Thesis (Ph. D.)--Oregon State University, 2007. / Printout. Includes bibliographical references. Also available on the World Wide Web.

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BENÍCIO, Givanildo Carneiro. Lesão intra-epitelial e DNA-HPV anal e fatores de risco associados em mulheres com lesão intra-epitelial genital HPV induzido 2013. 64 f. Dissertação (Mestrado em Patogia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2013. / Submitted by denise santos (denise.santos@ufc.br) on 2014-08-28T13:11:35Z No. of bitstreams: 1 2013_dis_gcbenicio.pdf: 968069 bytes, checksum: f8929b9a6399621de485eb3b113755e8 (MD5) / Approved for entry into archive by denise santos(denise.santos@ufc.br) on 2014-08-28T13:13:40Z (GMT) No. of bitstreams: 1 2013_dis_gcbenicio.pdf: 968069 bytes, checksum: f8929b9a6399621de485eb3b113755e8 (MD5) / Made available in DSpace on 2014-08-28T13:13:40Z (GMT). No. of bitstreams: 1 2013_dis_gcbenicio.pdf: 968069 bytes, checksum: f8929b9a6399621de485eb3b113755e8 (MD5) Previous issue date: 2013 / The anal cancer, which corresponds to 4% of all malignant neoplasms of the lower digestive tract, has been associated with HPV. There is a predominance of anal cancer in women (1.5 out of 5 times). The objectives of the study were: to evaluate the frequency of low and high oncogenic risk DNA-HPV, and of anal intraepithelial atypia in liquid-based cytology (SurePath BD) among immunocompetent women with genital intraepithelial lesions, and to identify the related risk factors. A prospective controlled study of quantitative, exploratory and descriptive nature was conducted in the clinic of Maternidade Escola Assis Chateaubriand (Maternity School) of the Ceará Federal University from August 2011 to September 2012. One hundred and fifty women submitted to genitoscopy in the Clinic of Lower Genital Tract Pathology and Colposcopy (PTGIC) with a history of HPV-induced lesions were included in the study. A standard questionnaire was applied. The patients underwent the procedure of anal cytology collection using the kit of SurePath liquid-based cytology (BD®) and then the samples were sent to the cytopathology laboratory for cytology slides preparation and DNA-HPV detection through the 2nd generation Hybrid Capture method. The data were analyzed using GraphPad Prism 6.0 software, applying the Student t test for nominal variables and the Fisher exact test for quantitative variables. The age ranged from 17 to 68 years (mean = 33.8 + 14.28) in the study group including women with genital intraepithelial lesions and from 19 to 75 years (mean = 40.48 + 15.1) in the control group with women with no genital lesion. The practice of anal intercourse occurred in 44 (55%) women in the study group and 34 (48.7%) in the control group. Analyzing the cytological atypia (ASC-US and LSIL), 30% of women with genital HPV lesions showed the presence of changes in cells of the anal canal. Lesions of perineum and perianus (p = 0.0003), vulva (p = 0.0157) and uterine cervix (p = 0.0223) were associated with anal cytological atypia. There was no significant association between DNA-HPV in the groups. It is concluded that the anal cytological atypia was frequent among women with perianal, vulva and uterine cervix lesions suggesting the need for screening anal intraepithelial lesions among immunocompetent individuals. / O câncer de ânus, que corresponde a 4% de todas as neoplasias malignas do trato digestivo baixo, tem sido associado ao HPV. O câncer do canal anal tem como predominância as mulheres (1,5 a 5 vezes). Foram objetivos do estudo: Avaliar a frequência de DNA-HPV de baixo e alto risco oncogênico, e de lesão intra-epitelial anal por citologia em meio líquido (SurePath BD) entre mulheres imunocompetentes com lesão intra-epitelial genital, bem como identificar os fatores de risco associados Foi realizado um estudo prospectivo controlado de natureza quantitativa, exploratória e descritiva no ambulatório da Maternidade Escola Assis Chateaubriand da Universidade Federal do Ceará de agosto de 2011 a setembro de 2012. Foram incluídas 150 mulheres, submetidas à genitoscopia no Ambulatório de Patologia do Trato Genital Inferior e Colposcopia (PTGIC), com historia de lesões genitais HPV induzidas onde foram obtidas informações, por meio de um questionário padrão. As pacientes foram submetidas ao procedimento de coleta de citologia anal utilizando o kit de citologia em meio líquido SurePath da empresa BD com pesquisa de DNA HPV pelo método de Captura Híbrida de 20 geração. Os dados foram analisados utilizando o software Graphpad Prism 6.0, aplicando o teste t de Student para as variáveis nominais e o teste exato de Fisher para as variáveis quantitativas. A idade variou de 17 a 68 anos (33,8 +14,28) no grupo de estudo, incluindo mulheres com lesão intra-epitelial genital e de 19 a 75 anos (40,48 + 15,1) no grupo controle com mulheres sem lesão genital. A prática do coito anal ocorreu em 44 (55%) das mulheres no grupo de estudo e por 34 (48,7%) no grupo controle. Analisando as atipias citológicas (ASC-US e LSIL), em 30% das mulheres com lesão genital por HPV mostraram presença de alteração em células do canal anal por citologia em meio líquido. As Lesões de Períneo e Perianus (p= 0.0003), Vulva (p= 0.0157) e Colo Uterino (p=0.0223) mostram-se associadas com as atipias citológicas anais no estudo. Não houve associação significativa entre DNA HPV e os grupos envolvidos na pesquisa, embora a tipificação do risco oncogênico apresentou-se com maior percentual nas mulheres com Lesão genital. Conclui-se que a atipia citológica anal mostrou-se freqüente entre mulheres com lesões perianais, vulvares e de colo uterino sugerindo a necessidade de rastreio de lesão intra-epitelial anal entre imunocompetentes.

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Made available in DSpace on 2016-08-29T15:34:47Z (GMT). No. of bitstreams: 1 tese_4464_.pdf: 3204606 bytes, checksum: a23da35b5188c96d619b059f83d1577a (MD5) Previous issue date: 2010-12-15 / Os HPV são vírus epiteliotrópicos que infectam tecido cutâneo ou mucoso e estão relacionados com desenvolvimento de lesões que, no trato genital, variam de verrugas ao câncer cervical invasivo. As lesões são causadas por diferentes tipos de HPV, que são classificados em baixo e alto risco conforme sua associação com câncer cervical. Sabe-se que mulheres positivas para HIV são mais acometidas por infecções por HPV e estão mais propensas ao desenvolvimento de câncer cervical. O objetivo desse estudo foi avaliar a frequência de tipos de HPV em mulheres soropositivas e soronegativas para HIV. Para isso foram analisadas amostras de escovado cervical, mantidas congeladas, de mulheres conhecidamente positivas para HPV (n=87), atendidas no Centro de Referência DST/AIDS, em Vitória-ES, no período de março a dezembro de 2006. O DNA das amostras foi extraído utilizando kit comercial QIAamp® DNA Mini Kit ou através do método de isotiocinanato de guanidina e sílica. DNA do HPV foi amplificado por PCR utilizando os iniciadores degenerados MY09/MY11 e a genotipagem foi realizada por Restriction Fragment Length Polymorphism (RFLP) e por Reverse Line Blot (RLB). Do total de amostras, 97,7% foram genotipadas e 31 tipos distintos detectados: 6, 11, 13, 16, 18, 26, 31, 31b, 32, 33, 34, 35, 42, 44, 51, 52, 53, 55, 56, 58, 59, 61, 62, 64, 66, 68, 71, 81, 82, 83 e 84. O tipo mais prevalente foi o HPV16, tanto nas mulheres soropositivas quanto nas soronegativas para HIV, seguido pelos tipos 6, 53 e 11. O tipo 13, incomum em amostras cervicais, foi observado nesse estudo, porém a quantidade de amostras não foi suficiente para a realização de seqüenciamento para a confirmação deste tipo viral. Os tipos oncogênicos foram mais comuns nas amostras de mulheres soropositivas para HIV, porém com número semelhante e o número de infecções múltiplas foi maior entre as mulheres HIV positivas. Este estudo revelou uma grande diversidade de tipos de HPV na região. PALAVRAS CHAVES: Human papillomavirus (HPV), Human Immunodeficiency virus (HIV), Restriction Fragment Length Polymorphism (RFLP), Reverse Line Blot (RLB).

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Orientadores: Marcelo Menossi Teixeira, Rodrigo Franco de Carvalho / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-25T18:01:39Z (GMT). No. of bitstreams: 1 Modolo_DiegoGrando_D.pdf: 3351414 bytes, checksum: 2f6c8310f0efbb6e6f3d2e48e34de879 (MD5) Previous issue date: 2014 / Resumo: O Brasil é conhecido por ter o segundo maior efetivo bovino e por ser o maior exportador de carne bovina no mundo. Dentre os problemas que afetam a pecuária nacional está a papilomatose bovina, uma doença infecto contagiosa causada pelo papilomavírus bovino (BPV). Diversas doenças de alto impacto econômico não só na pecuária nacional mas também mundial estão associadas ao BPV, sendo que ainda não existe uma vacina que possa prevenir o alastramento da doença e nem métodos eficázes de tramento. A proteína L1 do capsideo do BPV tipo 1 é uma forte candidata para ser utilizada na formulação vacinal por ser altamente imunogênica e ter a capacidade de formar, sozinha, partículas "virus-like" (VLPs). Devido a incapacidade de se multiplicar papilomavírus "in vitro", a utilização de sistemas de produção de proteínas recombinantes é a melhor estratégia para produção de proteínas virais em larga escala que possam ser utilizadas em formulações vacinais ou em testes de diagnósticos. Neste trabalho desenvolvemos uma plataforma de produção e purificação da proteína recombinante L1 em bactéria. A proteína L1 recombinante foi purificada por cromatografia de troca iônica e foi possível obter frações em alto nível de pureza. Também produzimos plantas transgênicas visando a produção da proteína L1. A transformação genética de plantas foi confirmada por PCR e RT-PCR, mas devido a inespecificidade dos anticorpos comerciais disponíveis e a uma possível baixa expressão do gene L1 em plantas, não foi possível confirmar a expressão da proteína recombinante. A proteína L1 obtida em bactérias poderá ser analisada como vacina e bem como na obtenção de anticorpos mais específicos e na produção de testes de diagnósticos. O conhecimento obtido neste trabalho poderá ser adaptado no desenvolvimento de outras vacinas de importância socio-econômica. / Abstract: Brazil is known as the largest exporter of beef and for having the second largest cattle herd in the world. Several illness that affect the national cattle industry are associated to the bovine papillomatosis, an infectious disease caused by Bovine Papillomavirus (BPV). Althought the economic impacts of these diseases affect the livestock at a global scale, there is no BPV vaccine or effective treatment methods available yet. The L1 capsid protein of BPV type 1 is a good candidate to be used in a vaccine formulation due its high immunogenicity and the ability to form virus-like particles (VLPs). Due to the inability to multiply papillomavirus in vitro, the use of recombinant protein production systems is the best strategy to produce viral proteins in large scale that can be used in vaccine formulations or for diagnosis testing. In this work, we developed a bacteria expression system to produce the recombinant L1 protein. The recombinant L1 protein was purified by ion exchange chromatography and highly purified fractions of L1 were obtained. We also obtained transgenic plants to produce the L1 protein. The genetic transformation of plants was confirmed by PCR and RT-PCR. Due to lack of specificity of commercial antibodies used in this study and a possible low expression of the L1 gene in plants, it was not possible to confirm the accumulation of the recombinant protein. The protein obtained in bacteria can be evaluated as vaccine as well as in the production of more specific antibodies and diagnosis tests. The knowledge obtained in this work can be adapted in the development of vaccines for other important socio-economic diseases / Doutorado / Genetica Vegetal e Melhoramento / Doutor em Genetica e Biologia Molecular

Background: The HPV vaccine is a primary prevention method available to reduce the burden of HPV-related cancers and genital warts. The vaccine is currently approved for catch-up vaccination among women 18 to 26 years of age. Despite this recommendation, the rate of vaccine uptake among this group is considerably low (~34% uptake). One demographic characteristic that is consistently reported as a risk factor for non-vaccination is relationship status, specifically married or monogamous relationships. While the epidemiological data confirm this association, there is a lack of understanding how this risk factor operates. By elucidating the mechanism for this risk factor, HPV vaccine uptake among this consistently unvaccinated group could be improved. Purpose: The purpose of this study was to understand how young adult women’s relationship status influence informational needs, motivations, and behavioral skills related to HPV vaccination. This objective was achieved through the following specific aims: (1) assess how relationship status affects primary reasons for non-vaccination among 18 to 26 year old women; and (2) understand how relationship status frames HPV vaccine decision-making among 18 to 26 year old women. Methods: To effectively achieve these specific aims, a concurrent mixed-methods study design was conducted. In Phase I, a secondary data analysis using the 2010 National Health Interview Survey was employed to determine if women in relationships are less likely to be interested in vaccination and identify the primary reasons (e.g., misinformation, motivations, behavioral skills) for non-vaccination among different relationship status categories. In Phase II, in-depth interviews were conducted with a sample (N=50) of 18 to 26 year old women at the University of South Florida, stratified by relationship status and vaccination status. A comparative thematic analysis was conducted to determine if there were differences in informational needs, motivations, behavioral skills, and HPV vaccine decision-making between the groups. Results: Using NHIS 2010 data, women who were living with a partner (PR 1.44 95%CI 1.07-1.87) and never married (PR 1.41 95%CI 1.12-1.73) were less likely to be interested in HPV vaccination compared women who were married. Moreover, primary reasons for non-vaccination differed significantly by relationship status group (p Conclusion: This study found that relationship status impacts HPV vaccine decision-making among young adult women. Specifically, it operates by modifying risk perceptions for HPV, which serve as barriers to vaccination. Young adult women have the knowledge and behavioral skills necessary to access and understand the importance of HPV vaccination; however, women were unable to accurately perceive their risk for HPV, resulting in impaired motivation for vaccination. A potential approach to address this issue is the use of health literacy. Future research should integrate health literacy techniques with healthcare providers serving this population to assist in the evaluation process for risk of HPV. This will facilitate shared decision-making and patient-provider communication surrounding the HPV vaccine. This can ultimately promote HPV vaccination among young adult women and reduce the morbidity and mortality of HPV-related diseases.

Human papillomavirus (HPV) is a double-stranded DNA virus, typically infecting mucosal or cutaneous epithelial keratinocytes. Today, more than 118 different HPV types have been formally described. Sexual transmission of mucosal HPVs is very common and generally asymptomatic, but HPV infection can be associated with benign lesions such as condylomata acuminata or, in rare cases, with malignant lesions such as cervical cancer. Two prophylactic vaccines are currently available in Europe, protecting against HPV-16 and HPV-18 (Cervarix&63720;) or against HPV-6, HPV-11, HPV-16 and HPV-18 (Gardasil&63720;). In order to assess the impact of the vaccination program, it is mandatory to obtain geographically widespread date on the baseline HPV prevalence and type distribution in cervical samples from women, presenting or not, normal or abnormal cytologic or histologic results. We undertook an epidemiological study in the Capital Region of Brussels to determine the HPV prevalence and type-distribution in 1526 cervical samples of women presenting a cytology within normal limits (WINL), atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intra-epithelial lesions (LSIL), high-grade squamous intra-epithelial lesions (HSIL) or invasive cervical cancer (ICC). The HPV prevalence was 10.8% (95%CI: 8.8-12.8) for NILM, 34.5% (95%CI: 28.3-40.8) for ASC-US, 54.0% (95%CI: 47.4-60.6) for LSIL and 100% for HSIL and ICC. With an HPV-16 and HPV-18 prevalence of 63.3% (95%CI: 44.1-67.7) and 73.5% (95%CI: 63.0-84.0) in mono-infected HSIL and ICC, respectively, HPV 16/18 L1 VLP vaccines would be expected to significantly reduce the management and treatment of women suffering from HSIL and ICC in the Capital Region of Brussels. We also detected HPV-30, HPV-53, HPV-66 and HPV-68 in mono-infected HSIL and ICC samples, possibly providing arguments for the reconsideration of the carcinogenicity of these types. <p>Vertical transmission of HPV was also previously reported, but in most cases one could not exclude a placental contamination by HPV positive cells from an infected birth canal. In order to confirm that the placenta can be infected with HPV, we analysed residual cells from 35 transabdominally obtained placental samples from pregnant women undergoing chorionic villous sampling for screening of suspected foetal abnormalities and found that two samples were positive for HPV-16 and HPV-62, respectively. The clinical importance of these results remains to be elucidated, but the previously observed association between placental HPV infection and pregnancy loss might gain further in importance. HPV gene regulation in placental trophoblastic cells has not been studied so far. We studied the HPV-16 early gene expression regulation in transiently transfected monolayer cultured trophoblastic cells with an HPV-16 long control region (LCR) driven reporter plasmid. We observed important differences in constitutive HPV-16 LCR activities between trophoblastic cell lines and could identify progesterone as an important inducer of HPV-16 early gene expression. Steroid hormones are induced during pregnancy and could therefore lead to an enhanced expression of the E5, E6 and E7 proteins upon placental HPV infection. Since these proteins were previously shown to affect trophoblast adhesion, survival, migration and invasion, their enhanced expression might eventually contribute to pregnancy loss. We furthermore found that the transcription of episomally maintained HPV-16 is not regulated by E2 or E1, but by E5, E6 and/or E7. <p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

Objective: To determine the general and genotype-specific prevalence of HPV and to identify potential risk factors for the infection in a population-based screening of Peruvian women. Results: A total of 524 samples were analyzed by PCR and a total of 100 HPV positive samples were found, of which 89 were high-risk, 19 were probably oncogenic, 9 were low-risk and 27 other HPV types. The 26–35 and 36–45 age groups showed the highest proportion of HPV positive samples with a total of 37% (37/100) and 30% (30/100), respectively. Moreover, high-risk HPV was found in 33.7% of both groups and probably oncogenic HPV in 52.6% and 31.6%, respectively. High-risk HPV were the most frequent types identified in the population studied, being HPV-52, HPV-31 and HPV-16 the most commonly detected with 17.6%, 15.7% y 12.9%, respectively. Demographic characteristics and habits were assessed in the studied population. A total of 62% high-risk HPV were detected in married/cohabiting women. Women with two children showed the highest proportion (33.8%) of high-risk HPV, followed by women with only one child (26.9%). Those women without history of abortion had a higher frequency of high-risk HPV (71.9%), followed by those with one abortion (25.8%). / Revisión por pares