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.

摘要 本申请是为了回应被确认为非CA-CA的特殊利益通知(NOSI)而提交的 22-036。浸润性宫颈癌(ICC)在这两个地区的脆弱人群中仍然是一个公共卫生问题 1每年全世界约有342,000人死于国际刑事法院，其中 85%的死亡发生在LMICs1 ICC可通过接种人类乳头瘤病毒(HPV)疫苗预防， 宫颈上皮内瘤变2级或更高级别的筛查和治疗(CIN2+).2然而，获得这些 国际刑事法院的预防战略仍然有限，特别是在小岛屿发展中国家，而且在撒哈拉以南非洲(SSA)也是如此。 由于艾滋病毒携带者(WLWH)妇女持续感染HPV的风险增加，宫颈 上皮内瘤变2级或更高(CIN2+)，而ICC.3-5马拉维是SSA中的一个国家，拥有世界上最高的ICC 6艾滋病毒在15-49岁女性中的感染率为11%，7人乳头瘤病毒感染目前估计为 8马拉维于2019年为以下青春期女孩启动了全国人乳头状瘤病毒疫苗接种方案 试点示范项目。9，10然而，在不久的将来，大多数马拉维妇女将不符合接种疫苗的条件 由于他们的年龄，因此将继续不接种疫苗。即使青少年普遍接种HPV疫苗 尽管如此，国际刑事法院死亡率的下降预计在几十年内不会出现。 快速HPV检测吸引了人们的兴趣，因为它允许在同一天进行ICC预防的筛查和治疗策略。 AmpFire®HPV基因分型系统是Atila开发的一项独特的核酸扩增技术 BiosSystems，Inc.对15个hrHPV亚型进行基因分型。23，24它使用一种低成本的便携式仪器，提供 HPV检测结果大约需要一小时，可用于干拭子。因此，hrHPV基因分型对同一- 使用AmpFire®，LMIC中的日间HPV筛选和治疗计划是可行的。因此，对于这份补充材料 研究项目，我们计划评估不同类型的样本用于hrHPV检测的性能，使用 AmpFire®HPV基因分型，并探索样本类型中哪些个体的基因型别最高 马拉维利隆圭627个WLWH中331个hrHPV+的子集对CIN2+的敏感性。这些 女性已经在我们的U54资助的研究(U54CA254564)中登记并接受跟踪，该研究评估 另一种潜在的分类测试，S5甲基化，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 采集宫颈阴道标本和提供者采集的宫颈样本用于检测不同高危人群 WLWH中的HPV基因分型。目的2：探讨在尿液中检测到哪些个体hrHPV基因型别， 自我采集的宫颈阴道样本和提供者收集的宫颈样本对 正在检测CIN2+。目的3：探索自己收集的尿液中检测到哪些hrHPV基因类型 宫颈阴道和提供者收集的宫颈样本与热消融治疗有关 失败了。