(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（由适用提供）：美国的艾滋病毒感染人群正在老化，一半以上居住在美国，年龄在50岁以上。不幸的是，抗逆转录病毒疗法 肛门癌最常见于与男性发生性关系的艾滋病毒感染男性中发生的，而感染HIV的MSM是肛门HPV-16感染的最高风险，80-90％的肛门癌和肛门高级鳞状鳞状上皮内病变（HSIL）的病因（HSIL），是肛门癌的前体。肛门癌在普通人群中也是高龄的癌症，与各个年龄段的男性相比，被诊断出患有肛门癌的可能性高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，感染HIV的和未感染的50岁以上的MSM构成了一个理想的人群，在该人群中解决了挑衅性的问题“ PQ4：衰老和HIV感染的生物学如何在各种癌症的发展中相互作用？”年龄有助于增加癌症风险的机制尚不清楚。与年轻人相比，老龄化的人口有证据表明感染增加，并且这些可能导致HPV持续的HPV感染和HSIL清除率降低。慢性炎症也常见于HIV感染的个体。我们建议进行一项研究，以评估年龄组（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，以确定这些年龄较大的年龄段的肛门HPV/HSIL的患病率，并研究它们与包括炎症生物标志物的衰老生物标志物的关联。然后，我们将每六个月跟随男性3年，他们是肛门HPV-16 DNA阳性，但没有HSIL对HSIL的诊断，以评估他们是否持续HPV-16和事件HSIL。我们将同样跟随肛门HPV-16 DNA阴性的男性，并且对肛门HPV-16感染的入射和/或重新激活的HSIL-阴性。在每个前瞻性队列中，我们将评估研究结果与衰老生物学的生物标志物之间的关系。具体目的：1）确定肛门HPV感染和肛门HSIL的年龄特异性患病率，以及它们与感染和衰老HIV感染和未感染的50岁以上MSM的生物标志物的关联。 2）确定肛门HPV-16感染的持续性和肛门HSIL的发病率在一组HIV感染和未感染50岁以上的MSM的同类中，基线时不受肛门HPV-16感染，但没有肛门HSIL，但没有肛门HSIL，但它们与感染和老化的生物标志物的关系。 3）确定新近检测到的肛门HPV-16感染和肛门HSIL的入射在一组HIV感染和未感染的MSM中，年龄50岁以上，没有肛门HPV 16感染和基线时HSIL，以及它们与感染和老化的生物标志物的关系。这项研究将在感染有效ART的老年人中提供有关HPV感染/HSIL的第一批数据，并确定衰老生物学在该人群中肛门癌发病机理中的作用。结果将使我们对HIV感染和未感染的群体中肛门癌发病机理的理解。