Effect of Male Circumcision on Penile HPV Infection

描述(申请人提供)：人乳头瘤病毒(HPV)是女性浸润性宫颈癌(ICC)以及其他肛门生殖道癌的主要原因，包括肛门癌、阴道癌、阴道癌和外阴癌。需要公共卫生干预战略，以减少生殖器获得高危HPV类型，以预防这些影响女性和男性的癌症。鉴于男性在将HPV传播给其女性性伴侣方面很重要，减少男性感染HPV和持续感染HPV的干预措施可能是一项重要的HPV预防战略，对男性和女性都有利。有限的横断面数据表明，男性包皮环切术可能会减少阴茎HPV感染的携带者。然而，男性包皮环切术减少HPV阴茎感染获得性和/或持久性的证据只能通过进行前瞻性随机临床试验(RCT)来获得。 北卡罗来纳大学与UniM(内罗毕大学、伊利诺伊大学和马尼托巴省生殖健康项目)男性健康诊所、伊利诺伊大学芝加哥分校、内罗毕大学、纽约市阿尔伯特·爱因斯坦医学院和阿姆斯特丹Vrije大学医学中心合作，提议研究男性割礼对肯尼亚基苏木年轻性行为活跃男性阴茎HPV感染风险和自然病史的影响。这项拟议的关于阴茎HPV感染的研究嵌套在正在进行的“父母”随机对照试验中，以评估男性包皮环切术在降低基苏木18-24岁男性艾滋病毒发病率方面的效果，该研究始于2002年2月。 这一HPV项目建议确定阴茎脱落细胞样本中特定类型的HPV DNA流行率，作为正在进行的男性包皮环切术随机对照试验的一部分。据估计，将有2442名男性捐献两个解剖部位(阴茎和龟头/冠沟)的阴茎脱落细胞标本。这些样本是在登记时以及6、12、18和24个月的随访中收集的。将使用灵敏的聚合酶链式反应检测样本，以检测各种HPVDNA类型。HPV16、18、31、33和45型阳性样本的HPV病毒载量将使用实时聚合酶链式反应进行检测。一项新的临床检查(用3%醋酸和辅助放大)将在最后24个月的最后一次随访时加入正在进行的RCT，以确定是否存在阴茎病变(即扁平病变、丘疹病变或尖锐湿疣)。 研究结果将为男性包皮环切术对男性HPV感染和阴茎损伤的影响提供迄今为止最确凿的证据。如果男性包皮环切术在减少男性HPV感染或阴茎病变方面被发现是有效和安全的，那么它反过来可以降低女性HPV的患病率和相关的宫颈肿瘤。

DESCRIPTION (provided by applicant): Human papillomavirus (HPV) is the central cause of invasive cervical cancer (ICC) in women, and other anogenital cancers, including anal, penile, vaginal and vulvar cancers. Public health intervention strategies are needed to reduce the genital acquisition of high-risk HPV types to prevent these cancers that affect women and men. Given that men are important in transmitting HPV to their female sexual partners, interventions that reduce HPV acquisition and persistence in men could be an important HPV prevention strategy benefiting both men and women. Limited cross-sectional data suggest that male circumcision may reduce the carriage of penile HPV infection. However, proof that male circumcision reduces HPV penile infection acquisition and/or persistence can only be obtained through the conduct of a prospective, randomized clinical trial (RCT). The University of North Carolina, in collaboration with the UNIM (Universities of Nairobi, Illinois and Manitoba Reproductive Health Project) Male Health Clinic, The University of Illinois at Chicago, the University of Nairobi, the Albert Einstein College of Medicine in New York City, and the Vrije Universiteit Medical Center in Amsterdam proposes to study of the effect of male circumcision on the risk and natural history of penile HPV infection in young, sexually active men in Kisumu, Kenya. This proposed study of penile HPV infection is nested within an ongoing "parent" RCT to assess the effect of male circumcision in reducing HIV incidence in 18-24 year-old men in Kisumu that began in February 2002. This HPV project proposes to determine the type-specific HPV DNA prevalence in penile exfoliated cell samples currently being collected as part of the ongoing RCT of male circumcision. An estimated 2,442 men are expected to contribute penile exfoliated cell specimens from two anatomical sites (the shaft and glans/coronal sulcus). These sample are being collected at enrollment and at the 6-, 12-, 18- and 24- month follow-up visits. Specimens will be tested using a sensitive PCR assay to detect a wide-range of HPV DNA types. HPV viral load of samples positive for HPV types 16, 18, 31, 33 and 45 will be determined using a real-time PCR. A new clinical examination (a visual inspection with 3% acetic acid and aided magnification) will be added to this ongoing RCT at the final 24-month visit to determine the presence of penile lesions (i.e., flat lesions, papular lesions, or condolymata acuminate). Study results will provide the most definitive evidence to date regarding the effect of male circumcision on HPV infection and penile lesions in men. If male circumcision is found to be effective and safe in reducing HPV infection or penile lesions in men, it could in turn reduce HPV prevalence and associated cervical neoplasia in women.