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

摘要： 在过去的几十年里，随着晚期肛门癌的增加，肛门癌的发病率几乎翻了一番。 疾病和死亡率。持续高危人乳头瘤病毒感染导致肛门高级别 鳞状上皮内病变(AHSIL)，是肛门癌的前兆。肛门癌的风险也是异常的 在某些群体中比例较高：艾滋病毒携带者、男男性行为者(MSM)和女性比例较低 高级别肛门生殖道疾病。健康差距进一步导致了这一高比率，因为少数族裔，如 作为黑人MSM，AHSIL和癌症的发病率明显较高。因此，早期发现AHSIL， 特别是在高危少数群体中，这对减少癌症发病率和疾病负担至关重要。然而， 目前对AHSIL筛查的建议是基于专家的意见，以及对高危人群的研究 少数族裔是稀缺的。因此，我们提出了这项大型多点研究，以研究潜在的筛查标记 针对AHSIL，特别关注高危少数群体。此外，只有一小部分被诊断为 AHSIL会发展为癌症，但治疗建议适用于所有AHSIL，导致显著过量- 治疗，导致不必要的副作用和增加成本。开发可靠的标记是至关重要的 对AHSIL进展和回归的风险进行分层。鉴于局部DNA甲基化的重要性和 免疫环境对病毒刺激和致癌的影响，因此，我们将检测DNA甲基化和 免疫学资料以确定AHSIL后癌症风险分层的标志物。检查局部免疫 反应还可能有助于了解有针对性的免疫治疗方法，并获得更好的结果。 此外，鉴于肛门癌发病率和预后的差异以及人们日益认识到的 社会决定因素对健康的影响，包括在艾滋病毒护理、HPV感染和癌症筛查方面，我们将 检查社会决定因素是否在AHSIL的流行和清除中起关键作用。我们将招募 来自埃默里大学和迈阿密大学的500名患有肛门癌高危少数民族男性和女性， 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，加勒比海黑人，拉丁裔和 MSM。我们将在长达两年的时间里每年跟踪他们。总体而言，拟议的研究提供了一个独特的 有机会对高危少数民族进行AHSIL早期筛查的急需证据进行审查。这个 甲基化结果将对筛查检测到的aHSIL的风险分层至关重要，并可能转化为 放映。免疫和炎症特征将确定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。记录以下内容的重要性 社会决定因素将为减少健康差距、改善筛查提供宝贵的建议 结果，并减少高危少数人群中的肛门癌发病率。

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.