Performance of different sample types for high-risk human papillomavirus testing and genotyping for the detection of high grade cervical intraepithelial neoplasia

不同样本类型用于高危人乳头瘤病毒检测和高级别宫颈上皮内瘤变检测基因分型的性能

• 批准号: 10623831
• 负责人: Carla J Chibwesha
• 金额: $ 12.5万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-13 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10623831
• 关键词: Adolescent; Africa South of the Sahara; Age; Cervical; Cervical Intraepithelial Neoplasia; Cervix Uteri; Cessation of life; Country; Detection; Disease; Enrollment; Female; Female Adolescents; Funding; Future; Genotype; Goals; HIV; HPV-High Risk; Health Personnel; Hour; Human Papilloma Virus Vaccination; Human Papillomavirus; Human papilloma virus infection; Immunization Programs; Individual; Malawi; Malignant neoplasm of cervix uteri; Methylation; Nucleic Acids; Performance; Prevalence; Prevention strategy; Provider; Public Health; Research Project Grants; Risk; Sampling; Swab; System; Technology; Test Result; Testing; Thermal Ablation Therapy; Treatment Failure; Triage; Urine; Vaccines; Vulnerable Populations; Woman; cervical cancer prevention; cervicovaginal; cost; follow-up; instrument; interest; low and middle-income countries; mortality; portability; premalignant; prevent; programs; response; screening; unvaccinated

ABSTRACT This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 22-036. Invasive cervical cancer (ICC) remains a public health problem among vulnerable populations in both high and low-and-middle income countries (LMICs).1 Annually, about 342,000 die from ICC worldwide, with over 85% of deaths occurring in LMICs.1 ICC is preventable through human papillomavirus (HPV) vaccination, screening, and treatment for cervical intraepithelial neoplasia 2 or higher (CIN2+).2 However, access to these ICC prevention strategies remains limited, particularly in LMICs, and is compounded in sub-Saharan Africa (SSA) by HIV since women living with HIV (WLWH) are at increased risk of persistent HPV infection, cervical intraepithelial neoplasia 2 or higher (CIN2+), and ICC.3–5 Malawi, a country in SSA, has the world’s highest ICC mortality.6 HIV prevalence is 11% among females age 15-49 years,7 and HPV infection is currently estimated at 39% among WLWH.8 In 2019, Malawi launched a national HPV vaccination program for adolescent girls following a pilot demonstration project.9,10 However, for the near future, most Malawian women will be vaccine-ineligible due to their age and thus will remain unvaccinated. Even if widespread HPV vaccination of adolescents is achieved, the consequent decline in ICC mortality is not anticipated for decades. Rapid HPV testing is attracting interest as it allows for same day screen-and-treat strategies for ICC prevention. The AmpFire® HPV Genotyping System is a unique nucleic acid amplification technology developed by Atila Biosystems, Inc. that genotypes 15 hrHPV subtypes.23,24 It uses a low-cost portable instrument that provides HPV test results in approximately one hour and can be used on dry swabs. Thus, hrHPV genotyping for same- day HPV screen-and-treat programs in LMICs is feasible with AmpFire®. Therefore, for this supplemental research project, we plan to evaluate the performance of different sample types for hrHPV testing using AmpFire® HPV genotyping and explore which individual genotypes by sample type have the highest sensitivity for CIN2+ among a subset of 331 hrHPV+ among the 627 WLWH in Lilongwe, Malawi. These women are already enrolled and being followed up in our U54-funded study (U54CA254564), which evaluates the performance of another potential triage test, S5 methylation, for the detection of CIN2+ in WLWH.25 To achieve our goals, we have the following Specific Aims: Aim 1: Evaluate and compare urine, self- collected cervicovaginal, and provider-collected cervical samples for the detection of different high-risk HPV genotypes among WLWH. Aim 2: Explore which individual hrHPV genotypes detected on urine, self-collected cervicovaginal, and provider-collected cervical samples have the highest sensitivity for detecting CIN2+. Aim 3: Explore which individual hrHPV genotypes detected on urine, self-collected cervicovaginal, and provider-collected cervical samples are associated with thermal ablation treatment failure.

抽象的 该申请是为了响应特殊利益通知（NOSI）而提交 22-036。侵入性宫颈癌（ICC）仍然是脆弱人群中的公共卫生问题 高中和中低收入国家（LMICS）每年约342,000，全球ICC死亡，超越 LMICS中发生的85％的死亡。1ICC是通过人乳头瘤病毒（HPV）疫苗接种的预防的。 筛查和宫颈上皮内肿瘤2或更高（CIN2+）的治疗。2然而，访问这些 ICC预防策略仍然有限，特别是在LMIC中，在撒哈拉以南非洲（SSA）中更加复杂 艾滋病毒以来，艾滋病毒（WLWH）妇女的持续性HPV感染风险增加 上皮内肿瘤2或更高（CIN2+）和ICC.3-5马拉维（SSA国家）拥有世界上最高的ICC 死亡率6 HIV患病率为15-49岁的女性为11％，目前估计7例HPV感染 在2019年的WLWH.8中，39％的马拉维启动了一项全国HPV疫苗接种计划，针对青少年女孩 试点示范项目。9,10但是，在不久的将来，大多数马拉维妇女都将是疫苗不合格的 由于它们的年龄，因此将保持未接种。即使青少年的宽度HPV疫苗是 实现的是，数十年来预计不会导致ICC死亡率的下降。 快速的HPV测试引起了人们的兴趣，因为它允许在同一天进行预防ICC的屏幕和治疗策略。 AMPFIRE®HPV基因分型系统是Atila开发的独特的核酸扩增技术 Biosystems，Inc。基因型15 HRHPV子类型。23,24它使用了提供的低成本便携式仪器 HPV测试在大约一小时内导致，可用于干签。那是相同的HRHPV基因分型 LMICS中的HPV屏幕和治疗程序与AMPFire®是可行的。因此，对于这种补充 研究项目，我们计划评估使用HRHPV测试的不同样本类型的性能 AMPFIRE®HPV基因分型并探索样本类型的哪些单个基因型具有最高 在马拉维利隆威的627 wlwh中，CIN2+的敏感性在331 HRHPV+的子集中。这些 妇女已经被招募并随访了我们的U54资助研究（U54CA254564），该研究评估了 另一个潜在的分类测试S5甲基化的性能，用于检测WLWH.25中的CIN2+ 为了实现我们的目标，我们有以下具体目标：目标1：评估和比较尿液，自我 收集的宫颈样品以检测不同的高风险 WLWH中的HPV基因型。目标2：探索在尿液上检测到的哪些个体HRHPV基因型， 自我收集的宫颈样品对 检测CIN2+。目标3：探索在尿液上检测到的哪些个体HRHPV基因型 子宫颈阴道和提供者收集的宫颈样品与热消融处理有关 失败。