Factors associated with persistent anal human papillomavirus infection among men

描述(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。持续的致癌性HPV感染是最重要的早期生物学事件，标志着癌前病变发生的风险增加。在美国，HIV阴性男男性行为者(MSM)每年的肛门癌发病率是女性宫颈癌发病率的几倍。目前尚不清楚为什么只有一些男男性接触者持续感染HPV，从而增加了患肛门癌的风险。这些数据现在尤其重要，原因有两个：1)目前的HPV疫苗没有被推荐给男孩和男性，2)目前的疫苗没有获得在26岁以上的男性中使用的许可。因此，对持续性肛门HPV感染有更全面的了解，对于男男性接触者的肛门癌干预措施的发展是重要的。莫菲特癌症中心在这项研究中具有独特的地位，因为它收集和归档了肛门 男性人乳头瘤病毒研究(HIM研究：NIH R01 CA098803 01)中的管道标本，这是一项纵向研究，调查18-70岁男性阴茎和阴囊HPV感染。HIM研究从2005年开始在巴西、墨西哥和美国招募男性，并增加了获奖后收集肛管脱落细胞样本的方案(肛管样本收集和检测不是由R01CA098803 01资助的)。这项拟议的为期两年的自然历史研究将分析950名男性的存档生物样本和行为数据。纳入的男性包括两组：所有MSM都有存档的肛门标本(n=357)，以及随机抽取的MSW存档的肛门标本(n=593)。我们假设男男性接触者的肛门HPV感染持久性比MSW中的更常见，并且与MSM中吸烟有关。为了验证这一假设，我们设计了两个具体的目标：1.评估MSM和MSW中特定类型的肛门HPV在24个月期间的持久性；2.确定与肛门HPV持久性独立相关的因素，包括年龄、性行为、吸烟、并发的性传播感染和HPV抗体。鉴于HIM研究的基础设施和样本量，拟议的研究是为了产生关于HPV持久性的发现，解决与肛门癌相关的基本问题。我们建议的研究将产生第一个可靠的估计肛门HPV持久性的男男性接触者和MSW跨国招募的一般社区。

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.