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

对感染艾滋病毒的女性进行肛门癌前体筛查的有效性

• 批准号: 8210228
• 负责人: Elizabeth Chiao
• 金额: $ 63.71万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-19 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8210228
• 关键词: Accounting; Address; Anal Intraepithelial Neoplasia; Anal carcinoma; Anus; Behavioral; Biological Assay; Biopsy; CD4 Lymphocyte Count; Cancerous; Cause of Death; Cervical; Cervical Cancer Screening; Characteristics; Cohort Studies; Cost-Benefit Analysis; Cytology; Data; Detection; Economics; Effectiveness; Epidemiologic Studies; Epidemiology; Epithelial; General Population; Gold; Guidelines; HIV; HPV-High Risk; Healthcare; High Prevalence; Highly Active Antiretroviral Therapy; Histology; Human Papillomavirus; Human papilloma virus infection; Hybrids; Immunologics; Incidence; Individual; Intraepithelial Neoplasia; Lesion; Life; Longitudinal Studies; Malignant Neoplasms; Malignant Squamous Cell Neoplasm; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Messenger RNA; Methods; Morbidity - disease rate; Natural History; Neoplasms; New York; Opportunistic Infections; Participant; Persons; Policy Making; Population Study; Premalignant; Prevalence; Primary Health Care; Publishing; Quality of life; Recommendation; Recording of previous events; Reporting; Research; Resolution; Resources; Risk; Risk Factors; Sampling; Screening procedure; Sensitivity and Specificity; Site; Specificity; Testing; Time; Triage; Visit; Vulva; Woman; antiretroviral therapy; cancer prevention; clinical decision-making; cohort; condyloma; cost effective; economic evaluation; economic impact; high risk; high standard; improved; men; mortality; multidisciplinary; therapy adherence

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. PUBLIC HEALTH RELEVANCE: 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 anal intraepithelial neoplasia and is strongly associated with human papillomavirus (HPV) infection. This longitudinal study will provide the necessary information to make policy guidelines for screening for anal cancer in HIV-infected women as well as better characterizing the progression of HPV infection and high-grade anal intraepithelial neoplasia in HIV-infected women in the HAART era.

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），但感染艾滋病毒的妇女患肛门癌的风险至少是普通人群的14倍。与子宫颈癌一样，肛门癌的发生也有高级别上皮内瘤变，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，肛门癌前病变的发生率高达10%。由于艾滋病毒感染妇女中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建议，对宫颈或外阴组织学异常或有肛门生殖器尖锐湿疣史的艾滋病毒感染妇女每年进行肛门细胞学检查。然而，很少或没有证据存在，以确定肛门上皮内瘤变（AIN）在艾滋病毒感染的妇女背景下的最佳筛查策略。在HAART时代，没有对感染hiv的妇女进行高分辨率肛门镜检查（HRA）和定向活检的研究，同时对所有参与者进行肛门细胞学和HPV检测。因此，高级别肛门上皮内瘤变（HGAIN）的患病率尚不清楚，发生这种病变的危险因素也不清楚。HPV检测已被证明是宫颈癌细胞学筛查的有用辅助手段，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有益。因此，我们的具体目的是：具体目的1a：确定艾滋病毒感染妇女首次研究访问时肛门细胞学检查的敏感性（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测定（APTIMA））进行肛门高危HPV检测是否会改善常规肛门细胞学检测的筛查试验特征。具体目标2：确定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变化，具体目标3：对艾滋病毒感染妇女的不同肛门细胞学检查策略进行经济评估。为了实现这些目标，我们提出了一项两点、多学科的研究，利用从300名艾滋病毒感染妇女的2年纵向队列研究中收集的数据，这些妇女将每6个月进行一次评估。这项队列研究将首次提供关于肛门HPV感染和HGAIN的测试特征、流行病学和自然史的重要信息，这些信息是在接受常规肛门细胞学检查的hiv感染妇女队列中进行的。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。