Natural History of HPV Infection in Men: The HIM Study

描述(由申请人提供)： 人乳头瘤病毒(HPV)是一种性传播感染，与女性的浸润性宫颈癌、外阴和肛门癌以及男性的阴茎和肛门癌密切相关。在国际上，宫颈癌的发病率差异很大，墨西哥的发病率很高，美国和欧洲的发病率很低。在美国，与非西班牙裔白人相比，西班牙裔女性的发病率显著上升。在预测HPV感染和宫颈疾病的风险方面，男性伴侣的性行为可能与西班牙裔或墨西哥女性的个人性行为一样重要，甚至更重要。不幸的是，关于男性HPV感染的流行率、发病率和清除情况知之甚少，这阻碍了控制男性和女性感染的努力。我们建议对男性进行一项大型的两国(美国-墨西哥)前瞻性研究，即男性中的HPV研究(HIM)。这一修订申请的目的是加深我们对男性HPV感染自然病史的了解，以便开发有效的计划来减轻男性和女性的HPV疾病负担。具体地说，我们的目标是招募3000名男性，他们将在四年内每六个月接受一次检查，确定特定类型阴茎HPV感染的发生率和持久性，对HPV感染的体液免疫反应，并评估与男性特定类型HPV感染的获得、持续和清除独立相关的因素。我们假设HPV感染类型在男性中的分布因国家不同而不同，男性中的大多数感染是一过性的，并且类型特异性HPV抗体反应只在持续阳性的男性中发生。此外，我们假设，目前使用避孕套和包皮环切术可以降低发生HPV感染的风险，而其他性感染会增加风险。我们提出的研究是独一无二的，因为它将前瞻性地评估美国和墨西哥的一大群男性中的HPV感染，这两个国家代表着高风险和低风险国家。这项研究是及时的，因为它将提供关于男性感染类型和感染发生率的信息，这是设计男性疫苗效力研究所必需的。它具有成本效益，在墨西哥运营，与美国相比，每个参与者的注册成本显著降低，招募具有两国代表性的男性，并与业界合作，大幅降低HPV基因分型成本。

DESCRIPTION (provided by applicant): Human papillomavirus (HPV), a sexually transmitted infection, is strongly associated with invasive cervical, vulvar, and anal cancers in women, and penile and anal cancers in men. Internationally, the incidence of cervical cancer varies greatly, with high rates observed in Mexico and low rates observed in the US and Europe. In the US, Hispanic women have significantly elevated rates of disease compared with non-Hispanic whites. The sexual behavior of the male partner may be as or more important than a Hispanic or Mexican woman's personal sexual behavior in predicting her risk of HPV infection and cervical disease. Unfortunately, little is known regarding the prevalence, incidence, and clearance of HPV infections in men, hampering efforts to control infection in both men and women. We propose to conduct a large binational (US-Mexico) prospective study of men, the HPV in Men Study (HIM). The goal of this revised application is to further our understanding of the natural history of HPV infection in men so that effective programs can be developed to reduce HPV disease burden in both men and women. Specifically, our aims are to enroll a cohort of 3000 men who will be examined every six months for four years, determine the incidence and persistence of type-specific penile HPV infections, the humoral immune response to HPV infection, and assess the factors independently associated with acquisition, persistence, and clearance of type-specific HPV infections in men. We hypothesize that HPV infection type distribution in men differs by country, that most infections in men are transient, and that type-specific HPV antibody response occurs only among persistently positive men. In addition, we hypothesize that current condom use and circumcision confers reduced risk of incident HPV infection, and that other sexually acquired infections increase risk. Our proposed study is unique in that it will prospectively assess HPV infection in a large cohort of men in the US and Mexico, representing countries of high and low risk. The study is timely in that it will yield information on types of male infection and incidence of infection necessary to design vaccine efficacy studies in men. It is cost-effective, operating in Mexico with a significantly reduced cost per participant enrolled compared to the US, enrolling men representative of both countries, and partnering with industry to significantly reduce HPV genotyping costs.