Effect of Male Circumcision on Penile HPV Infection

描述（由申请人提供）：人乳头瘤病毒（HPV）是女性浸润性宫颈癌（ICC）和其他肛门生殖器癌（包括肛门癌、阴茎癌、阴道癌和外阴癌）的主要原因。需要采取公共卫生干预策略，以减少高危HPV类型的生殖器获得，以预防这些影响女性和男性的癌症。鉴于男性在将HPV传播给女性性伴侣方面很重要，减少男性HPV感染和持续性的干预措施可能是一项重要的HPV预防策略，对男性和女性都有好处。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。然而，男性包皮环切术减少HPV阴茎感染获得和/或持续性的证据只能通过前瞻性随机临床试验（RCT）获得。 北卡罗来纳州大学与联合国妇女和男子管理学院合作（伊利诺伊州内罗毕大学和马尼托巴大学生殖健康项目）男性健康诊所、芝加哥伊利诺伊大学、内罗毕大学、纽约市阿尔伯特·爱因斯坦医学院、阿姆斯特丹自由大学医学中心建议研究男性包皮环切术对阴茎HPV感染风险和自然史的影响肯尼亚基苏穆性活跃年轻男子感染。这项关于阴茎HPV感染的研究是在一项正在进行的“母体”RCT中进行的，该RCT旨在评估男性包皮环切术在降低基苏穆18-24岁男性HIV发病率方面的作用，该研究始于2002年2月。 该HPV项目旨在确定目前正在收集的阴茎脱落细胞样本中HPV DNA的类型特异性患病率，作为正在进行的男性包皮环切术RCT的一部分。预计将有2，442名男性从两个解剖部位（阴茎干和龟头/冠状沟）提供阴茎脱落细胞标本。在入组时以及6个月、12个月、18个月和24个月随访访视时采集这些样本。将使用灵敏的PCR检测试剂盒对标本进行检测，以检测各种HPV DNA类型。将使用实时PCR测定HPV 16、18、31、33和45型阳性样本的HPV病毒载量。在最终24个月访视时，将在该正在进行的RCT中增加一项新的临床检查（使用3%乙酸和辅助放大镜进行目视检查），以确定是否存在阴茎病变（即，扁平病变、丘疹性病变、或尖形颈突）。 研究结果将提供迄今为止关于男性包皮环切术对男性HPV感染和阴茎病变影响的最明确证据。如果发现男性包皮环切术在减少HPV感染或男性阴茎病变方面是有效和安全的，那么它可以反过来减少HPV的患病率和女性相关的宫颈肿瘤。

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.