Genetic Epidemiology of HPV Infection Outcome in Men

描述（由研究者提供）：人乳头瘤病毒（HPV）持续感染主要导致男性和女性的癌前病变和癌症病变，也可能影响HPV在性伴侣中的传播，因此是一种重要的“中间表型”。“迄今为止，HPV病因学研究的大部分工作都集中在女性身上。鉴于男性在将HPV传播给女性性伴侣沿着生殖器疣和几种癌症的公共卫生负担方面很重要，了解男性HPV的自然史将使男性和女性都受益。本研究的目的是检验宿主基因差异影响HPV在男性中持续存在的假设。虽然HPV持续存在的机制尚不清楚，但一些研究涉及免疫逃避，涉及宿主免疫应答的遗传介导的决定因素。HPV在女性中的遗传影响已被报道，我们建议在男性的背景下测试这一假设。我们与来自UAB和莫菲特癌症中心和研究所的研究人员合作的团队拥有丰富的经验和专业知识，为评估男性HPV感染结果的遗传效应提供了独特的机会。对于这项新的研究，我们将利用来自500名白人男性的数据，这些数据嵌套在男性HPV感染（HIM）中，这是唯一的男性多国前瞻性研究，包括4299名参与者，18-70岁，居住在美国南部佛罗里达，巴西圣保罗和墨西哥库埃尔纳瓦卡。我们将确定250名在获得后6个月内清除HPV 16的个体和另一组250名HPV 16持续超过12个月的个体，并使用免疫芯片对免疫相关基因中的变体进行基因分型（从感染性和自身免疫性疾病的关联研究中编译的约200，000个SNP）。我们将进行逻辑回归类型的遗传模型，以检查两组中遗传多态性的差异分布，将多种合并感染与每种HPV类型的相关性作为个体结果。研究的三个具体目的是：1）从250名患有持续性高血压的男性中在招募访视时收集的存档全血中提取基因组DNA。（e 12个月）生殖器HPV 16感染和250例一过性（仅1x检测）生殖器HPV 16; 2）使用免疫芯片阵列对所有500个样品进行基因分型;和3）进行统计分析以鉴定与生殖器HPV 16 DNA清除和持续相关的遗传变异据我们所知，这将是迄今为止第一次对男性HPV感染结果进行免疫遗传学研究。这项研究的任何信息数据都将填补男性HPV发病机制的免疫学效应的差距，并可能有助于确定适合男性及其伴侣特定治疗方法的分子特征。

DESCRIPTION (provided by investigator): Persistent infection with human papillomavirus (HPV) causes essentially pre-cancerous and cancer lesions in both men and women and also likely influences HPV transmission within sexual partners and thus is an important "intermediate phenotype." To date, most efforts in etiological research of HPV have focused in women. Given that men are important in transmitting HPV to their female sexual partners along with the public health burden of genital warts and several cancers, understanding the natural history of HPV in men would benefit both men and women. The purpose of this study is to test the hypothesis that differences in host genes influence HPV persistence in men. Although the mechanism for HPV persistence is unknown, several studies implicate immune evasion, involving genetically mediated determinants of the host immune response. Genetic influences of HPV in women have been reported and we propose test this hypothesis in the context of men. Our collaborative team with investigators from UAB and Moffitt Cancer Center and Research Institute has the experience and expertise that provides a unique opportunity to evaluate the genetic effects with well- documented HPV infection outcomes in men. For this new investigation, we will draw upon data from 500 Caucasian men nested within the HPV infection in Men (HIM), the only multi-national prospective study of men, which consists of 4299 participants, 18-70 years residing in southern Florida, USA, Sao Paulo, Brazil and Cuernavaca, Mexico. We will identify 250 individuals who cleared HPV16 within 6 months after acquisition and another set of 250 individuals in whom HPV16 has persisted for over 12 months and perform genotyping of variants in immune-related genes using the ImmunoChip ((~200,000 SNPs compiled from association studies of infectious and autoimmune diseases). We will perform a logistic regression type of genetic models to examine differential distribution of the genetic polymorphisms in the two groups, accounting for correlations of multiple co-infections with each HPV type as an individual outcome. Three specific aims of the study are: 1) Extract genomic DNA from archived whole blood collected at the enrollment visit among 250 men with persistent (e 12 months) genital HPV 16 infection and 250 with transient (1x detection only) genital HPV 16; 2) Genotype all 500 samples using the ImmunoChip array; and 3) Conduct statistical analyses to identify genetic variants associated with genital HPV 16 DNA clearance and persistence To our knowledge, this would be the first immunogenetic study of HPV infection outcome among men, to date. Any informative data from this study would fill in the gap of immunological effects with HPV pathogenesis in men and may help identify molecular signatures amenable to specific therapeutic approaches in men and their partners.