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

人乳头瘤病毒(HPV)是包括浸润性宫颈癌在内的大多数宫颈肿瘤发生的主要病原体。艾滋病毒阳性妇女感染HPV和宫颈疾病的风险大大增加，而且这种风险随着CD4+T细胞减少和/或艾滋病毒RNA水平的升高而增加。然而，令人惊讶的是，很少有研究评估艾滋病毒阳性妇女HPV感染的自然病史。我们的知识空白包括艾滋病毒阳性妇女中HPV DNA的持续存在及其与宫颈肿瘤风险的关系。潜伏的HPV感染的重新激活对免疫受损的人来说很重要，但缺乏明确的证据表明这种情况会发生。高效抗逆转录病毒疗法(HAART)对HPV自然病程的影响尚不清楚。这项应用的目的是利用从妇女机构间艾滋病毒研究(WIHS)获得的标本，研究艾滋病毒对HPV感染的自然历史和宫颈肿瘤发展的长期影响。WIHS队列是一大群地理和种族多样化的艾滋病毒阳性(n=2056)和风险匹配的艾滋病毒阴性妇女(n=569)。自注册以来(1994年10月至1995年11月)，WIHS受试者每隔6个月进行一次跟踪，跟踪资金将持续到2002年。我们已经分析了登记时的HPV和细胞学结果，但大多数计划中的就诊(2-7年随访)的HPV DNA检测尚未安排。根据这项申请，我们将检测所有未检测的宫颈样本中的HPVDNA，并将进一步检测HPV16、18和/或31阳性的样本，以确定特定类型的变异。将测量针对乳头状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血清状况、CD4+T细胞、HIV RNA水平和HAART的使用与三种结果风险的关系，即特定类型的HPVDNA检测、HPVDNA的持续存在和子宫颈癌的发生；(2)确定HPV是否可以潜伏并重新激活；(3)研究HIV阳性和阴性妇女对HPV的体液免疫反应及其与HPV自然病史的关系。

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.