(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: 9753738
• 负责人: JOEL Michael PALEFSKY
• 金额: $ 56.32万
• 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/9753738
• 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）：美国的艾滋病毒感染人口正在老龄化，超过一半的美国人年龄在50岁或以上。不幸的是，抗逆转录病毒疗法 并没有完全恢复健康。肛门癌最常发生在与男性发生性关系的HIV感染男性（MSM）中，HIV感染的MSM感染肛门HPV-16的风险最高，这是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更晚期的癌症，与所有年龄段的男性相比，60岁或60岁以上的男性被诊断患有肛门癌的可能性高出3倍。年龄与HPV感染/HSIL和HIV感染之间的关系知之甚少。因此，50岁以上的艾滋病毒感染和未感染的男男性行为者构成了一个理想的人群，可以解决一个挑衅性的问题“PQ 4：衰老和艾滋病毒感染的生物学如何在各种癌症的发展中相互作用？“年龄导致癌症风险增加的机制尚不清楚。与年轻人相比，老龄化人群有证据表明炎症增加，这些可能导致持续的HPV感染和HSIL清除率降低。慢性炎症也常见于HIV感染者。我们建议进行一项研究，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，以确定肛门HPV/HSIL在这些老年人群中的患病率，并研究其与衰老生物标志物（包括炎症生物标志物）的相关性。然后，我们将每6个月随访一次肛门HPV-16 DNA阳性但未诊断为HSIL的男性，持续3年，评估他们是否存在HPV-16和HSIL事件。我们将同样跟踪肛门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和衰老HIV感染和未感染的MSM年龄50岁以上的生物标志物的相关性。2)在基线时存在肛门HPV-16感染但无肛门HSIL的50岁以上HIV感染和未感染MSM队列中，确定肛门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50岁以上无肛门HPV 16感染和HSIL的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。这项研究将提供关于有效ART的老年HIV感染者中HPV感染/HSIL的第一个数据，并确定衰老生物学在该人群肛门癌发病机制中的作用。这些结果将为我们了解HIV感染和未感染人群中肛门癌的发病机制提供信息。