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

肛门癌高危人群的筛查策略和健康社会决定因素

• 批准号: 10762863
• 负责人: LISA C. FLOWERS
• 金额: $ 104.65万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-12 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10762863
• 关键词: ASCL1 gene; African Caribbean; Anus; Biological Markers; Biopsy; Black Populations; Caribbean region; Caring; Cells; Central America; Cervical; Clinical; Consumption; Cytology; DNA Methylation; Data; Development; Diagnosis; Discrimination; Disease; Disparity; Dysplasia; Early Diagnosis; Environment; Epigenetic Process; Expert Opinion; Goals; Guidelines; HIV; HPV-High Risk; Health; High Risk Woman; Human papilloma virus infection; Immune; Immune Targeting; Immune response; Immunologics; Immunotherapeutic agent; Incidence; Individual; Inflammation; Inflammatory; Inflammatory Response; Latino Population; Latinx; Lesion; Literature; Longitudinal Studies; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of anus; Measures; Methods; Methylation; Minority; Minority Groups; Minority Men; Minority Women; Neighborhoods; Oncogenic; Outcome; Patient Triage; Patients; Performance; Persons; Play; Population Heterogeneity; Poverty; Precancerous Conditions; Prevalence; Recommendation; Reduce health disparities; Research; Resolution; Risk; Risk Factors; Role; Sample Size; Sampling; Screening for cancer; Sensitivity and Specificity; Site; South America; Squamous intraepithelial lesion; Stimulus; Time; Translating; Universities; Viral; Vulva; Woman; advanced disease; biomarker identification; black men; burden of illness; cancer invasiveness; cancer risk; carcinogenesis; chronic infection; cost; design; disparity reduction; ethnic diversity; evidence base; food insecurity; health disparity; high risk; high risk population; housing instability; immunological intervention; immunoregulation; improved; men who have sex with men; men who have sex with men and women; methylation biomarker; mortality; overtreatment; racial disparity; recruit; risk stratification; screening; screening guidelines; side effect; social determinants; social health determinants; tumor progression; tumor-immune system interactions

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.

抽象的： 在过去的几十年中，肛门癌的发病率几乎翻了一番，而高级 疾病和死亡率。持续的高风险人乳头瘤病毒（HRHPV）感染导致肛门高级 鳞状上皮病变（AHSIL），肛门癌的前体。肛门癌的风险也异常 在某些群体中很高：患有艾滋病毒的人，男性与男性发生性关系（MSM）和较低的女性 高级肛门生殖道疾病。健康差异进一步有助于这一高率，因为少数族裔，这样 作为黑色MSM，AHSIL和癌症的发生率明显更高。因此，早期发现Ahsil， 特别是在高风险少数民族中，对于减轻癌症发病率和疾病负担至关重要。然而， 当前对AHSIL筛查的建议是基于专家意见，并研究高风险 少数民族很少。因此，我们提出了这项大型多站点研究，以研究潜在的筛选标记 对于AHSIL，特别关注高风险少数民族。此外，只有一小部分被诊断 与Ahsil一起将患癌症，但治疗建议是针对所有AHSIL的，导致了明显的过度 治疗，导致不必要的副作用和成本增加。开发可靠的标记至关重要 分层AHSIL进展和回归的风险。考虑到局部DNA甲基化和 免疫环境对病毒刺激和致癌作用，因此，我们将检查DNA甲基化和 免疫学特征以识别AHSIL后癌症风险分层的标记。检查局部免疫 反应还可以阐明有针对性的免疫治疗方法和更好的结果。 此外，鉴于肛门癌发病率和结果的差异以及越来越公认的 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 检查社会决定因素是否在AHSIL的患病率和清除率中起关键作用。我们将招募 500名来自埃默里大学和迈阿密大学的肛门癌高风险的少数民族男女， 我们拥有大量人群的地方，包括我们出生的黑人，加勒比海黑人，拉丁裔和 MSM。我们将每年关注他们最多两年。总体而言，拟议的研究提供了独特的 有机会检查有关高风险少数民族早期AHSIL筛查的急需证据。这 甲基化结果对于分层屏幕检测AHSIL的风险至关重要，可以翻译成 筛选。免疫和炎症性特征将确定与肿瘤进展相关的改变 随后，为有针对性的免疫干预措施提供了更好的结果。记录重要性 社会决定因素将提供宝贵的建议，以减少健康差异，改善筛查 结局，并降低高危少数民族中肛门癌的发生率。