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

感染艾滋病毒/艾滋病的妇女患宫颈癌的风险很高，感染人乳头瘤病毒（HPV）的比例也很高，HPV是导致宫颈癌的病毒。通过对参加妇女跨机构艾滋病毒研究（WIHS）的2,793名艾滋病毒阳性和975名艾滋病毒阳性妇女进行半年一次的评估，这是一个多中心队列，“WIHS HPV调查”旨在成为艾滋病毒合并感染对HPV和宫颈发育不良影响的决定性研究。本申请寻求支持在WIHS中继续进行HPV研究。该项目将是第一个系统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项目。我们最近的研究结果表明，占所有宫颈癌一半的HPV 16型受免疫状态（CD4+计数）的影响最小。与HPV 16相关的两种HPV类型也与CD4+弱相关。然而，其他hpv没有得到充分的表征，我们以前也无法解决血浆HIV RNA和CD4+计数之间的强相互作用。继续进行WIHS HPV调查将提供必要的统计力量，通过联合血浆HIV RNA/CD4+分层来检查HPV类型特异性结果，并将产生关于HIV+妇女中HPV感染的唯一真正长期前瞻性数据-在一个妇女可以携带HIV多年的时代，这是有价值的数据。这个应用程序也代表了一个重要的机会来研究当地宫颈HIV水平及其对HPV感染的影响。众所周知，HIV在生殖道中存在大量的区隔性，但宫颈HIV RNA水平是独立的，还是与血浆水平相比，与HPV的相关性更强，目前还没有确定。最后，一旦感染了致瘤性HPV，免疫状态在严重宫颈发育不良的进展中所起的作用仍不清楚。在WIHS中继续进行随访，将首次使前瞻性研究HIV阳性妇女严重宫颈发育不良（真正的癌症前兆）的危险因素成为可能。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）宫颈爱滋病病毒RNA水平与人乳头瘤病毒感染的关系；（iii）艾滋病毒阳性妇女发展为严重宫颈发育不良的危险因素。

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.