HPV & cervix neoplasia in a large, long-term HIV+ cohort

描述（由申请人提供）：患有艾滋病毒/艾滋病的妇女患宫颈癌的风险很高，并且感染人乳头瘤病毒（HPV）的比率很高，HPV是宫颈癌的病毒原因。通过对2,793名HIV阳性和975名HIV阴性妇女进行半年一次的评估，这些妇女参加了妇女机构间HIV研究（WIHS），这是一个多中心队列，“WIHS HPV调查”旨在成为HIV合并感染对HPV和宫颈发育不良影响的确定性研究。本申请寻求对WIHS继续进行HPV研究的支持。拟议的项目将是第一个系统性研究宿主免疫状态对HIV+女性HPV自然史影响的类型特异性差异的努力。我们最近的研究结果表明，HPV 16型占所有宫颈癌的一半，受任何HPV类型的免疫状态（CD 4+计数）的影响最小。与HPV 16相关的两种HPV类型也与CD 4+弱相关。然而，其他HPV尚未得到充分表征，我们以前也无法解决血浆HIV RNA和CD 4+计数之间的相互作用。WIHS HPV调查的继续将提供所需的统计功效，以通过合并血浆HIV RNA/CD 4+分层检查HPV类型特异性结果，并且它将生成关于HIV+女性HPV感染的唯一真正长期前瞻性数据-在女性可以携带HIV多年的时代有价值的数据。这项应用也是研究当地宫颈HIV水平及其对HPV感染影响的重要机会。众所周知，生殖道中存在大量的HIV区室化，但宫颈HIV RNA水平是否与HPV独立相关，或与血浆水平相比，与HPV的相关性更强，尚未确定。最后，一旦确定感染了致癌HPV，免疫状态在严重宫颈不典型增生的进展中起什么作用仍不清楚。WIHS的持续随访将首次使人们有可能前瞻性地研究艾滋病毒阳性妇女严重宫颈发育不良（一种真正的癌症前兆）的风险因素。总之，目的是研究：（i）宿主免疫状态对HPV自然史影响的类型特异性差异;（ii）宫颈HIV RNA水平与HPV感染之间的关系;（iii）HIV+妇女进展为严重宫颈发育不良的风险因素。

DESCRIPTION (provided by applicant): Women with HIV/AIDS are at high risk of cervical cancer, and have high rates of infection with human papillomavirus (HPV), the viral cause of cervical cancer. Through the semiannual evaluation of 2,793 HIV+and 975 HIV- women enrolled in the Women's Interagency HIV Study (WIHS), a multicenter cohort, the "WIHS HPV Investigation" is intended to be the definitive study of the effects of HIV coinfection on HPV and cervical dysplasia. This application seeks support for continuation of HPV research in the WIHS. The proposed project will be the first systematic effort to study type-specific differences in the effects of host immune status on HPV natural history in HIV+ women. Our recent results showed that HPV 16, the type that accounts for half of all cervical cancers, was the least affected by immune status (CD4+ count) of any HPV type. Two HPV types related to HPV 16 were also weakly associated with CD4+. Other HPVs, however, have not been adequately characterized, nor could we previously address the strong interaction between the effects of plasma HIV RNA and CD4+ count. Continuation of the WIHS HPV Investigation will provide the needed statistical power to examine HPV type-specific results by combined plasma HIV RNA/CD4+ strata, and it will generate the only truly long term prospective data regarding HPV infection in HIV+ women -valuable data in an era in which women can live for years with HIV. This application also represents an important opportunity to study local cervical HIV levels and their effects on HPV infection. It is known that there is substantial compartmentalization of HIV in the genital tract, but whether cervical HIV RNA levels are independently or, compared with plasma levels, more strongly associated with HPV has not been determined. Finally, once infection with an oncogenic HPV is established it remains unclear what role immune status plays in progression to severe cervical dysplasia. Continued follow-up in the WIHS will, for the first time, make it possible to prospectively study the risk factors for severe cervical dysplasia (a true cancer precursor) in HIV+ women. In summary, the aims are to study: (i) type-specific differences in the effects of host immune status on HPV natural history; (ii) the relationship between cervical HIV RNA levels and HPV infection; (iii) risk factors for progression to severe cervical dysplasia in HIV+ women.