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.

项目总结/摘要 我们最近报道了SCCA的发病率（特别是晚期疾病）和死亡率， 在美国迅速增加（>3%/年），50岁及以上女性的增加显著（>5%/年） 表明SCCA是所有癌症发病率和死亡率增长最快的原因之一， 癌症部位。患有下生殖道（宫颈/阴道/外阴）发育不良或癌症（WLGTN）的女性代表了 大量人群（每年新发病例> 200，000例）发生SCCA的风险升高。我们和其他人已经 显示50岁及以上的WLGTN中SCCA的发病率超过每10万人20例， 这与感染艾滋病毒的妇女（目前筛查的重点）的发病率相当， 努力），并与广泛筛查前的宫颈癌发病率相似。此外，HPV 接种疫苗不太可能降低这一人群的SCCA发病率，因为WLGTN已经 美国女性一直暴露于致癌的HPV，疫苗接种率仍然很低。这凸显了一个紧迫的 需要进行研究，以评估肛门癌筛查形式的可能的有针对性的预防。我们的目标是 评估WLGTN中SCCA筛查的益处和危害。SCCA的筛查包括： 使用识别肛门癌前病变（高级鳞状上皮内病变或“aHSIL”） 细胞学检测或HPV检测（可能由患者自己进行）。这些病变（如果在组织学上 证实），然后可以治疗，从而防止癌症的发展，类似于广泛的实践 被批准用于宫颈癌。告知指南、有关筛选特征、自然史的数据， WLGTN中SCCA筛查的患者可接受性、获益和危害以及成本效益， 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为期两年的双中心纵向研究。 年龄≥45岁的WGLTN。这项纵向研究的结果将用于合成一个数学模型， （模拟）模型，用于估计临床和人群水平的获益与危害和成本效益 与不同的筛选方法有关。具体目标是：（1A）评估各自的 肛门细胞学筛查检测特征，临床医生采集和自我采集的高危型HPV（hrHPV） 与高分辨率肛门镜检查（HRA）的金标准相比， （1B）：确定基线肛门hrHPV和组织学aHSIL（haHSIL）患病率， WLGTN中的纵向风险;（2）：比较患者对肛门癌的可接受性和经验 WLGTN之间的筛选策略;（3）：建立一个数学模型，确定潜在的 肛门发育不良筛查和/或hrHPV的死亡率和发病率获益、危害和成本效益 在WLGTN测试。总之，拟议的多学科研究将产生急需的数据， WLGTN的最佳SCCA筛选方法，为国家筛选建议提供信息所必需 关于WLGTN这项研究将对临床癌症预防实践产生直接影响。