Cutaneous Human Papillomavirus Infection and Risk of Incident External Genital Le

阴茎癌是一种死亡率高、生理和性心理后果严重的疾病。我们的 关于人乳头瘤病毒(HPV)在阴茎癌发生中的作用的认识主要是 来源于对阿尔法属(α-HPV)粘膜HPV类型的研究，阿尔法属是HPV的16个属之一。粘膜 甲型HPV感染约占每年阴茎癌发病率的50%。人们对此知之甚少 HPV类型的多样性参与了阴茎癌前病变的发生。它的意义 在皮肤HPV的贝塔属(β-HPV)，一组HPV普遍存在并持续存在于健康 人类皮肤或其与粘膜α-HPV的联合暴露在阴茎癌变中的作用尚未得到评估。 该项目的目标是对一种新的假设进行前瞻性流行病学调查： 单独或与粘膜α-HPV联合暴露于皮肤β-HPV会增加外源性HPV感染的风险 有可能导致阴茎癌的生殖器病变(EGL)。这项研究的两个具体目标是： (1)评估皮肤β-HPV和粘膜α-HPV暴露的基线流行率，并调查影响因素 与任何β-HPV暴露以及与粘膜α-HPV联合暴露相关；(2)确定 基线暴露于皮肤中的β-HPV，单独或与粘膜中的α-HPV暴露相关联 以及随后的EGL的发展。 我们提出了一个病例队列设计，嵌套在4072个已建立和持续的纵向队列中。 男性(HIM研究)。研究人群将由随机选择的550名男性和所有 发生在父母队列中的急性早幼粒细胞白血病病例(迄今230例)。将对基线血清样本进行检测 多种皮肤β-HPV和粘膜α-HPV型特异性血清抗体作为人类免疫缺陷病毒的标志物 使用高通量多重血清学分析进行HPV暴露。意外事故特惠津贴个案将会从 以活检证实的病理诊断为基础的父母队列是EGL诊断的黄金标准。 这项拟议的项目是第一项评估两种疾病之间的时间相关性的流行病学研究。 皮肤β-HPV感染与潜在恶性EGL的风险。它利用现有的资源 这是一项由美国国立卫生研究院资助的大型研究，是开发可检验假说的一种成本效益策略。这项研究将使 通过早期了解皮肤中β-HPV暴露的流行率，做出了重大贡献 一般男性群体，以及皮肤β-HPV在阴茎癌变中的意义。如果皮肤贝塔- HPV被发现在可能导致阴茎癌的EGL中起病因学作用，我们的发现可以 告知未来与HPV相关的癌症预防策略和疫苗开发，以防止β-HPV感染 以及相关的损害，进而降低阴茎癌的发病率，特别是在处于 风险增加，但缺乏获得当前预防性疫苗的常规途径。

Penile cancer is a disease with a high mortality, serious physical and psychosexual consequences. Our knowledge on the role of Human Papillomavirus (HPV) in penile carcinogenesis has been predominantly derived from studies of mucosal HPV types in the alpha genus (alpha-HPV), one of the 16 genera of HPV. Mucosal alpha-HPV infection is responsible for approximately 50% of annual penile cancer incidence. Little is known about the diversity of HPV types involved in the development of precursor lesions to penile cancer. The significance of cutaneous HPV in the beta-genus (beta-HPV), a group of HPV ubiquitously and persistently present on healthy human skin, or its combined exposures with mucosal alpha-HPV in penile carcinogenesis has not been evaluated. The goal of this project is to conduct a prospective epidemiologic investigation of a new hypothesis: exposures to cutaneous beta-HPV, either individually or jointly with mucosal alpha-HPV, increase the risk of external genital lesions (EGLs) that have malignant potential for penile cancer. The two specific aims of the study are: (1) estimate baseline prevalence of cutaneous beta-HPV and mucosal alpha-HPV exposures, and investigate factors associated with any beta-HPV exposure as well as joint exposures with mucosal alpha-HPV; (2) determine whether baseline exposures to cutaneous beta-HPV, individually or jointly with mucosal alpha-HPV exposures, are associated with subsequent development of EGLs. We propose a case-cohort design nested within an established and ongoing longitudinal cohort of 4072 men (the HIM Study). The study population will consist of a randomly selected sub-cohort of 550 men and all incident EGL cases (n=230 to date) arising from the parent cohort. Baseline serum samples will be tested for type-specific serum antibodies to a wide array of cutaneous beta-HPV and mucosal alpha-HPV types as the marker of HPV exposures using high throughput multiplex serology assays. Incident EGL cases will be enumerated from the parent cohort based on biopsy-confirmed pathologic diagnosis, the gold standard for EGL diagnosis. The proposed project is the first epidemiologic study to evaluate the temporal association between cutaneous beta-HPV infection and risk of EGLs with malignant potential. It utilizes the existing resources of a large NIH-funded study and is a cost-effective strategy to develop testable hypotheses. This study will make a significant contribution by generating early knowledge of the prevalence of cutaneous beta-HPV exposures in the general male community, and the significance of cutaneous beta-HPV in penile carcinogenesis. If cutaneous beta- HPV is found to play an aetiological role in EGLs potentially leading to penile carcinoma, our findings can inform future HPV-related cancer prevention strategies and vaccine development to prevent beta-HPV infection and associated lesions, and in turn reduce penile cancer incidence, especially in older adult men who are at increased risk but lack routine access to the current prophylactic vaccines.