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 本申请是为了响应被识别为 NOT-CA- 的特殊利益通知 (NOSI) 而提交的 22-036。侵袭性宫颈癌（ICC）仍然是两国弱势群体的一个公共卫生问题。 高收入和中低收入国家 (LMIC)。1 全世界每年约有 342,000 人死于 ICC，其中超过 85% 的死亡发生在中低收入国家。1 ICC 可以通过接种人乳头瘤病毒 (HPV) 疫苗来预防， 宫颈上皮内瘤变 2 级或更高 (CIN2+) 的筛查和治疗。2 然而，获得这些 ICC 预防策略仍然有限，特别是在中低收入国家，并且在撒哈拉以南非洲 (SSA) 更为复杂 由于感染 HIV 的女性 (WLWH) 持续感染 HPV、宫颈癌的风险增加， 上皮内瘤变 2 级或更高 (CIN2+)，ICC.3-5 马拉维是 SSA 的一个国家，其 ICC 是世界上最高的 6 15-49 岁女性中的艾滋病毒感染率为 11%，7 目前估计 HPV 感染率为 WLWH 中占 39%。8 2019 年，马拉维针对青春期女孩启动了国家 HPV 疫苗接种计划，如下： 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没有资格接种疫苗 由于他们的年龄，因此即使青少年广泛接种 HPV 疫苗，他们仍不会接种疫苗。 如果实现了这一目标，则预计几十年内 ICC 死亡率都不会下降。 快速 HPV 检测引起了人们的兴趣，因为它可以实现 ICC 预防的当天筛查和治疗策略。 AmpFire® HPV 基因分型系统是 Atila 开发的独特核酸扩增技术 Biosystems, Inc. 对 15 种 hrHPV 亚型进行基因分型。23,24 它使用低成本便携式仪器，可提供 HPV 检测大约一小时即可出结果，可用于干拭子，因此，hrHPV 基因分型同样适用。 因此，对于中低收入国家 (LMIC) 的日间 HPV 筛查和治疗计划，AmpFire® 是可行的。 研究项目中，我们计划使用 hrHPV 检测来评估不同样本类型的性能 AmpFire® HPV 基因分型并按样本类型探索哪些个体基因型具有最高的 马拉维利隆圭 627 名 WLWH 中 331 名 hrHPV+ 子集对 CIN2+ 的敏感性。 女性已在我们的 U54 资助的研究 (U54CA254564) 中入组并接受随访，该研究评估 另一种潜在分类测试（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、自我检测 收集宫颈阴道样本和提供者收集的宫颈样本以检测不同的高风险 WLWH 中的 HPV 基因型 目标 2：探索尿液中检测到的个体 hrHPV 基因型。 自行采集的宫颈阴道样本和提供者采集的宫颈样本对于 检测 CIN2+ 目标 3：探索在自行收集的尿液中检测到的个体 hrHPV 基因型。 宫颈阴道和提供者收集的宫颈样本与热消融治疗相关 失败。