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）发展的中心病因。艾滋病毒阳性妇女感染HPV和宫颈疾病的风险大大增加，这种风险随着CD4+ t细胞减少和/或艾滋病毒RNA水平升高而增加。然而，令人惊讶的是，很少有研究评估了艾滋病毒阳性妇女感染HPV的自然史。我们的知识差距包括艾滋病毒阳性妇女中HPV DNA的持久性及其与宫颈肿瘤风险的关系。潜在HPV感染的重新激活被认为对免疫受损的个体很重要，但缺乏明确的证据表明这种情况会发生。高活性抗逆转录病毒治疗（HAART）对HPV自然史的影响尚不清楚。本应用程序的目的是研究艾滋病毒对HPV感染的自然史和宫颈肿瘤发展的长期影响，使用从妇女机构间艾滋病毒研究（WIHS）获得的标本。WIHS队列是一个庞大的，地理和种族多样化的艾滋病毒阳性人群（n=2056）和风险匹配的艾滋病毒阴性妇女（n=569）。自入组以来（1994年10月至1995年11月），每隔6个月对WIHS受试者进行随访，随访资金一直持续到2002年。我们分析了入组时的HPV和细胞学结果，但大多数计划就诊（随访2- 7年）尚未安排HPV DNA检测。根据这项申请，我们会对所有未检测的宫颈样本进行HPV DNA测试，而对HPV 16、18和/或31阳性的样本进行进一步测试，以确定特定类型的变异。将测量对乳头瘤病毒抗原的血清抗体，包括一组病毒样颗粒。我们的具体目的包括：(1)研究HIV血清状态、CD4+ t细胞、HIV RNA水平和HAART使用与3个结局风险的关系，即：特定类型HPV DNA检测的发生率、HPV DNA的持久性和宫颈癌的发生率；(2)确定HPV是否可以潜伏并重新激活；(3)研究hiv阳性和阴性女性对HPV的体液免疫反应及其与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.