(PQ4) Anal HPV infection and anal HSIL among HIV-infected MSM aged 50+ years

(PQ4) 50 岁 HIV 感染 MSM 肛门 HPV 感染和肛门 HSIL

• 批准号: 9321130
• 负责人: JOEL Michael PALEFSKY
• 金额: $ 75.64万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9321130
• 关键词: Address; Age; Age-Years; Aging; Anus; Biological Aging; Biological Markers; Biology of Aging; C-reactive protein; Chronic; Cohort Studies; Cross-Sectional Studies; DNA; Data; Detection; Development; Diagnosis; Disease; Elderly; Fibrin fragment D; General Population; HIV; HIV Infections; Health; High Prevalence; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Incidence; Individual; Infection; Inflammation; Interleukin-6; Longevity; Malignant Neoplasms; Malignant neoplasm of anus; Morbidity - disease rate; Outcome Study; Pathogenesis; Phenotype; Population; Prevalence; Prospective cohort; Risk; Role; Squamous intraepithelial lesion; Time; Veterans; age group; aged; aging population; antiretroviral therapy; cancer risk; cohort; frailty; high risk; high risk men; immune function; indexing; men; men who have sex with men; mortality; public health relevance; young men who have sex with men

 DESCRIPTION (provided by applicant):The HIV-infected population in the US is aging and more than half living in the US are 50 years of age or older. Unfortunately, antiretroviral therapy has not restored full health. Anal cancer occurs most frequently among HIV-infected men who have sex with men (MSM) and HIV-infected MSM are at the highest risk of anal HPV-16 infection, the causative agent in 80- 90% of anal cancers , and anal high-grade squamous intraepithelial lesions (HSIL), the precursor to anal cancer. Anal cancer is also a cancer of more advanced age in the general population and men aged 60 years or older are 3 times more likely to be diagnosed with anal cancer compared with men of all ages. Little is known about the relationship between age and HPV infection/HSIL and HIV infection. HIV-infected and uninfected MSM aged 50+ therefore constitute an ideal population in which to address the provocative question "PQ4: How do the biology of aging and HIV infection interact in the development of various cancers?" The mechanisms by which age contributes to increased risk of cancer are not known. The aging population has evidence for increased inflammation compared with younger people, and these may contribute to persistent HPV infection and reduced clearance of HSIL. Chronic Inflammation is also commonly found in HIV-infected individuals. We propose to conduct a study evaluating the interplay between age group (50-59, 60-69, 70+), HPV and HIV infection. We will perform a cross-sectional study to establish the prevalence of anal HPV/HSIL in these older age groups, and study their association with biomarkers of aging including biomarkers of inflammation. We will then follow men every six months for 3 years who are anal HPV-16 DNA-positive but who have no diagnosis of HSIL evaluating them for persistence of HPV-16 and incident HSIL. We will similarly follow men who are anal HPV-16 DNA-negative and HSIL- negative for incidence and/or reactivation of anal HPV-16 infection. In each prospective cohort we will evaluate the relationship between study outcomes and the biomarkers of the biology of aging. Specific Aims: 1) To determine the age-specific prevalence of anal HPV infection and anal HSIL and their association with biomarkers of inflammation and aging HIV-infected and uninfected MSM aged 50+ years. 2) To determine the persistence of anal HPV-16 infection and incidence of anal HSIL in a cohort of HIV-infected and uninfected MSM aged 50+ years with prevalent anal HPV-16 infection at baseline but no anal HSIL, and their relationship to biomarkers of inflammation and aging. 3) To determine the incidence of newly detectable anal HPV-16 infection and anal HSIL in a cohort of HIV-infected and uninfected MSM aged 50+ years without anal HPV 16 infection and HSIL at baseline, and their relationship to biomarkers of inflammation and aging. This study will provide the first data on HPV infection/HSIL among older HIV-infected individuals on effective ART and determine the role of the biology of aging in the pathogenesis of anal cancer in this population. The results wil inform our understanding of the pathogenesis of anal cancer in both HIV-infected and uninfected populations.

 描述（由申请人提供）：美国的 HIV 感染者正在老龄化，超过一半的美国人年龄在 50 岁或以上。不幸的是，抗逆转录病毒治疗 还没有完全恢复健康。肛门癌最常发生在感染 HIV 的男男性行为者 (MSM) 中，感染 HIV 的 MSM 感染肛门 HPV-16 的风险最高，HPV-16 是 80-90% 肛门癌的病原体，以及肛门高级鳞状上皮内病变 (HSIL)（肛门癌的前兆）。肛门癌也是一般人群中较晚期的癌症，60 岁或以上的男性被诊断出患有肛门癌的可能性是所有年龄段男性的 3 倍。关于年龄与 HPV 感染/HSIL 和 HIV 感染之间的关系知之甚少。因此，年龄 50 岁以上的 HIV 感染者和未感染者 MSM 构成了解决“PQ4：衰老生物学和 HIV 感染如何在各种癌症的发展中相互作用？”这一具有挑战性的问题的理想人群。年龄导致癌症风险增加的机制尚不清楚。有证据表明，与年轻人相比，老龄化人口的炎症增加，这可能导致 HPV 持续感染和 HSIL 清除率降低。慢性炎症也常见于艾滋病毒感染者。我们建议开展一项研究，评估年龄组（50-59、60-69、70+）、HPV 和 HIV 感染之间的相互作用。我们将进行一项横断面研究，以确定这些老年群体中肛门 HPV/HSIL 的患病率，并研究它们与衰老生物标志物（包括炎症生物标志物）的关联。然后，我们将每六个月对肛门 HPV-16 DNA 呈阳性但未诊断出 HSIL 的男性进行跟踪，为期 3 年，评估他们的 HPV-16 持续性和意外 HSIL。我们将类似地跟踪肛门 HPV-16 DNA 阴性和 HSIL 阴性的男性肛门 HPV-16 感染的发生率和/或再激活。在每个前瞻性队列中，我们将评估研究结果与衰老生物学生物标志物之间的关系。具体目标： 1) 确定肛门 HPV 感染和肛门 HSIL 的年龄特异性患病率及其与炎症生物标志物和年龄 50 岁以上 HIV 感染者和未感染者 MSM 的关系。 2) 确定一组年龄 50 岁以上、基线时普遍存在肛门 HPV-16 感染但无肛门 HSIL 的 HIV 感染和未感染 MSM 队列中肛门 HPV-16 感染的持续性和肛门 HSIL 的发生率，以及它们与炎症和衰老生物标志物的关系。 3) 确定基线时无肛门 HPV 16 感染和 HSIL 的 50 岁以上 HIV 感染和未感染 MSM 队列中新检测到的肛门 HPV-16 感染和肛门 HSIL 的发生率，以及它们与炎症和衰老生物标志物的关系。这项研究将提供有关接受有效 ART 治疗的老年 HIV 感染者中 HPV 感染/HSIL 的首个数据，并确定衰老生物学在该人群肛门癌发病机制中的作用。这些结果将有助于我们了解艾滋病毒感染者和未感染者中肛门癌的发病机制。