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)，但艾滋病毒感染妇女患肛门癌的风险至少是普通人群的14倍。与宫颈癌一样，肛门癌似乎发生在高度上皮内瘤变之前，并与人类乳头瘤病毒(HPV)感染密切相关。在感染艾滋病毒的妇女中，肛门癌前病变的患病率已被证明高达10%。由于艾滋病毒感染妇女的肛门癌前病变和癌病变的增加令人震惊，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建议对有异常宫颈或外阴组织学病史或肛门生殖器尖锐湿疣病史的艾滋病毒感染妇女进行年度肛门细胞学检查。然而，在感染艾滋病毒的妇女中，几乎没有证据来确定肛门上皮内瘤变(AIN)的最佳筛查策略。在HAART时代，还没有关于HIV感染妇女的研究，在这些研究中，所有参与者都接受了高分辨率肛门镜(HRA)和定向活检，同时进行了肛门细胞学和HPV检测。因此，高级别肛门上皮内瘤变(HGAIN)的流行情况尚不清楚，也不是发生这种病变的危险因素。HPV检测已被证明是宫颈细胞学的一种有用的辅助手段，用于宫颈癌筛查，然而，我们不知道使用HPV对肛门细胞学异常的HIV感染妇女进行分类是否会有好处。因此，我们的具体目标是：具体目标1a：在HIV感染妇女的首次研究访问中，确定肛门细胞学检测的敏感性(通过HRA引导的肛门活检证实细胞学异常)和特异性(通过HRA证实细胞学正常)。具体目的1b：确定使用不同的HPV检测方法，包括HPV杂交捕获2(HC2)和HPV mRNA检测(APTIMA)检测肛门高危(HR)HPV是否会改善单独进行常规肛门细胞学检测的筛查试验特性。具体目标2：确定与HGAIN和肛门HPV相关的基线患病率和危险因素；量化HGAIN和肛门HPV发病率，以及接受常规肛门细胞学检查的艾滋病毒感染妇女的患病率随时间的变化；具体目标3：对艾滋病毒感染妇女不同的肛门细胞学检测策略进行经济评估。为了达到这些目标，我们提出了一项两点多学科研究，利用从300名感染艾滋病毒的妇女进行的为期两年的纵向队列研究中收集的数据，这些妇女将每隔6个月接受一次评估。这项队列研究将首次提供有关接受常规肛门细胞学检查的HIV感染妇女队列中的HPV感染和HGAIN的测试特征、流行病学和自然病史的重要信息。然后，这些数据将被用于进行全面的成本效益分析，这将指导临床对这些女性的最佳肛门癌筛查方法的决策。

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.