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

使用决策分析模型优化艾滋病毒感染者中基于年龄的肛门癌筛查

• 批准号: 10116312
• 负责人: Ashish A. Deshmukh
• 金额: $ 49.06万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-05 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10116312
• 关键词: Acquired Immunodeficiency Syndrome; Address; Adoption; Age; Aging; Algorithms; American; Anus; Area; Biological; CD4 Lymphocyte Count; Cancer Etiology; Cells; Cervical Cancer Screening; Clinical; Clinical Trials; Collaborations; Colorectal Cancer; Cytology; Data; Databases; Detection; Diagnosis; Disease; Epidemiology; Etiology; Frequencies; Future; Goals; Guidelines; HIV; HPV-High Risk; Human Papillomavirus; Human papilloma virus infection; Incidence; Individual; Life Expectancy; Literature; Malignant Neoplasms; Malignant Squamous Cell Neoplasm; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Malignant neoplasm of prostate; Mass Screening; Mathematics; Measures; Methods; Modeling; Morbidity - disease rate; Natural History; Outcomes Research; Patient-Focused Outcomes; Persons; Policies; Population; Prevention; Preventive healthcare; Quality of life; Randomized Clinical Trials; Recurrence; Regimen; Research; Research Design; Risk; Screening for cancer; Sex Behavior; Squamous intraepithelial lesion; Survival Rate; Treatment Effectiveness; Treatment Efficacy; Uncertainty; United States; United States Department of Veterans Affairs; Viral; Woman; Work; base; cancer prevention; clinical care; clinical decision-making; clinical practice; clinically significant; cohort; comparative effectiveness; cost; cost effective; cost effectiveness; data warehouse; efficacy evaluation; experience; high risk; improved; innovation; malignant breast neoplasm; mathematical model; men; men who have sex with men; models and simulation; mortality; multiple datasets; older men; prevent; public health priorities; screening; screening guidelines; screening policy; sex; virtual

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.

项目概要/摘要 肛门癌是第二常见的非艾滋病定义的癌症，也是人群发病的主要原因 美国 (US) 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。和 近 50% 的艾滋病病毒感染者现在年龄在 50 岁或以上，以筛查形式进行的预防性医疗保健是一项 主要公共卫生优先事项是降低患肛门癌的风险。因为肛门癌是生物学上的 与宫颈癌类似，当前指南（从宫颈癌文献推断）建议筛查 HIV+男性和女性使用肛门细胞学检测高级鳞状上皮内病变（ 肛门癌前兆）；然而，最佳筛查方案（开始和停止筛查的年龄以及 预防肛门癌的最佳筛查频率仍然未知。由于缺乏明确 为了了解筛查的危害与益处，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 期或更严重的阶段，而 5 年生存率为 低于40%。 拟议研究的目标是确定合适的筛选候选人并确定年龄 降低艾滋病毒阳性男性和女性肛门癌发病率和死亡率的具体筛查算法。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、CD4 计数）对肛门 HSIL 发生率、HSIL 复发和 进展为肛门癌。在目标 2 中，我们将开发临床有效的肛门癌数学模型 HIV+ 男性和女性的自然史，并用它来确定最佳的特定年龄肛门癌筛查 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） 对艾滋病毒阳性男性和女性进行治疗，为筛查和最终确定提供临床上显着的益处 提高肛门癌筛查价值的未来研究领域。 所提出的研究具有创新性，因为它应用了具有多个数据集的先进建模方法 解决尚未通过经验方法解决的问题。该研究团队非常适合， 在 HIV 和 HPV 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， 在开发数学模型以指导临床决策方面拥有丰富的经验。最终结果 拟议研究的一部分将是针对艾滋病毒阳性男性和女性的特定年龄肛门癌筛查建议 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。