Optimizing Age-based Anal Cancer Screening Among People Living with HIV using Decision Analytic Modeling

项目摘要/摘要 肛门癌是第二种最常见的非艾滋病定义的癌症，也是 美国境内的艾滋病毒感染者(HIV+)。肛门癌的发病率随着年龄的增长而增加。使用 近50%的艾滋病毒携带者现在是50岁或以上，筛查形式的预防性医疗保健是一种 主要的公共卫生优先事项，以降低他们患肛门癌的风险。因为从生物学角度讲，肛门癌 与宫颈癌类似，目前的指南(从宫颈癌文献中推断)建议进行筛查 HIV阳性的男性和女性使用肛门细胞学检测高度鳞状上皮内病变( 肛门癌先兆)；然而，最佳筛查方案(开始和停止筛查的年龄以及 用于预防肛门癌的最佳筛查频率)仍然未知。由于缺乏明确的 了解筛查的危害和好处，只有11%的HIV+患者进行了肛门细胞学检查 前一年，导致50%的诊断发生在III期或更差，当5年存活率为 不到40%。 拟议研究的目标是确定合适的候选人进行筛查并确定年龄- 降低HIV+男性和女性肛门癌发病率和死亡率的特定筛查算法。我们 将把来自两个大型临床试验和几个大型数据库的证据整合到数学模型中， 随机化临床试验的补充方法。在目标1中，我们将衡量年龄和艾滋病毒的影响 疾病状态(例如，HIV病毒抑制、CD4计数)对肛门HSIL、HSIL复发和 进展为肛门癌。在目标2中，我们将建立一个临床有效的肛门癌数学模型。 HIV+男性和女性的自然病史，并利用它来确定特定年龄的最佳肛门癌筛查 算法。最后，在目标3中，我们建议确定肛门HSIL的最低必要疗效(按年龄)。 对HIV+男性和女性进行治疗，为筛查提供临床上显著的好处，并最终确定 未来的研究领域，以提高肛门癌筛查的价值。 提出的研究具有创新性，因为它将先进的建模方法与多个数据集应用到 解决一个没有通过经验方法解决的问题。研究团队非常适合，有一个 在艾滋病毒和人乳头瘤病毒流行病学、癌症结果研究和临床护理方面建立了良好的记录， 在开发数学模型为临床决策提供信息方面有丰富的经验。最终的结果 拟议的研究将是针对HIV阳性男性和女性的特定年龄的肛门癌筛查建议 这将为肛门癌预防政策和实践提供信息，并最终降低发病率和死亡率。

PROJECT SUMMARY/ABSTRACT Anal cancer is the second most common non-AIDS defining cancer and a leading cause of morbidity among HIV-infected (HIV+) persons in the United States (US). The incidence of anal cancer increases with age. With nearly 50% HIV+ persons are now 50-years or older, preventative health care in the form of screening is a major public health priority to decrease their risk of developing anal cancer. Because anal cancer is biologically similar to cervical cancer, current guidelines (inferred from cervical cancer literature) recommend screening HIV+ men and women using anal cytology for detection of high-grade squamous intraepithelial lesions (the anal cancer precursor); however, optimal screening regimen (age to start and stop screening as well as optimal screening frequency) for the prevention of anal cancer still remains unknown. Due to the lack of clear understanding of harms versus benefits of screening, only 11% of HIV+ persons had an anal cytology in the preceding year, leading to 50% of diagnoses occurring at stage III or worse when the 5-year survival rate is less than 40%. The goal of the proposed research is to identify appropriate candidates for screening and determine age- specific screening algorithms to reduce anal cancer morbidity and mortality among HIV+ men and women. We will integrate evidence from two large clinical trials and several large databases into mathematical modeling, a complementary approach to randomized clinical trials. In Aim 1, we will measure the impact of age and HIV disease status (i.e., HIV viral suppression, CD4 count) on the incidence of anal HSIL, HSIL recurrence, and progression to anal cancer. In Aim 2, we will develop a clinically-valid mathematical model of anal cancer natural history in HIV+ men and women and use it to determine optimal age-specific anal cancer screening algorithm. Finally, in Aim 3, we propose to determine the minimum necessary efficacy (by age) of anal HSIL treatment for HIV+ men and women to provide clinically significant benefits for screening and finally determine areas of future research to improve the value of anal cancer screening. The proposed research is innovative because it applies advanced modeling approach with multiple datasets to address a problem that has not been solved by empirical methods. The research team is ideally suited, with an established track record in HIV and HPV epidemiology, cancer outcomes research, and clinical care, having substantial experience in developing mathematical models to inform clinical decision making. The end results of the proposed study will be age-specific anal cancer screening recommendations for HIV+ men and women that will inform anal cancer prevention policies and practice and ultimately reduce morbidity and mortality.