Factors associated with persistent anal human papillomavirus infection among men

描述（由申请人提供）：肛门癌主要由致癌的人乳头瘤病毒（HPV）类型引起。致癌性HPV感染的持续存在是最重要的早期生物学事件，标志着癌前肛门上皮内瘤变发展的风险增加。 在美国，艾滋病毒阴性的男男性行为者（MSM）的肛门癌年发病率比女性宫颈癌发病率高出数倍。目前还不清楚为什么只有一些MSM有持续的肛门HPV感染，从而增加了肛门癌的风险。这些数据现在特别重要，原因有两个：1）目前的HPV疫苗不推荐用于男孩和男性，2）目前的疫苗不允许在26岁以上的男性中使用。因此，更全面地了解持续性肛门HPV感染对于MSM中肛门癌干预措施的发展非常重要。 莫菲特癌症中心是唯一的定位为这项研究的结果，其收集和存档的肛门 男性人类乳头瘤病毒研究（HIM研究：NIH R 01 CA 098803 01）中的管标本，这是一项调查18-70岁男性阴茎和阴囊HPV感染的纵向研究。HIM研究从2005年开始招募了巴西、墨西哥和美国的男性，并增加了一项奖励后方案，以收集肛管脱落细胞标本（肛管标本收集和检测未得到R 01 CA 098803 01的资助）。 这项为期2年的自然史研究将分析950名男性的存档生物标本和行为数据。纳入的男性包括两组：所有MSM和存档的肛门样本（n=357）和随机抽取的MSW和存档的肛门样本（n=593）。 我们假设MSM肛门HPV感染持续性比MSW更常见，并且与MSM吸烟相关。为了验证这一假设，我们设计了两个具体目标：1。估计24个月期间MSM和MSW中类型特异性肛门HPV的持续性;和2.确定与肛门HPV持续存在独立相关的因素，包括年龄，性行为，吸烟，并发性传播感染和HPV抗体。 鉴于HIM研究的基础设施和样本量，拟议的研究将有助于产生关于HPV持续性的发现，以解决与肛门癌相关的基本问题。 我们提出的研究将产生第一个强大的估计肛门HPV的持续性在MSM和MSW招募跨国从一般社区。

DESCRIPTION (provided by applicant): Anal cancer is primarily caused by oncogenic human papillomavirus (HPV) types. Persistence of oncogenic HPV infection is the most important early biological event that marks increased risk for development of precancerous anal intraepithelial neoplasia. Annual anal cancer incidence among HIV-negative men having sex with men (MSM) in the US is several fold higher than cervical cancer incidence among women. It is unknown why only some MSM have persistent anal HPV infection and thus increased risk for anal cancer. Such data are especially critical now for two reasons: 1) current HPV vaccines have not been recommended for boys and men, and 2) current vaccines are not licensed for use among men older than 26 years of age. Thus, a fuller understanding of persistent anal HPV infection, is important for the development of anal cancer interventions among MSM. The Moffitt Cancer Center is uniquely positioned for this research as a result of its collection and archiving of anal canal specimens in the Human Papillomavirus in Men Study (HIM Study: NIH R01 CA098803 01), a longitudinal study investigating penile and scrotal HPV infections in men, ages 18-70 years. The HIM Study recruited men in Brazil, Mexico, and the United States beginning in 2005 and also added a post-award protocol to collect anal canal exfoliated cell specimens (anal canal specimen collection and testing was not funded by R01 CA098803 01). The proposed 2-year natural history study will analyze archived biological specimens and behavioral data from 950 men. The men included comprise two groups: all MSM with archived anal specimens (n=357) and a random sample of MSW with archived anal specimens (n=593). We hypothesize that anal HPV infection persistence in MSM is more common than in MSW and is associated with cigarette smoking among MSM. To test the hypothesis, we designed two Specific Aims: 1. Estimate persistence of type-specific anal HPV among MSM and MSW over a 24 month period; and 2. Determine factors independently associated with persistence of anal HPV including age, sexual behavior, cigarette smoking, concurrent sexually transmitted infections, and HPV antibodies. Given the infrastructure and sample size available with the HIM Study, the proposed research is powered to produce findings on HPV persistence that address fundamental questions related to anal cancer. Our proposed research will produce the first robust estimates of anal HPV persistence in MSM and MSW recruited cross-nationally from the general community.