HPV & CERVIX NEOPLASIA IN A LARGE, LONG TERM HIV+ COHORT

人乳头瘤病毒（HPV）是大多数宫颈肿瘤（包括浸润性宫颈癌）发生的主要病原体。 HIV阳性的妇女感染HPV和宫颈疾病的风险大大增加，这种风险随着CD 4 + T细胞减少和/或HIV RNA水平升高而增加。 然而，令人惊讶的是，很少有研究评估了HIV阳性女性HPV感染的自然史。 我们的知识差距包括HPV DNA在HIV阳性妇女中的持续存在及其与宫颈肿瘤风险的关系。潜伏性HPV感染的重新激活在免疫受损的个体中很重要，但缺乏明确的证据表明这种情况发生。 高效抗逆转录病毒疗法（HAART）对HPV自然史的影响尚不清楚.本申请的目的是研究HIV对HPV感染自然史和宫颈肿瘤发展的长期影响，使用从妇女机构间HIV研究（WIHS）获得的标本。 WIHS队列是一个庞大的、地理和种族多样化的HIV阳性（n=2056）和风险匹配的HIV阴性女性（n=569）人群。自入组以来（1994年10月至1995年11月），WIHS受试者每隔6个月接受一次随访，并资助随访至2002年。 我们在入组时分析了HPV和细胞学结果，但尚未安排大多数计划访视（随访2- 7年）的HPV DNA检测。 根据这项申请，我们将对所有未经检测的宫颈标本进行HPV DNA检测，并对HPV 16、18和/或31阳性的标本进行进一步检测，以确定类型特异性变体。 将测量乳头瘤病毒抗原的血清抗体，包括一组病毒样颗粒。 我们的具体目标包括：（1）研究HIV血清学状态、CD 4 + T细胞、HIV RNA水平和HAART使用与3种结局风险的关系，即特异性HPV DNA检测、HPV DNA持续存在和宫颈肿瘤发生：（2）确定HPV是否可以潜伏然后再激活;（3）研究HIV阳性和阴性妇女对HPV的体液免疫应答及其与HPV自然史的关系。

Human papillomavirus (HPV) is the central etiologic agent in the development of most cervical neoplasms, including invasive cervical cancer. HIV-positive women are at substantially elevated risk for HPV infection as well as cervical disease, and this risk increases with diminished CD4+ T-cell and/or higher HIV RNA levels. Surprisingly few studies, however, have assessed the natural history of HPV infection in HIV-positive women. Gaps in our knowledge include the persistence of HPV DNA in HIV-positive women and its relation with risk of cervical neoplasms. Reactivation of latent HPV infections has been suggested to be important in immune compromised individuals, but clear evidence that this occurs is lacking. The effects of highly active anti- retroviral therapy (HAART) on HPV natural history are unknown. The purpose of this application is to study the long term effects of HIV on the natural history of HPV infection and the development of cervical neoplasms, using specimens obtained from the Women's Interagency HIV Study (WIHS). The WIHS cohort is a large, geographically and ethnically diverse population of HIV- positive (n=2056), and risk-matched HIV-negative women (n=569). Since enrollment (October, 1994 - November 1995) WIHS subjects have been followed at 6 month intervals, and follow-up is funded through 2002. We have analyzed HPV and cytologic results at enrollment, but HPV DNA testing for most planned visits (years 2- 7 of follow-up) has not been arranged. Under this application we will test all untested cervical specimens for HPV DNA, and specimens positive for HPV 16, 18 and/or 31 will be further tested to identify the type-specific variant. Serum antibodies to papillomavirus antigens, including a panel of virus-like particles, will be measured. Our specific aims include: (1) To study the relation of HIV serostatus, CD4+ T-cell, HIV RNA levels, and use of HAART with risk of 3 outcomes, namely, incident type-specific HPV DNA detection, persistence of HPV DNA, and incident cervical neoplasms; (2) To determine whether HPV can become latent and then be reactivated; and (3) To study humoral immune responses to HPV and their relation with HPV natural history in HIV-positive and -negative women.