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

项目总结/摘要 肛门癌是第二种最常见的非艾滋病定义的癌症，也是其中发病的主要原因。 美国（US）的HIV感染者（HIV+）。肛门癌的发病率随着年龄的增长而增加。与 近50%的艾滋病毒阳性者现在是50岁或以上，以筛查形式提供的预防性卫生保健是一种 降低他们患肛门癌的风险是主要的公共卫生优先事项。因为肛门癌在生物学上 与子宫颈癌相似，目前的指南（从子宫颈癌文献推断）建议进行筛查， 使用肛门细胞学检测高度鳞状上皮内病变的HIV阳性男性和女性（ 肛门癌前体）;然而，最佳筛查方案（开始和停止筛查的年龄以及 最佳的检查频率），以预防肛门癌仍然是未知的。由于缺乏明确的 了解筛查的利弊，只有11%的艾滋病毒阳性者在2011年进行了肛门细胞学检查。 前一年，导致50%的诊断发生在III期或更糟的5年生存率时， 低于40%。 拟议研究的目标是确定适当的候选人进行筛选，并确定年龄- 具体的筛查算法，以减少肛门癌的发病率和死亡率之间的艾滋病毒阳性的男子和妇女。我们 将把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（即，HIV病毒抑制、CD 4计数）对肛门HSIL发生率、HSIL复发率和 发展成肛门癌在目标2中，我们将开发一个临床有效的肛门癌数学模型 HIV+男性和女性的自然史，并使用它来确定最佳的年龄特异性肛门癌筛查 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） 为HIV阳性男性和女性提供治疗，为筛查提供临床显著益处，并最终确定 未来的研究领域，以提高肛门癌筛查的价值。 所提出的研究是创新的，因为它采用了先进的建模方法与多个数据集， 解决一个尚未被经验方法解决的问题。研究团队非常适合， 在HIV和HPV流行病学、癌症结局研究和临床护理方面建立了良好的记录， 在开发数学模型以指导临床决策方面具有丰富的经验。最终结果 这项研究的一部分将是针对HIV阳性男性和女性的年龄特异性肛门癌筛查建议， 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.