The Effectiveness of Screening HIV-Infected Women for Anal Cancer Precursors

描述（由申请人提供）：尽管广泛使用高效抗逆转录病毒疗法（HAART），但与普通人群相比，HIV感染女性发生肛门癌的风险至少是普通人群的14倍。与宫颈癌一样，肛门癌出现在高级别上皮内瘤变之前，并与人乳头瘤病毒（HPV）感染密切相关。在感染艾滋病毒的妇女中，肛门癌前病变的发病率高达10%。由于感染艾滋病毒的妇女肛门癌前病变和癌性病变的惊人增加，人们越来越重视肛门癌的预防，包括2007年纽约州艾滋病毒初级保健指南中的建议，即对有异常宫颈或外阴组织学史或肛门生殖器湿疣史的感染艾滋病毒的妇女进行年度肛门细胞学检测。然而，几乎没有证据可以确定HIV感染妇女肛门上皮内瘤变（AIN）的最佳筛查策略。在HAART时代，还没有对HIV感染妇女进行高分辨率肛门镜检查（HRA）和直接活检的研究，所有参与者同时进行肛门细胞学和HPV检测。因此，尚不清楚高级肛门上皮内瘤变（HGAIN）的患病率，也不清楚发生这种病变的危险因素。HPV检测已被证明是一个有用的辅助宫颈细胞学宫颈癌筛查，但是，我们不知道如果使用HPV分流艾滋病毒感染的女性异常肛门细胞学将是有益的。因此，我们的具体目标是：具体目标1a：在HIV感染女性中确定初次研究访视时肛门细胞学检测的灵敏度（通过使用HRA引导的肛门活检确认细胞学异常）和特异性（通过HRA确认正常细胞学）。具体目标1b：确定使用不同的HPV检测方法（包括HPV杂交捕获2（HC 2）和HPV mRNA检测（APTIMA））进行肛门高危（HR）HPV检测是否会改善单独进行常规肛门细胞学检测的筛查检测特征。具体目标二：确定基线患病率和与HGAIN和肛门HPV相关的危险因素;量化接受常规肛门细胞学检测的HIV感染妇女的HGAIN和肛门HPV发病率以及患病率随时间的变化;具体目标3：对HIV感染妇女的不同肛门细胞学检测策略进行经济评估。为了解决这些问题，我们提出了一个两个网站，多学科研究，利用收集的数据从一个为期2年的纵向队列研究的300名艾滋病毒感染的妇女将在6个月的时间间隔进行评估。这项队列研究将是第一个提供重要信息的测试特点，流行病学，和肛门HPV感染和HGAIN的一个队列中接受常规肛门细胞学检测的HIV感染的妇女的自然史。然后，这些数据将用于进行全面的成本效益分析，这将指导临床决策，为这些妇女提供最佳的肛门癌筛查方法。

DESCRIPTION (provided by applicant): HIV-infected women have at least fourteen times the risk of developing anal carcinoma compared with the general population despite the widespread use of highly active antiretroviral therapy (HAART). Like cervical cancer, anal cancer appears to be preceded by high-grade intraepithelial neoplasia and is strongly associated with human papillomavirus (HPV) infection. The prevalence of anal precancerous lesions among HIV-infected women has been shown to be as high as 10%. Due to this alarming increase in anal precancerous and cancerous lesions among HIV-infected women, there has been an increasing emphasis on anal cancer prevention, including recommendations in the 2007 New York state HIV primary care guidelines to perform annual anal cytology testing among HIV-infected women with a history of abnormal cervical or vulvar histology or history of anogenital condyloma. However, little to no evidence exists to define the optimal screening strategy for anal intraepithelial neoplasia (AIN) in the context of HIV-infected women. In the HAART era, there have been no studies of HIV-infected women in which high resolution anoscopy (HRA) with directed biopsy was performed on all participants with concurrent sampling for anal cytology and HPV testing. Therefore the prevalence of high-grade anal intraepithelial neoplasia (HGAIN) is not known, nor are the risk factors for developing this lesion. HPV testing has been shown to be a useful adjunct to cervical cytology for cervical cancer screening , however, we do not know if using HPV to triage HIV-infected women with abnormal anal cytology would be of benefit. Therefore, our specific aims are: Specific aim 1a: to determine the sensitivity (through confirmation of cytological abnormalities using HRA-guided anal biopsies) and specificity (through HRA confirmation of normal cytology) of anal cytology testing at the initial study visit among HIV-infected women. Specific aim 1b: to determine if anal high risk (HR) HPV testing using different methods of HPV detection, including HPV Hybrid Capture 2 (HC2) and HPV mRNA assays (APTIMA), will improve the screening test characteristics of routine anal cytology testing alone. Specific Aim 2: to determine the baseline prevalence rate, and risk factors associated with HGAIN and anal HPV; and to quantify HGAIN and anal HPV incidence, and prevalence rate changes over time among HIV-infected women undergoing routine anal cytologic testing, and specific Aim 3: to perform an economic evaluation of different anal cytology testing strategies among HIV-infected women. In order to address these aims, we propose a two-site, multidisciplinary study, utilizing data collected from a 2-year longitudinal cohort study of 300 HIV-infected women who will be evaluated at 6 month intervals. This cohort study will be the first to provide important information regarding the test characteristics, epidemiology, and natural history of anal HPV infection and HGAIN among a cohort of HIV-infected women undergoing routine anal cytology testing. The data will then be utilized to perform comprehensive cost-benefit analyses, which will direct clinical decision making on an optimal anal cancer screening approach for these women.