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 本申请是为了响应被标识为NOT-CA的特别利益通知（NOSI）而提交的- 22-036.浸润性宫颈癌（ICC）仍然是两个国家弱势群体的公共卫生问题。 1每年，全世界约有342，000人死于ICC， 85%的死亡发生在中低收入国家。1 ICC可通过人乳头瘤病毒（HPV）疫苗接种预防， 筛查和治疗宫颈上皮内瘤变2或更高（CIN 2+）。2然而，获得这些 国际刑事法院预防战略仍然有限，特别是在中低收入国家，在撒哈拉以南非洲更是如此 由于感染艾滋病毒的妇女（WLWH）持续感染HPV的风险增加， 上皮内瘤变2级或更高（CIN 2+），ICC。3 -5马拉维是撒哈拉以南非洲国家，拥有世界上最高的ICC。 6在15-49岁的女性中，艾滋病毒感染率为11%， 39%的妇女在WLWH.8 2019年，马拉维启动了一项针对青春期女孩的国家HPV疫苗接种计划， 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 因为他们的年龄，因此将保持未接种疫苗。即使青少年普遍接种HPV疫苗， 尽管如此，预计ICC死亡率在几十年内不会随之下降。 快速HPV检测引起了人们的兴趣，因为它允许当天筛查和治疗ICC预防策略。 AmpFire® HPV基因分型系统是由Atila开发的独特核酸扩增技术 biosystems公司它使用一种低成本的便携式仪器， HPV检测结果在大约一个小时，可用于干拭子。因此，hrHPV基因分型相同- AmpFire®可在中低收入国家实施为期一天的HPV筛查和治疗计划。为此，补充 研究项目，我们计划评估不同样本类型的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基因型具有最高的 在马拉维利隆圭的627个WLWH中，331个hrHPV+的子集对CIN 2+的敏感性。这些 我们的U 54资助的研究（U 54 CA 254564）已经招募了女性，并对其进行了随访，该研究评估了 另一种潜在的分诊测试S5甲基化的性能，用于检测WLWH中的CIN 2+。 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， 收集的宫颈阴道和提供者收集的宫颈样本，用于检测不同的高危 WLWH中的HPV基因型。目的2：探索尿液中检测到的hrHPV基因型， 自我收集的宫颈阴道和提供者收集的宫颈样本对 检测CIN 2+。目的3：探讨在自行采集的尿液中检出的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