by Meng Chunling. / "September 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 143-159). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Em sete adolescentes com dermatomiosite (DM) juvenil (DMJ) foi avaliada a função gonadal através do estadiamento puberal, aspectos da sexualidade, exame físico da genitália e exames complementares: análise seminal (duas amostras com intervalo de um mês), anticorpos anti-espermatozóides, ultra-sonografia escrotal e dosagens hormonais (testosterona, hormônio estimulante do folículo, hormônio luteinizante, prolactina, T3, T4, T4 livre e TSH). Todos os pacientes apresentaram terazospermia, dois tiveram varicocele e um anticorpo anti-espermatozóide localizado em peça intermediária. A futura fertilidade destes pacientes é incerta e estudos de prevalência de função gonadal em populações de jovens e adultos do sexo masculino com DM são necessários / In seven adolescents with dermatomyositis (MD) juvenile (JDM), gonadal function was evaluated through the puberal estadiamento, aspects of the sexuality, examination of the genitalia, semen analysis (two semen samples over a period of one month), anti-sperm, testicular ultrasound and hormones (testosterone, follicle stimulating hormone, luteinizing hormone, prolactin, T3, T4, free T4 and TSH).

Conclusion. Taken together, paternal factors carried in ASG secretion affect genomic imprinting of developing embryos. The outcome of research work described here deepens our understanding of the role of ASG in maximizing reproductive performance mediated by regulating the epigenetic marks of the genome and in particular the imprinted genes. / Introduction. Our previous in vivo studies in golden hamster have shown the accessory sex glands (ASG) secretion facilitate the development of embryos to term but the underlying mechanism is still not clear. Since the deleterious effect caused by the lack of sperm exposure to ASG secretion is heritable to developing fetus and even after birth, we hypothesized that the paternal factor carried in ASG secretion may change the epigenetic regulation and in particular the imprinted genes of embryonic genome. / Materials and methods. Golden hamster and ICR mouse were used in this study. Hamster is a well-established animal model to study the effect of individual ASG but the genetic background of hamster is poorly known. To verify the specificity of our molecular probe and antibodies used in hamster, a mouse model was also established. Five groups of male hamsters and two groups of male mice were established by surgical treatment. In hamster, (SH) sham-operated, (VPX) ventral prostate-removed, (TX) all ASG-removed, (VPVX) castrated with ASG-removed except ventral prostate and (VX) castrated with intact ASG were established. In mouse, SH and VPX were established. In single-mating of hamster, male was copulated with female at estrus for 15 min. In double-mating of hamsters, female mated with each male for 10 min each. In single-mating of mouse, male was caged with female for 1 h. Epididymal sperm, uterine sperm, fertilized oocytes, pre-implantation embryos and fetuses at 13 days gestation (E13) were collected. Global DNA methylation of sperm, fertilized oocytes, early embryos and E13 fetuses were investigated by indirect immunofluorescence and DNA dot-blot using antibody against methylated DNA. Using the same technique, histone acetylation at lysine 5 residue was detected in male pronuclei of fertilized oocytes, protamine 1 and 2 content were detected in sperm, DNA methyltransferase 1, 3a and 3b activities were detected in early embryos. The crown-rump length and weight of fetuses were measured. Morphology was also examined under scanning electron microscope. Two sets of co-ordinately regulated but oppositely expressed imprinted genes Igf2/H19 and Dlk1/Gtl2 were investigated. H19 differentially methylated region (DMR) and Gtl2 promoter were examined by bisulfite sequencing in sperm and E13 fetuses. Expression of Igf2 and Dlk1 were examined by in situ hybridization and real-time PCR in pre-implantation embryos and E13 fetuses. / Results. Uterine sperm in VPX and TX groups showed no change of DNA methylation level and protamine 1 and 2 content. Fertilized oocytes in VPX and TX groups showed similar DNA methylation level as SH group in both hamster and mouse. Histone hypoacetylation was observed in male pronuclei of hamster but not in mouse. Early embryos in VPX and TX groups showed abnormal level of DNA methylation and Dnmt3b during embryo development in hamster. Replenishment of ASG secretion to sperm from VPX and TX group by double-mating restored the DNA methylation level to normal in early embryos. E13 fetuses of VPX and TX groups in hamster and VPX group in mouse showed DNA hypomethylation. E13 fetuses of VPX group in hamster showed increase in average crown-rump length and body weight with larger variations between individuals. One E13 fetus of VPX group in mouse showed polydactyly and malformation in the head. Real-time PCR showed abnormal expression of Igf2 and Dlk1 in both pre-implantation embryos and E13 fetuses of VPX and TX groups. Bisulfite sequencing showed hypermethylation of H19 DMR in VPX and TX groups of hamster and hypomethylation of Gtl2 promoter in VPX group of mouse. / "August 2007." / Adviser: Pak Ham Chow. / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4739. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 194-224). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.

Em sete adolescentes com dermatomiosite (DM) juvenil (DMJ) foi avaliada a função gonadal através do estadiamento puberal, aspectos da sexualidade, exame físico da genitália e exames complementares: análise seminal (duas amostras com intervalo de um mês), anticorpos anti-espermatozóides, ultra-sonografia escrotal e dosagens hormonais (testosterona, hormônio estimulante do folículo, hormônio luteinizante, prolactina, T3, T4, T4 livre e TSH). Todos os pacientes apresentaram terazospermia, dois tiveram varicocele e um anticorpo anti-espermatozóide localizado em peça intermediária. A futura fertilidade destes pacientes é incerta e estudos de prevalência de função gonadal em populações de jovens e adultos do sexo masculino com DM são necessários / In seven adolescents with dermatomyositis (MD) juvenile (JDM), gonadal function was evaluated through the puberal estadiamento, aspects of the sexuality, examination of the genitalia, semen analysis (two semen samples over a period of one month), anti-sperm, testicular ultrasound and hormones (testosterone, follicle stimulating hormone, luteinizing hormone, prolactin, T3, T4, free T4 and TSH).

O HPV é transmitido principalmente pelo contato sexual e as infecções causadas por tipos virais oncogênicos estão etiologicamente associadas com o desenvolvimento de câncer de colo de útero, vulva e ânus nas mulheres, câncer de pênis e ânus nos homens, e câncer de cabeça e pescoço em ambos os sexos. Além disso, as verrugas genitais e a rara, mas séria, papilomatose respiratória estão etiologicamente associadas aos HPVs de baixo risco 6 e 11. Ademais, os HPV-16 e 6 estão entre os tipos mais frequentemente detectados em homens, independentemente da origem da amostra estudada, ressaltando a importância epidemiológica do HPV-6. Até o momento, estudos de associação entre variantes moleculares de HPV e o desenvolvimento das doenças associadas foram realizados para os HPVs de alto-risco oncogênico, como os HPV-16 e -18. Em relação à prevalência dos HPVs de baixorisco oncogênico e as implicações da heterogeneidade viral, os dados existentes até o momento são escassos. Pelo exposto, este projeto tem por objetivo: (1) Determinar a prevalência das diferentes variantes moleculares de HPV-6 em esfregaços genitais e lesões genitais externas (LGE), especificamente em verrugas genitais (VGs), entre os participantes do estudo prospectivo multinacional da Infecção por HPV em homens (estudo HIM); (2) Verificar a associação entre a infecção por diferentes variantes moleculares de HPV-6 e o risco de desenvolvimento de LGE nos participantes do estudo HIM. Para atingir os objetivos propostos foram utilizados esfregaços genitais e amostras de verruga genital dos participantes HPV-6 positivos do estudo HIM. Nestas amostras, as variantes de HPV-6 foram caracterizadas através da amplificação por PCR e sequenciamento de um fragmento do gene L2. Isto permitiu classificar as amostras em todas as linhagens (A, B) e sub-linhagens (B1, B2, B3, B4, B5) de HPV-6 descritas. Neste estudo, as variantes da sub-linhagem B3 foram as mais prevalentes. A distribuição das variantes de HPV-6 diferiu entre os países e entre casos e controles. A prevalência das variantes B1 de HPV-6 estava aumentada em VGs e esfregaços genitais de casos em comparação aos controles. Diferenças entre a detecção de variantes B1 e B3 nas VG e no esfregaço genital precedente à lesão foram observadas. Foi encontrada uma associação significativa entre a detecção de variantes da sub-linhagem B1 de HPV-6 e o desenvolvimento de VGs. Em conclusão, variantes B1 de HPV-6 são mais prevalentes em esfregaços genitais normais que precedem o desenvolvimento de VGs. Ademais as variantes B1 conferem risco aumentado para o desenvolvimento de VGs. Estudos futuros são necessários para compreender o possível envolvimento aumentado de variantes B1 de HPV-6 na progressão para lesões clinicamente relevantes / HPV is primarily transmitted through sexual contact and infections caused by oncogenic viral types are etiologically associated with the development of cervical, vulvar and anal cancer, in women, penile and anal cancer in men, and head and neck cancer in both sexes. Moreover, genital warts and the rare, but serious, respiratory papillomatosis are etiologically associated with low-risk HPV types -6 and -11. Additionally, data obtained from different studies show that HPV types -16 and -6 are among the most frequently detected types in men, independently of the origin of the samples studied, underscoring the epidemiological relevance of HPV-6. To date, studies focusing on the association between HPV molecular variants and disease onset have been conducted on high-risk types such as -16 and -18. Regarding the prevalence of low-risk HPVs and the implications of their viral heterogeneity, date is still scarce. In light of these facts, the objectives of this project are to: (1) Determine the prevalence of HPV-6 molecular variants in genital swabs and external genital lesions (EGL), specifically genital warts (GW), among participants of the prospective and multinational HPV infection in men study (HIM study); (2) To verify the association between HPV-6 molecular variants infection and the risk of developing EGL among HIM study participants. To achieve the proposed objectives, genital swabs and genital wart samples from HPV-6 positive HIM study participants were used. In these samples, HPV-6 variants were characterized by PCR amplification followed by sequencing of an L2 gene fragment. This allowed for the classification of the samples into all described HPV-6 lineages (A, B) and sub-lineages (B1, B2, B3, B4, B5). In this study, variants belonging to B3 sub-lineage were the most prevalent. HPV-6 variants distribution differed between countries and between cases and controls. HPV-6 B1 variants prevalence was increased in GWs and genital swabs of cases compared to controls. Differences among B1 and B3 variants detection in GW and the preceding genital swab were observed. A significant association of HPV-6 B1 variants detection with GW development was found. In conclusion, HPV-6 B1 variants are more prevalent in normal genital swabs that precede GW development. Additionally, B1 variants confer an increased risk for GW development. Further research is needed to understand the possible increased involvement of B1 variants in the progression to clinically relevant lesions

O papilomavírus humano (HPV) é transmitido principalmente através do contato sexual e a infecção por estes vírus está fortemente associada ao desenvolvimento de tumores do colo do útero, da vulva e do ânus em mulheres, câncer do pênis e do ânus em homens, assim como tumores da cabeça e pescoço em ambos os sexos. Também há estudos em andamento para estimar a proporção de câncer de pele não-melanoma que podem ser atribuíveis às infecções por tipos virais pertencentes aos ramos cutâneos da filogenia do HPV. Os beta- (beta-) HPV vem sendo predominantemente isolados de tecidos cutâneos e sugere-se que façam parte da flora comensal humana. Entretanto, pouco se sabe sobre o papel destes nos sítios de detecção, seja em indivíduos imunosuprimidos como imunocompetentes. A fim de compreender a história natural dos HPV em homens, o Estudo da Infecção por HPV em homens (HIM Study) foi desenhado e conduzido entre 2005 e 2013 no Brasil, México e Estados Unidos (EUA). Em sua primeira triagem de amostras genitais, observou-se que 14,7% eram positivas para HPV, entretanto não correspondia a nenhuma das 37 sondas tipo-específicas para detecção dos principais beta- HPV. Após um protocolo de PCR fazendo uso de iniciadores genéricos, seguido por sequenciamento, observou-se um elevado número de tipos virais cutâneos nessas amostras. Perante isso, os objetivos deste trabalho foram (1) Determinar a prevalência de 43 tipos de beta-HPV em 729 homens participantes do estudo HIM que forneceram amostras anogenitais e orais em mesma visita de seguimento; (2) Identificar fatores demográficos e sexuais independentemente associados com a detecção de DNA destes tipos de HPV nos diferentes sítios anatômicos analisados. Para atingi-los, utilizou-se a metodologia Luminex atualmente bem estabelecida para genotipagem de beta-HPV. Dentre os homens genotipados, 557 (77,7%), 389 (54,3%) e 210 (29,3%) foram positivos para algum tipo de beta-HPV no região genital, do canal anal e da cavidade oral, respectivamente. Os tipos de beta-HPV mais prevalentes foram HPV-21, -22, -24 e -38 em todos os sítios anatômicos. Homens residentes no EUA (OR = 0,55, 95% intervalo de confiança [IC] de 0,38-0,80) e Brasil (OR = 0,49, 95% CI 0,33-0,73) foram significativamente menos propensos a serem detectados com algum beta-HPV no canal anal, comparado aos residentes no México. A idade foi marginalmente associada à maior prevalência de HPV na região do canal anal sendo que de homens mais velhos (31-44 anos, OR = 1,30, 95% CI 0,93-1,82; 45-70 anos, OR = 1,59, 95% CI 0,98-2,58) foram mais propensos a serem positivos para DNA de beta-HPV, comparado a homens mais jovens (18-30 anos). A prevalência de algum beta-HPV na cavidade oral também foi significativamente associada ao país de residência e idade. Fumantes (OR = 0,50, 95% CI 0.32-0.80) foram significativamente menos propensos a serem positivos para beta-HPV na cavidade oral do que os homens que nunca fumaram. A ausência de associação entre a detecção de beta-HPV e comportamentos sexuais específicos sugere o contato digital e auto-inoculação como rotas alternativas de transmissão desses vírus / HPV is primarily transmitted by sexual contact and infection by these viruses is strongly associated with the development of tumors in the cervix, vulva and anus in women, cancer of the penis and anus in men, as well as tumors in the head and neck in both genders. There are also ongoing studies ongoing to estimate the proportion of nonmelanoma skin cancer that may be attributable to infection by viral types from cutaneous branches of the phylogeny of HPV. Human beta papillomaviruses (beta-HPV) have been predominantly isolated from cutaneous tissues, and are thought to be part of the commensal flora. However, the role of beta-HPV detection in these sites is unknown, whether in immunosuppressed or immunocompetent individuals. In order to understand the natural history of HPV in men, the HPV Infection in Men Study (HIM Study) was designed and conducted between 2005 and 2013 in Brazil, Mexico and the United States (US). In a first screening of genital samples, it was observed that 14.7% were positive for HPV, but did not correspond to neither 37 type-specific probes for detection of major ?-HPVs. After a PCR protocol using of generic primers followed by sequencing, we observed a large number of cutaneous HPV types in these samples. For this reason, the objectives of this study were (1) To determine the prevalence of 43 types of beta-HPV in 729 male participants of the HIM study provided anogenital and oral samples in the same follow-up visit; (2) To identify demographic and sexual factors independently associated with DNA detection of these types of HPV in different anatomical sites analyzed. To achieve these objectives we used the currently well-established Luminex methodology for beta-HPV genotyping. Overall, 557 (77.7%), 389 (54.3%) and 210 (29.3%) men were positive for any beta-HPV type at the genital, anal canal and oral cavity, respectively. The most prevalent beta-HPV types were HPV-21, -22, -24 and -38 within all anatomic sites. Men from the US (OR= 0.55, 95% Confidence Interval [CI] 0.38-0.80) and Brazil (OR=0.49, 95% CI 0.33-0.73) were significantly less likely to have any beta-HPV at the anal canal than men from Mexico. Age was marginally associated with anal HPV prevalence with older men (31-44 years, OR=1.30, 95% CI 0.93-1.82; 45-70 years, OR=1.59, 95% CI 0.98-2.58) being more likely to have any beta-HPV at the anal canal compared to younger men (18-30 years). Prevalence of any beta-HPV at the oral cavity was also significantly associated with country of origin and age. Current (OR=0.50, 95% CI 0.32-0.80) smokers were significantly less likely to have beta-HPV at the oral cavity than men that never smoked. Lack of associations between beta- HPV detection and specific sexual behaviors suggests digital contact and autoinoculation as surrogate routes of transmission of these viruses

Cheung King Ho. / "August 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 140-158). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Chan Oi Chi. / "May 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 259-310) / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

O papilomavírus humano (HPV) é transmitido principalmente através do contato sexual e a infecção por estes vírus está fortemente associada ao desenvolvimento de tumores do colo do útero, da vulva e do ânus em mulheres, câncer do pênis e do ânus em homens, assim como tumores da cabeça e pescoço em ambos os sexos. Também há estudos em andamento para estimar a proporção de câncer de pele não-melanoma que podem ser atribuíveis às infecções por tipos virais pertencentes aos ramos cutâneos da filogenia do HPV. Os beta- (beta-) HPV vem sendo predominantemente isolados de tecidos cutâneos e sugere-se que façam parte da flora comensal humana. Entretanto, pouco se sabe sobre o papel destes nos sítios de detecção, seja em indivíduos imunosuprimidos como imunocompetentes. A fim de compreender a história natural dos HPV em homens, o Estudo da Infecção por HPV em homens (HIM Study) foi desenhado e conduzido entre 2005 e 2013 no Brasil, México e Estados Unidos (EUA). Em sua primeira triagem de amostras genitais, observou-se que 14,7% eram positivas para HPV, entretanto não correspondia a nenhuma das 37 sondas tipo-específicas para detecção dos principais beta- HPV. Após um protocolo de PCR fazendo uso de iniciadores genéricos, seguido por sequenciamento, observou-se um elevado número de tipos virais cutâneos nessas amostras. Perante isso, os objetivos deste trabalho foram (1) Determinar a prevalência de 43 tipos de beta-HPV em 729 homens participantes do estudo HIM que forneceram amostras anogenitais e orais em mesma visita de seguimento; (2) Identificar fatores demográficos e sexuais independentemente associados com a detecção de DNA destes tipos de HPV nos diferentes sítios anatômicos analisados. Para atingi-los, utilizou-se a metodologia Luminex atualmente bem estabelecida para genotipagem de beta-HPV. Dentre os homens genotipados, 557 (77,7%), 389 (54,3%) e 210 (29,3%) foram positivos para algum tipo de beta-HPV no região genital, do canal anal e da cavidade oral, respectivamente. Os tipos de beta-HPV mais prevalentes foram HPV-21, -22, -24 e -38 em todos os sítios anatômicos. Homens residentes no EUA (OR = 0,55, 95% intervalo de confiança [IC] de 0,38-0,80) e Brasil (OR = 0,49, 95% CI 0,33-0,73) foram significativamente menos propensos a serem detectados com algum beta-HPV no canal anal, comparado aos residentes no México. A idade foi marginalmente associada à maior prevalência de HPV na região do canal anal sendo que de homens mais velhos (31-44 anos, OR = 1,30, 95% CI 0,93-1,82; 45-70 anos, OR = 1,59, 95% CI 0,98-2,58) foram mais propensos a serem positivos para DNA de beta-HPV, comparado a homens mais jovens (18-30 anos). A prevalência de algum beta-HPV na cavidade oral também foi significativamente associada ao país de residência e idade. Fumantes (OR = 0,50, 95% CI 0.32-0.80) foram significativamente menos propensos a serem positivos para beta-HPV na cavidade oral do que os homens que nunca fumaram. A ausência de associação entre a detecção de beta-HPV e comportamentos sexuais específicos sugere o contato digital e auto-inoculação como rotas alternativas de transmissão desses vírus / HPV is primarily transmitted by sexual contact and infection by these viruses is strongly associated with the development of tumors in the cervix, vulva and anus in women, cancer of the penis and anus in men, as well as tumors in the head and neck in both genders. There are also ongoing studies ongoing to estimate the proportion of nonmelanoma skin cancer that may be attributable to infection by viral types from cutaneous branches of the phylogeny of HPV. Human beta papillomaviruses (beta-HPV) have been predominantly isolated from cutaneous tissues, and are thought to be part of the commensal flora. However, the role of beta-HPV detection in these sites is unknown, whether in immunosuppressed or immunocompetent individuals. In order to understand the natural history of HPV in men, the HPV Infection in Men Study (HIM Study) was designed and conducted between 2005 and 2013 in Brazil, Mexico and the United States (US). In a first screening of genital samples, it was observed that 14.7% were positive for HPV, but did not correspond to neither 37 type-specific probes for detection of major ?-HPVs. After a PCR protocol using of generic primers followed by sequencing, we observed a large number of cutaneous HPV types in these samples. For this reason, the objectives of this study were (1) To determine the prevalence of 43 types of beta-HPV in 729 male participants of the HIM study provided anogenital and oral samples in the same follow-up visit; (2) To identify demographic and sexual factors independently associated with DNA detection of these types of HPV in different anatomical sites analyzed. To achieve these objectives we used the currently well-established Luminex methodology for beta-HPV genotyping. Overall, 557 (77.7%), 389 (54.3%) and 210 (29.3%) men were positive for any beta-HPV type at the genital, anal canal and oral cavity, respectively. The most prevalent beta-HPV types were HPV-21, -22, -24 and -38 within all anatomic sites. Men from the US (OR= 0.55, 95% Confidence Interval [CI] 0.38-0.80) and Brazil (OR=0.49, 95% CI 0.33-0.73) were significantly less likely to have any beta-HPV at the anal canal than men from Mexico. Age was marginally associated with anal HPV prevalence with older men (31-44 years, OR=1.30, 95% CI 0.93-1.82; 45-70 years, OR=1.59, 95% CI 0.98-2.58) being more likely to have any beta-HPV at the anal canal compared to younger men (18-30 years). Prevalence of any beta-HPV at the oral cavity was also significantly associated with country of origin and age. Current (OR=0.50, 95% CI 0.32-0.80) smokers were significantly less likely to have beta-HPV at the oral cavity than men that never smoked. Lack of associations between beta- HPV detection and specific sexual behaviors suggests digital contact and autoinoculation as surrogate routes of transmission of these viruses

O HPV é transmitido principalmente pelo contato sexual e as infecções causadas por tipos virais oncogênicos estão etiologicamente associadas com o desenvolvimento de câncer de colo de útero, vulva e ânus nas mulheres, câncer de pênis e ânus nos homens, e câncer de cabeça e pescoço em ambos os sexos. Além disso, as verrugas genitais e a rara, mas séria, papilomatose respiratória estão etiologicamente associadas aos HPVs de baixo risco 6 e 11. Ademais, os HPV-16 e 6 estão entre os tipos mais frequentemente detectados em homens, independentemente da origem da amostra estudada, ressaltando a importância epidemiológica do HPV-6. Até o momento, estudos de associação entre variantes moleculares de HPV e o desenvolvimento das doenças associadas foram realizados para os HPVs de alto-risco oncogênico, como os HPV-16 e -18. Em relação à prevalência dos HPVs de baixorisco oncogênico e as implicações da heterogeneidade viral, os dados existentes até o momento são escassos. Pelo exposto, este projeto tem por objetivo: (1) Determinar a prevalência das diferentes variantes moleculares de HPV-6 em esfregaços genitais e lesões genitais externas (LGE), especificamente em verrugas genitais (VGs), entre os participantes do estudo prospectivo multinacional da Infecção por HPV em homens (estudo HIM); (2) Verificar a associação entre a infecção por diferentes variantes moleculares de HPV-6 e o risco de desenvolvimento de LGE nos participantes do estudo HIM. Para atingir os objetivos propostos foram utilizados esfregaços genitais e amostras de verruga genital dos participantes HPV-6 positivos do estudo HIM. Nestas amostras, as variantes de HPV-6 foram caracterizadas através da amplificação por PCR e sequenciamento de um fragmento do gene L2. Isto permitiu classificar as amostras em todas as linhagens (A, B) e sub-linhagens (B1, B2, B3, B4, B5) de HPV-6 descritas. Neste estudo, as variantes da sub-linhagem B3 foram as mais prevalentes. A distribuição das variantes de HPV-6 diferiu entre os países e entre casos e controles. A prevalência das variantes B1 de HPV-6 estava aumentada em VGs e esfregaços genitais de casos em comparação aos controles. Diferenças entre a detecção de variantes B1 e B3 nas VG e no esfregaço genital precedente à lesão foram observadas. Foi encontrada uma associação significativa entre a detecção de variantes da sub-linhagem B1 de HPV-6 e o desenvolvimento de VGs. Em conclusão, variantes B1 de HPV-6 são mais prevalentes em esfregaços genitais normais que precedem o desenvolvimento de VGs. Ademais as variantes B1 conferem risco aumentado para o desenvolvimento de VGs. Estudos futuros são necessários para compreender o possível envolvimento aumentado de variantes B1 de HPV-6 na progressão para lesões clinicamente relevantes / HPV is primarily transmitted through sexual contact and infections caused by oncogenic viral types are etiologically associated with the development of cervical, vulvar and anal cancer, in women, penile and anal cancer in men, and head and neck cancer in both sexes. Moreover, genital warts and the rare, but serious, respiratory papillomatosis are etiologically associated with low-risk HPV types -6 and -11. Additionally, data obtained from different studies show that HPV types -16 and -6 are among the most frequently detected types in men, independently of the origin of the samples studied, underscoring the epidemiological relevance of HPV-6. To date, studies focusing on the association between HPV molecular variants and disease onset have been conducted on high-risk types such as -16 and -18. Regarding the prevalence of low-risk HPVs and the implications of their viral heterogeneity, date is still scarce. In light of these facts, the objectives of this project are to: (1) Determine the prevalence of HPV-6 molecular variants in genital swabs and external genital lesions (EGL), specifically genital warts (GW), among participants of the prospective and multinational HPV infection in men study (HIM study); (2) To verify the association between HPV-6 molecular variants infection and the risk of developing EGL among HIM study participants. To achieve the proposed objectives, genital swabs and genital wart samples from HPV-6 positive HIM study participants were used. In these samples, HPV-6 variants were characterized by PCR amplification followed by sequencing of an L2 gene fragment. This allowed for the classification of the samples into all described HPV-6 lineages (A, B) and sub-lineages (B1, B2, B3, B4, B5). In this study, variants belonging to B3 sub-lineage were the most prevalent. HPV-6 variants distribution differed between countries and between cases and controls. HPV-6 B1 variants prevalence was increased in GWs and genital swabs of cases compared to controls. Differences among B1 and B3 variants detection in GW and the preceding genital swab were observed. A significant association of HPV-6 B1 variants detection with GW development was found. In conclusion, HPV-6 B1 variants are more prevalent in normal genital swabs that precede GW development. Additionally, B1 variants confer an increased risk for GW development. Further research is needed to understand the possible increased involvement of B1 variants in the progression to clinically relevant lesions