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一直是使用最广泛和成功的成功之一 几十年来，北美的公共卫生筛查干预措施。但是，有重大局限 仅细胞学作为筛查测试，导致数千例可预防的死亡。高敏感的分子工具 为了检测高危HPV，宫颈癌的原因有望改变宫颈癌筛查 美国和加拿大的计划。预计基于HPV的筛查将降低宫颈癌率 与细胞学相比，由于HPV对癌前病变的敏感性提高，因此增长了30％。有了改进 HPV测试的负预测值，筛查间隔可以扩展到每4-5年，导致 大量的医疗保健节省。尽管有这些优势，但由于检测到HPV的特异性丧失 不会导致疾病的短暂感染，尤其是在年轻女性中，导致了两倍的数量 其他良好女性的阴道镜治疗。因此，同时防止更少的宫颈癌病例 频繁筛查，基于HPV的筛查可能会对生殖年龄良好的妇女造成意外伤害 如果在没有适当的筛选和分类算法的情况下部署了不可持续的医疗保健系统费用。 与HPV阳性女性中的交替分子方法（即mRNA和基因分型）的分类或采用这些分子。 作为主要屏幕的方法可以提供提高的特异性，而无需降低灵敏度。但是，如果，如何和 当将这些测试最佳地集成到筛选算法中时，在全球范围内仍然是一个关键的知识差距。 目的：本研究解决了北美政策制定者的优先问题，以评估 HPV测试有和没有细胞学共同测试的有效性，确定主要HPV的不利影响 测试，并最终为宫颈癌筛查的最佳筛查算法提供信息。特别是 项目将：1）单个单一的基于HPV的主要筛查的长期疗效（120个月） 与细胞学和共同测试相比，多次筛选； 2）确定3种不同的功效 HPV分类HPV阳性标本的HPV测定，以及对癌前病变的主要筛查； 3）定义 建模种群和系统级别结果的参数不同方案的宫颈癌发生率 方法：来自纵向随机的建立，高度参与队列的参与者（n = 25,223） 比较主要HPV测试与细胞学的对照试验将遵循到120个月。审判参与者是 目前从基线距离基线48个月，并且完全回顾性和前瞻性宫颈癌 筛查，阴道镜和治疗记录，与基于人群的癌症注册中心有联系。基线 通过集中筛查计划，负面妇女将遵循到120个月，而一部分 参与者将获得预期的额外HPV测试。临床终点，灵敏度/特异性和其他 参数将用于数学建模和成本效益分析。