with seropositivity. Overall, seroprevalence of ≥1 cutaneous HPV types was 65.4%, 1≥ β-HPV types was 39.0%, α-HPV 27 was 8.9%, γ-HPV 4 was 30.9%, µ-HPV 1 was 28.6%, and ν-HPV 41was 9.4%. Higher educational attainment was significantly associated with seropositivity to ≥1 cutaneous HPV types (adjusted odds ratio [AOR] 1.75 for ≥16 years of education vs. ≤12 years of education, 95% confidence interval [CI] 1.08-2.83), and seropositivity of ≥1 β-HPV types was significantly associated with increasing age (AOR 1.72 for men aged 31-44 years vs. men aged 18-30 years, 95% CI: 1.12–2.63,). Country of residence, circumcision status, and lifetime number of male anal sex partners were other factors significantly associated with various type-specific cutaneous HPV seropositivity. No statistically significant association was observed between grouped or individual cutaneous HPV seropositivity and the risk of development of EGLs across all pathological diagnoses. The seroprevalence of grouped and individual cutaneous HPV types was similar across different EGL categories and controls, with the most frequent types being ɤ-HPV 4, µ-HPV 1, and β-HPV 8. The seroprevalence of ≥1 9vHPV vaccine types was 28.3%, ≥1 high-risk types was 14.0%, five additional high-risk types was 11.2%, and low-risk types (6/11) was 17.4%. Compared to men with no male anal sex partners, men with ≥2 partners were two times more likely to be seropositive for grouped 9vHPV vaccine types, ≥1 high-risk types and ≥1 low-risk types, in addition to individual HPV types 6, 16, 33, and 58, with AORs ranging from 2.19 to 7.36. Older age, current smoking, and being single were other factors significantly positively associated with different grouped and type-specific seropositivity. In conclusion, our data show that exposure to cutaneous HPV was common in men although different risk factors were independently associated with grouped and type-specific cutaneous HPV seropositivity. It appears that exposure to cutaneous HPV is not likely to increase the risk of EGLs among men. Similarly, exposure to 9vHPV vaccine types was also common in men and seropositivity to 9vHPV vaccine types was positively associated with older age and lifetime number male anal sex partners.

Persistent infection with certain subtypes of Human papillomavirus (HPV) is a necessary cause of cervical cancer, the second most common cancer among women worldwide. Uptake of HPV vaccines in the targeted Canadian female population has been lower than anticipated. This study’s primary objective was to determine undergraduate women’s perceptions about HPV vaccination. A total of 401 female University of Ottawa undergraduate students completed a newly developed cross-sectional web survey. The prevalence of HPV vaccination was 49%. While the overall attitude towards receiving the vaccine was positive, vaccinated respondents had more favorable attitudes toward the vaccine. Lack of vaccine knowledge and cost were the primary barriers that have prevented HPV vaccination among non-vaccinated respondents. Offering HPV vaccination for women aged 18 to 25 presents a strategy for addressing suboptimal vaccination coverage in the targeted female population and may reduce health inequities demonstrated by variations in cervical cancer incidence within jurisdictions.

Papilomavírus (PVs) são vírus amplamente estudados, sendo enfatizada sua capacidade de infectar os tecidos epitelial e mucoso em diversos animais, incluindo humanos, causando lesões benignas que podem, ocasionalmente, resultar em câncer. Dentre os gêneros que infectam animais, os Deltapapillomavirus têm uma importância veterinária, ecológica e histórica, pois são capazes de infectar seu hospedeiro natural e outros animais. Por isso, esse trabalho contempla todos os tipos virais pertencentes aos Delta-PVs, incluindo sua história. Dentre as proteínas traduzidas pelos PVs, três são consideradas proteínas oncogênicas: E5, E6 e E7. Determinar a estrutura de uma proteína é crucial para a elucidação da sua função, possibilitando aplicações nas áreas de engenharia de proteínas, anotação genômica e desenho racional de fármacos. A estrutura tridimensional da proteína E6 de cada tipo viral pertencente ao gênero Deltapapillomavirus foi determinada por modelagem molecular por homologia. A história evolutiva dessas proteínas foi avaliada com base na geração de árvores filogenéticas e suas propriedades físico-químicas foram analisadas. Além disso, devido ao seu alto grau de conservação, a E6 demonstrou ser útil como um marcador molecular. Apesar de serem consideradas raras, foram observadas lesões papilomatosas em carneiros em uma fazenda do estado de São Paulo. Foi realizado o diagnóstico molecular dessas lesões. Os resultados mostraram pela primeira vez no mundo que, apesar de serem ovinos, o agente causador da papilomatose era um papilomavírus bovino, o BPV2, um Delta-PV. Logo, além de discutir os Delta-PVs, esta tese demonstra na prática a habilidade desse gênero em romper a barreira espécie-específica. / Papillomaviruses (PVs) are widely studied viruses, emphasizing their ability to infect the epithelial and mucosal tissues in several animals, including humans, causing benign lesions that may occasionally result in cancer. Among the genera that infect animals, Deltapapillomaviruses have a veterinary, ecological and historical importance because they are capable of infecting their natural host and other animals. Therefore, this work contemplates all viral types belonging to the Delta-PVs, including their history. Among the proteins translated by the PVs, three of them are considered oncogenic proteins: E5, E6 and E7. Determining the structure of a protein is crucial to the elucidation of its function, allowing applications in the areas of protein engineering, genomic annotation and rational design of drugs. The three-dimensional structure of the E6 protein of each viral type belonging to the genus Deltapapillomavirus was determined by molecular modeling by homology. The evolutionary history of these proteins was evaluated based on the generation of phylogenetic trees and their physicochemical properties were analyzed. In addition, due to its high degree of conservation, E6 has been shown to be useful as a molecular marker. Despite being considered rare, papillomas lesions were observed in sheep on a farm in the state of São Paulo. The molecular diagnosis of these lesions was performed. The results showed for the first time in the world that, despite being ovines, the causative agent of papillomatosis was a bovine papillomavirus, BPV2, a Delta-PV. Thus, in addition to discussing Delta-PVs, this thesis demonstrates in practice the ability of this genre to break the species-specific barrier.

BACKGROUND: Human Papillomavirus (HPV) is the most common sexually-transmitted infection in the U.S. and is associated with a number of cancers. A vaccine that can prevent 90% of HPV-associated cancers has been available since 2006, yet millions of young adults remain unvaccinated. Low vaccination uptake has been observed in cisgender sexual minority communities and less is known about HPV vaccination among transgender and gender nonbinary (TGNB) people. The aims of this dissertation were: (a) to identify facilitators for and barriers to HPV vaccination among gender minority people; (b) to compare HPV vaccination rates, HPV risk and situational factors like barriers to care, access to care, preventive care, HPV knowledge and Internet use in a sample of TGNB people and cisgender sexual minority people; and (c) to explore the association of online health information and HPV vaccination receipt among TGNB people compared to cisgender sexual minority people and determine if eHealth Literacy or general health literacy moderate this relationship. METHODS: The dissertation comprised three studies. First, an integrative review of the literature included searches of three electronic databases to identify and appraise studies that explore patient-, provider- and system-level HPV vaccination barriers among gender minority people. Second, guided by the Integrative Model of eHealth Use, a cross-sectional secondary analysis of The Population Research in Identities and Disparities for Equality (PRIDE) Study Annual Questionnaire 2018-19, compared the rate of HPV vaccination among TGNB and cisgender sexual minority people and described situation factors (e.g., barriers to care, access to care, preventive care), Internet use, HPV knowledge, HPV risk, and HPV vaccination among these communities. Third, a novel cross-sectional online survey of TGNB and cisgender sexual minority participants recruited from The PRIDE Study, also guided by the Integrative Model of eHealth Use, explored the association between online health information seeking and receipt of HPV vaccine, and whether eHealth literacy and/or general health literacy moderate this relationship. Statistical methods for the cross-sectional studies included prevalence ratios (PR) using robust Poisson statistics and multivariable logistic regression with post hoc Bonferroni-Holm correction. RESULTS: The integrative review identified six cross-sectional studies and one qualitative study that explored HPV vaccine barriers and facilitators among gender minority people. The majority of the studies included <10% gender minority participants. Key barriers to vaccination identified were misperceptions of risk at patient-level, bias towards vaccinating female assigned individuals at the provider-level and population effects of recommendations for girls-only at the policy-level. The cross-sectional secondary analysis of The PRIDE Study 2018-19 Annual Questionnaire and included N = 5,500 responses and found that: (a) the prevalence of ever receiving HPV vaccine was 1.2 times greater among TGNB participants than cisgender participants (PR 1.2; 95% CI, 1.1-1.3); (b) the prevalence of ever receiving HPV vaccine was 2.4 times greater among transgender men who were assigned female at birth compared to transgender women who were assigned male at birth (PR 2.4; 95% CI, 2.0-2.8); and (c) no differences in vaccination initiation and vaccination completion based on gender identity, sex assigned at birth, sex organs born with, or current sex organs. The cross-sectional novel online survey of PRIDE participants yielded N = 3,258 responses (response rate 19.6%). After controlling for covariates including age, race/ethnicity and educational attainment, we found that TGNB as compared to cisgender participants had increased odds (aOR=1.5=; 95% CI, 1.1-2.2) of reporting receipt of HPV vaccine ever and decreased odds (aOR=0.7; 95% CI, 0.5-0.9) of ever receiving of HPV vaccine when they looked for info on vaccines in the past year. Conversely, TGNB participants had over twice the odds (aOR=2.4; 95% CI, 1.1-5.6) of ever receiving HPV vaccine if they visited a social networking site like Facebook or Instagram in the past year. There were no moderating effects observed from eHealth or general health literacy. CONCLUSIONS: TGNB communities are understudied in terms of HPV vaccination and the existing literature shows misperceptions about the need of HPV vaccination among TGNB communities at both the patient and provider level. TGNB participants were more likely to have ever received HPV vaccine compared to cisgender sexual minority participants in the cross-sectional secondary analysis of The PRIDE Study 2018-19 Annual Questionnaire which may be attributed to high primary engagement in the cohort. Finally, online health information seeking about vaccines was associated with decreased receipt of HPV vaccine (ever) whereas social media use increased HPV vaccine receipt (ever) among TGNB participants compared to cisgender sexual minority participants. These conflicting findings suggest that the quality of online health information relating HPV vaccines, how, when and why TGNB people search for health information online may affect health behaviors like HPV vaccination. More research is warranted to explore how online health information seeking may influence personal health decision-making among TGNB communities.

Cervical Cancer is a preventable disease. Sadly it is a cause morbidity and mortality of women in poor socio-economic settings worldwide, largely due to avoidable factors. This amounts to a gross violation of the rights to life and access to healthcare of vulnerable populations of women. Awareness, sensitisation and mobilisation of the civil society could be crucial in influencing change in political will and healthcare policies to address the needs of HIV infected women, in particular, given their susceptibility to the development of cervical cancer. This work advocates for the South African government to further commit resources towards the prevention of cervical cancer, including hysterectomy in women at high risk of developing cervical cancer before it ensues. / Mini Dissertation (MPhil)--University of Pretoria, 2019. / Public Law / MPhil / Unrestricted