The effectiveness of screening women with lower genital tract neoplasia or cancers for anal cancer precursors

对患有下生殖道肿瘤或癌症的女性进行肛门癌前兆筛查的有效性

• 批准号: 10450160
• 负责人: Elizabeth Chiao
• 金额: $ 84.38万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10450160
• 关键词: Age-Years; Anal carcinoma; Anus; Biological Markers; Biopsy; Cancer Etiology; Carcinoma; Cervical; Cervical Cancer Screening; Characteristics; Clinical; Clinical Trials; Clinical assessments; Cytology; Data; Decision Analysis; Development; Disease; Dysplasia; Effectiveness; Epidemiology; Exposure to; Generations; Goals; Gold; Guidelines; HIV; HPV-High Risk; Healthcare; Histologic; Human Papilloma Virus Vaccination; Human Papilloma Virus Vaccine; Human Papillomavirus; Human papilloma virus infection; Incidence; Lesion; Longitudinal Studies; Malignant Neoplasms; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Malignant neoplasm of vulva; Mathematics; Methods; Modality; Modeling; Morbidity - disease rate; Natural History; Neoplasms; Oncogenic; Patients; Performance; Persons; Population; Prevalence; Prevention; Prevention Guidelines; Preventive measure; Provider; Publishing; Recording of previous events; Registries; Reporting; Resolution; Resources; Risk; Screening for cancer; Sensitivity and Specificity; Site; Squamous cell carcinoma; Squamous intraepithelial lesion; Testing; Vagina; Vulval intraepithelial neoplasia; Woman; age group; aged; cancer prevention; cancer site; comparative; cost; cost effective; cost effectiveness; disease natural history; evidence based guidelines; experience; high risk population; high standard; improved; mathematical model; mortality; multidisciplinary; patient-level barriers; premalignant; prevent; prospective; reproductive tract; screening; screening guidelines; simulation

PROJECT SUMMARY/ABSTRACT We recently reported that SCCA incidence (particularly advanced-stage disease) and mortality rates are increasing rapidly (>3% per year) in the US with notable (>5%/year) increases in women 50 years and older showing that SCCA is one of the fastest accelerating causes of cancer incidence and mortality among all cancer sites. Women with lower genital tract (cervical/vaginal/vulvar) dysplasia or cancer (WLGTN) represent a large population (>200,000 new cases per year) at elevated risk of developing SCCA. We and others have shown that the incidence of SCCA among WLGTN aged 50 years and older is over 20 per 100,000 persons, which is both comparable to the incidence rate among women with HIV (who are the focus of current screening efforts) and is similar to the cervical cancer incidence prior to widespread screening. Furthermore, HPV vaccination is unlikely to decrease SCCA incidence in this population both because WLGTN have already been exposed to oncogenic HPV, and vaccine rates remain low among US women. This highlights an urgent need for studies evaluating possible targeted prevention in the form of anal cancer screening. Our goal is to evaluate the benefits and harms of SCCA screening among WLGTN. Screening for SCCA involves the identification of precancerous anal lesions (high-grade squamous intraepithelial lesions or "aHSILs") using cytologic testing or HPV testing (potentially performed by patients themselves). These lesions (if histologically confirmed) can then be treated, thereby preventing carcinoma development, similar to practices widely endorsed for cervical cancer. To inform guidelines, data regarding screening characteristics, natural history, patient acceptability, the benefits and harms, and cost-effectiveness of screening for SCCA among WLGTN, are urgently needed. We therefore propose a two-site, two-year longitudinal study of 350 HIV uninfected WGLTN aged ≥45 years. The results of this longitudinal study will be used to synthesize a mathematical (simulation) model that will estimate clinical and population-level benefits versus harms and cost-effectiveness associated with different screening approaches. The Specific Aims are: (1A) To evaluate the respective screening test characteristics of anal cytology, clinician-collected and self-collected high-risk HPV (hrHPV) testing, and cytology/hrHPV cotesting compared to the gold standard of high-resolution anoscopy (HRA) exam with biopsy; (1B): To determine baseline anal hrHPV and histologic aHSIL (haHSIL) prevalence and longitudinal risk among WLGTN; (2): To compare patient acceptability and experiences for anal cancer screening strategies among WLGTN; and (3): To develop a mathematical model determining the potential mortality and morbidity benefits, harms, and cost-effectiveness of anal dysplasia screening and/or hrHPV testing in WLGTN. In summary, the proposed multidisciplinary study will generate much-needed data regarding the optimal SCCA screening approach for WLGTN, necessary to inform national screening recommendations for WLGTN. This study will have direct implications for clinical cancer prevention practices.

项目摘要/摘要 我们最近报告说，SCCA的发病率(特别是晚期疾病)和死亡率是 在美国增长迅速(每年增长3%)，其中50岁及以上女性增长显著(每年增长5%) 表明SCCA是癌症发病率和死亡率增长最快的原因之一 癌症地点。患有下生殖道(宫颈/阴道/外阴)发育不良或癌症(WLGTN)的女性代表 人口众多(每年新增病例200,000例)，罹患SCCA的风险较高。我们和其他人有 结果显示，50岁及以上WLGTN人群中SCCA的发病率超过每10万人20人， 这与感染艾滋病毒的妇女(她们是目前筛查的重点)的发病率相当 努力)，与广泛筛查前的宫颈癌发病率相似。此外，人乳头瘤病毒 接种疫苗不太可能降低该人群中SCCA的发病率，因为WLGTN已经 接触过致癌性HPV，美国女性的疫苗接种率仍然很低。这突显了一个紧急的 有必要进行研究，评估以肛门癌筛查为形式的可能的靶向预防。我们的目标是 评价WLGTN人群SCCA筛查的利弊。筛查SCCA涉及到 癌前病变(高度鳞状上皮内病变或“AHSILs”)的鉴别 细胞学检测或HPV检测(可能由患者自己进行)。这些损伤(如果在组织学上 确认)，然后可以治疗，从而防止癌症的发展，类似于广泛的做法 被认可为宫颈癌患者。告知指南、有关筛查特征的数据、自然病史、 在WLGTN中筛查SCCA的患者可接受性、利弊和成本效益 都是迫切需要的。因此，我们建议对350名未感染艾滋病毒的人进行一项为期两年的两点纵向研究 WGLTN患者≥年龄45岁。这项纵向研究的结果将被用来合成一个数学模型 (模拟)将评估临床和人群层面的益处与危害和成本效益的模型 与不同的筛选方法相关联。具体目标是：(1)评估各自的 肛门细胞学、临床医生收集和自行收集的高危HPV(HrHPV)的筛查试验特征 与高分辨率肛门镜(HRA)检查的黄金标准相比，检测和细胞学/hrHPV共同检测 活检；(1B)：确定基线肛门hrHPV和组织学aHSIL(HaHSIL)患病率和 WLGTN的纵向风险；(2)：比较患者对肛门癌的可接受性和经验 WLGTN中的筛选策略；以及(3)：建立确定潜力的数学模型 肛门发育不良筛查和/或hrHPV的死亡率和发病率效益、危害和成本效益 在WLGTN中测试。总之，拟议的多学科研究将产生关于以下方面的急需数据 WLGTN的最佳SCCA筛查方法，对于通知国家筛查建议是必要的 为WLGTN。这项研究将对临床癌症预防实践有直接的影响。