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

携带艾滋病毒/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是导致宫颈癌的病毒原因。通过对参加妇女机构间艾滋病毒研究(WIHS)的2793名HIV+和975名艾滋病毒妇女进行半年一次的评估，WIHS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权威研究。本申请旨在为WIHS中HPV研究的继续提供支持。这项拟议的项目将是第一次系统地研究宿主免疫状态对HIV+妇女HPV自然病史的影响的特定类型的差异。我们最近的结果表明，占所有宫颈癌一半的HPV16型受到任何HPV型中免疫状态(CD4+计数)的影响最小。与HPV16相关的两种HPV类型与CD4+的相关性也很弱。然而，其他HPV还没有得到充分的表征，我们以前也不能解决血浆HIV RNA和CD4+计数之间的强烈相互作用。WIHS HPV调查的继续将提供所需的统计力量，通过结合血浆HIV RNA/CD4+层析来检查HPV特定类型的结果，并将产生关于HIV+妇女中HPV感染的唯一真正长期的前瞻性数据--在一个妇女可以携带艾滋病毒多年的时代，这是有价值的数据。这一应用也为研究当地宫颈艾滋病毒水平及其对HPV感染的影响提供了一个重要机会。众所周知，生殖道中的艾滋病毒有很大的区隔，但尚未确定宫颈艾滋病毒RNA水平是独立的，还是与血浆水平相比与HPV有更强的相关性。最后，一旦确定感染致癌性HPV，目前尚不清楚免疫状态在进展为严重的宫颈发育不良中起什么作用。WIHS的持续跟踪将首次使前瞻性地研究HIV+女性严重宫颈发育不良(真正的癌症先兆)的风险因素成为可能。综上所述，这些研究的目的是研究：(I)宿主免疫状态对HPV自然病史的影响的特定类型的差异；(Ii)宫颈HIV RNA水平与HPV感染之间的关系；(Iii)在HIV阳性妇女中进展为严重宫颈不典型增生的危险因素。

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.