Screening strategies and social determinants of health among people with high risk of anal cancer

摘要： 肛门癌的发病率在过去几十年中几乎翻了一番，沿着增加的是晚期直肠癌。 疾病和死亡率。持续性高危型人乳头瘤病毒（hrHPV）感染导致肛门高级别 鳞状上皮内病变（aHSIL），肛门癌的前兆。肛门癌的风险也是异常的 在某些群体中，艾滋病毒感染者、男男性行为者和艾滋病毒感染率较低的妇女中， 严重的肛门生殖道疾病健康差距进一步助长了这一高比率，因为少数民族，如 作为黑人男男性接触者，aHSIL和癌症的发病率明显更高。因此，aHSIL的早期检测， 特别是在高风险少数群体中，对减少癌症发病率和疾病负担至关重要。然而，在这方面， 目前对aHSIL筛查的建议是基于专家意见和对高危人群的研究， 少数民族稀少。因此，我们提出了这个大规模的多点研究，以探讨潜在的筛选标志物 针对aHSIL，特别关注高风险少数群体。此外，只有一小部分被诊断为 与aHSIL将发展癌症，但治疗建议是所有的aHSIL，导致显着的过度- 治疗，导致不必要的副作用和成本增加。开发可靠的标记物至关重要， 对aHSIL进展和消退风险进行分层。考虑到局部DNA甲基化的重要性， 因此，我们将检测DNA甲基化， 免疫学特征以鉴定aHSIL后癌症风险分层的标志物。检查局部免疫 这些反应也可能有助于阐明有针对性的免疫方法和取得更好的结果。 此外，鉴于肛门癌发病率和结局的差异以及越来越多的认识到 社会决定因素对健康的影响，包括艾滋病毒护理，HPV感染和癌症筛查，我们将 研究社会决定因素是否在aHSIL的流行和清除中发挥关键作用。我们将招募 来自埃默里大学和迈阿密大学的500名肛门癌高危少数族裔男女， 在那里，我们有很大一部分不同的人口，包括美国出生的黑人，加勒比黑人，拉丁裔， 男男性接触者我们将每年跟踪他们长达两年。总体而言，拟议的研究提供了一个独特的 有机会检查高危少数群体中早期aHSIL筛查急需的证据。的 甲基化结果对筛查检测到的aHSIL的风险分层至关重要，并可转化为 筛选免疫和炎症特征将识别与肿瘤进展相关的改变 并随后告知有针对性的免疫干预措施，以获得更好的结果。记录以下方面的重要性 社会决定因素将提供宝贵的建议，以减少健康差距，改善筛查， 结果，并降低高风险少数群体中肛门癌的发病率。

Abstract: The incidence of anal cancer has almost doubled during the past decades, along with increased advanced disease and mortality. Persistent high-risk human papillomavirus (hrHPV) infection leads to anal high-grade squamous intraepithelial lesion (aHSIL), the precursor for anal cancer. Anal cancer risk is also exceptionally high among certain groups: people living with HIV, men having sex with men (MSM), and women with lower high-grade anogenital tract diseases. Health disparity further contributes to this high rate, as minorities, such as Black MSM, have a significantly higher rate of aHSIL and cancer. Thus, early detection of aHSIL, particularly among high-risk minorities, is crucial to reduce cancer incidence and disease burden. However, the current recommendation for aHSIL screening is based on expert opinions, and research on high-risk minorities is scarce. Thereby, we propose this large multisite study to investigate potential screening markers for aHSIL, with a specific focus on high-risk minorities. Furthermore, only a small portion of those diagnosed with aHSIL will develop cancer, yet the treatment recommendation is for all aHSIL, resulting in significant over- treatment, leading to unnecessary side effects and increased cost. It is crucial to develop reliable markers to stratify risks of aHSIL progression and regression. Given the importance of local DNA methylation and the immune environment to viral stimulus and carcinogenesis, hence, we will examine DNA methylation and immunological profiles to identify markers for cancer risk stratification after aHSIL. Examining local immune responses may also shed light on targeted immunotherapeutic approaches and for better outcomes. Additionally, given the disparities in anal cancer incidence and outcomes and the increasingly recognized impact of social determinants on health, including in HIV care, HPV infection, and cancer screening, we will examine whether social determinants play a pivotal role in aHSIL prevalence and clearance. We will recruit 500 minority men and women at high risk for anal cancer from Emory University and the University of Miami, where we have a large portion of diverse populations, including US born Blacks, Caribbean Blacks, Latinx, and MSM. We will follow them yearly for up to two years. Overall, the proposed study provides a unique opportunity to examine the much-needed evidence on early aHSIL screening among high-risk minorities. The methylation results will be crucial to stratify risks of screen-detected aHSIL and could be translated to screening. The immune and inflammatory profile will identify alterations associated with neoplastic progression and subsequently inform targeted immune interventions for better outcomes. Documenting the importance of social determinants will provide invaluable recommendations to reduce health disparities, improve screening outcomes, and decrease the incidence of anal cancer among high-risk minorities.