Addressing emerging health system priorities in cervical cancer prevention: determining optimal strategies for human papillomavirus test-based screening and triage

解决宫颈癌预防中新出现的卫生系统优先事项：确定基于人乳头瘤病毒测试的筛查和分诊的最佳策略

• 批准号: 10241450
• 负责人: Gina Ogilvie
• 金额: $ 28.59万
• 依托单位: UNIVERSITY OF BRITISH COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-13 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241450
• 关键词: Address; Adopted; Adult; Adverse effects; Age; Algorithms; American; Biological Assay; British Columbia; Canada; Cancer Intervention and Surveillance Modeling Network; Cervical Cancer Screening; Clinical; Colposcopy; Complex; Cost Effectiveness Analysis; Cytology; DNA; Data; Databases; Detection; Disease; Early Diagnosis; Eligibility Determination; Facilities and Administrative Costs; Generations; Genotype; HPV-High Risk; Health Expenditures; Health Services; Health Status; Health system; Healthcare; Healthcare Systems; Histologic; Human Papillomavirus; Human Resources; Incidence; Income; Individual; Infection; Infrastructure; Intervention; Investments; Knowledge; Laboratories; Lead; Leadership; Lesion; Link; Malignant neoplasm of cervix uteri; Messenger RNA; Methods; Modeling; Molecular; North America; Outcome; Pap smear; Participant; Pathway interactions; Policy Maker; Population; Predictive Value; Prevention; Productivity; Protocols documentation; Public Health; Randomized Controlled Trials; Recommendation; Records; Relative Risks; Research; Savings; Screening procedure; Sensitivity and Specificity; Shapes; Specificity; Specimen; System; Technology; Testing; Training; Translating; Triage; Uninsured Medical Expense; United States; Use Effectiveness; Woman; Women' s Health; Work; base; cancer prevention; cervical cancer prevention; clinical care; cohort; cost; cost effectiveness; detection assay; effectiveness evaluation; efficacy evaluation; follow-up; health care service; improved; interest; mathematical model; neoplasm registry; population based; premalignant; prevent; preventable death; programs; prospective; reproductive; screening; screening program; tool; trial comparing; young woman

Background: Cytology-based cervical cancer screening has been one of the most widely used and successful public health screening interventions in North America for decades. However, there are significant limitations to cytology alone as a screening test leading to thousands of preventable deaths. Highly sensitive molecular tools for detection of high-risk HPV, the cause of cervical cancer, are poised to transform cervical cancer screening programs in the United States and Canada. HPV-based screening is expected to reduce cervical cancer rates by 30% compared to cytology, due to improved sensitivity of HPV for pre-cancerous lesions. With the improved negative predictive value of HPV testing, screening intervals can be extended to every 4-5 years leading to substantial health care savings. Despite these advantages, the loss of specificity with HPV due to detection of transient infections that do not result in disease, particularly in young women, leads to twice the number of colposcopy treatments in otherwise well women. Thus, while preventing more cervical cancer cases with less frequent screening, HPV-based screening could lead to unintended harm for well women of reproductive age and unsustainable health care system costs if deployed without appropriate screening and triage algorithms. Triage with alternate molecular methods (ie. mRNA and genotyping) in HPV positive women or adopting these methods as a primary screen could offer improved specificity without reducing sensitivity. However, if, how and when to optimally integrate these tests into screening algorithms remains a critical knowledge gap globally. Aims: This study addresses priority questions from North American policy makers to evaluate the effectiveness of HPV testing with and without cytology co-testing, determine adverse effects of primary HPV testing, and to ultimately inform optimal screening algorithms for cervical cancer screening. Specifically the project will: 1) determine the long-term efficacy (120 months) of HPV-based primary screening after a single and multiple screening rounds, compared to cytology and co-testing; 2) determine the efficacy of 3 different HPV assays for triage of HPV positive specimens, and primary screening for precancerous lesions; 3) define parameters for modeling population and systems-level outcomes of different protocols on cervical cancer rates Methods: Participants of an established, highly engaged cohort (n=25,223) from a longitudinal randomized controlled trial comparing primary HPV testing to cytology will be followed to 120 months. Trial participants are currently 48 months years from baseline and have complete retrospective and prospective cervical cancer screening, colposcopy and treatment records, with linkage to a population-based cancer registry. Baseline negative women will be followed to 120 months though the centralized screening program, while a subset of participants will receive prospective additional HPV testing. Clinical endpoints, sensitivity/specificity and other parameters will be used for mathematic modelling & cost-effectiveness analysis.

背景：基于细胞学的宫颈癌筛查是最广泛使用和最成功的筛查之一 北美的公共卫生筛查干预措施已有数十年历史。然而，有很大的限制 仅细胞学作为筛查测试就导致了数千例可预防的死亡。高灵敏度分子工具 用于检测导致宫颈癌的高危 HPV，有望改变宫颈癌筛查 美国和加拿大的项目。基于 HPV 的筛查有望降低宫颈癌发病率 与细胞学检查相比，由于 HPV 对癌前病变的敏感性提高了 30%。随着改进的 HPV检测的阴性预测价值，筛查间隔可以延长至每4-5年一次，从而 节省大量医疗费用。尽管有这些优点，但由于检测到 HPV 而丧失了特异性 不会导致疾病的短暂感染，尤其是年轻女性，会导致感染人数增加一倍 对其他方面健康的女性进行阴道镜检查治疗。因此，在用更少的钱预防更多宫颈癌病例的同时， 频繁筛查、基于 HPV 的筛查可能会对健康的育龄妇女造成意外伤害 如果没有适当的筛查和分类算法，医疗保健系统的成本将不可持续。 使用替代分子方法（即 mRNA 和基因分型）对 HPV 阳性女性进行分类或采用这些方法 作为主要筛选的方法可以在不降低灵敏度的情况下提供更高的特异性。然而，如果、如何以及 何时将这些测试最佳地集成到筛选算法中仍然是全球范围内的一个关键知识差距。 目的：本研究解决了北美政策制定者提出的优先问题，以评估 在有或没有细胞学联合检测的情况下进行 HPV 检测的有效性，确定原发性 HPV 的不良影响 测试，并最终为宫颈癌筛查提供最佳筛查算法。具体来说 项目将： 1) 在单次筛查后确定基于 HPV 的初步筛查的长期疗效（120 个月） 与细胞学和联合测试相比，多轮筛选； 2) 确定3种不同的功效 用于 HPV 阳性标本分类的 HPV 检测，以及癌前病变的初步筛查； 3）定义 用于对不同方案的宫颈癌发病率进行人口和系统级结果建模的参数 方法：来自纵向随机研究的已建立的、高度参与的队列 (n=25,223) 的参与者 比较初级 HPV 检测与细胞学检测的对照试验将进行 120 个月。试验参与者是 目前距基线 48 个月，患有完整的回顾性和前瞻性宫颈癌 筛查、阴道镜检查和治疗记录，并与基于人群的癌症登记处联系起来。基线 通过集中筛查计划，阴性女性将被跟踪 120 个月，而一部分 参与者将接受前瞻性的额外 HPV 检测。临床终点、敏感性/特异性等 参数将用于数学建模和成本效益分析。