Project 1: Urine sampling for HPV infection and methylation testing for cervical cancer screening among women living with HIV in Malawi and South Africa

项目 1：马拉维和南非艾滋病毒感染妇女的尿液采样以检测 HPV 感染，并进行甲基化检测以筛查宫颈癌

• 批准号: 10652392
• 负责人: Carla J Chibwesha
• 金额: $ 22.81万
• 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/10652392
• 关键词: Accounting; Address; Affect; Africa; Africa South of the Sahara; African; Area; Cancer Detection; Cervical; Cervical Cancer Screening; Cessation of life; Clinic; Clinical; Collection; Colposcopy; Detection; Diagnosis; Diagnostic Procedure; Disease; Disparity; Enrollment; Epidemic; Generations; Genes; Goals; HIV; HIV Seronegativity; HIV Seropositivity; HPV-High Risk; High Risk Woman; Human; Human Papilloma Virus Vaccination; Human Papillomavirus; Human immunodeficiency virus test; Human papilloma virus infection; Incidence; Kaposi Sarcoma; Lesion; Lymphoma; Malawi; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Measures; Methods; Methylation; Molecular; Oncogenic; Pelvic Examination; Performance; Policies; Population; Predictive Value; Prognosis; Provider; Public Health; Random Allocation; Reporting; Research; Resource-limited setting; Resources; Risk; Rural; Sampling; Sensitivity and Specificity; Services; Site; South Africa; Specificity; Specimen; Testing; Triage; United States; Urine; Vaccination; Vulnerable Populations; Woman; Work; burden of illness; cervical biopsy; cervicovaginal; cost effective; follow-up; high risk; innovation; low and middle-income countries; methylation testing; mortality; novel; population based; premalignant; sample collection; screening; treatment strategy

ABSTRACT: PROJECT 1: Urine sampling for HPV infection and methylation testing for cervical cancer screening among women living with HIV in Malawi and South Africa Cancer incidence, mortality, and disparities are projected to rise at staggering rates. It is estimated, for example, that cancer will kill one million Africans each year by 2030, with invasive cervical cancer (ICC) accounting for the most cancer deaths in African women. Although global policy seeks to rapidly expand access to human papillomavirus (HPV) vaccination and cervical cancer screening in the coming decade, practical efforts to eliminate cervical cancer in low- and middle-income countries (LMICs) remain limited. This gap leaves generations of women needlessly at risk for ICC, with HIV-positive (HIV+) women particularly vulnerable. The need for cost-effective and scalable screening and treatment strategies to reduce ICC is therefore substantial. There is also an urgent need for quality evidence directly applicable to HIV+ women in LMICs, who face the highest risk of HPV infection, cervical precancer (CIN2/3), and ICC. The central hypothesis of our proposal is that the use of self-collected samples to test for HPV infection has the potential to increase cervical screening coverage in clinical settings where pelvic examinations are not routinely performed. We will validate urine-based HPV testing among HIV+ women attending cervical screening clinics at two strong research sites in Malawi and South Africa. As primary HPV screening is highly sensitive but only moderately specific for CIN2/3 and ICC, we will also validate a novel S5 methylation test for triage of women who screen positive for HPV. In Aim 1, we will enroll 925 HIV+ women and evaluate high-risk HPV testing in urine, self-collected cervicovaginal, and provider-collected cervical samples for the detection of CIN2/3 and ICC (CIN2+). We will report HPV positivity in the 3 sample types and compare the sensitivity, specificity, and positive and negative predictive values (PPV and NPV) for CIN2+ detection between the sample types. In Aim 2, we will evaluate S5 methylation as a triage test for HIV+ women with HPV positive results. For each sample collection method (urine, self, and provider), we will calculate PPV, NPV, sensitivity, and specificity of S5 triage testing for CIN2+. We will also report the number of colposcopy referrals per CIN2+ case detected with and without S5 triage. Our proposed project will be the first to validate urine-based HPV testing among HIV+ women and the first to compare the clinical performance of S5 triage testing using urine, self, and provider-collected samples in an LMIC setting. If successful, our findings will have broad relevance for HIV+ women in both resource-rich and resource-poor regions worldwide, including rural and remote areas of the U.S.

摘要：项目1：HPV感染和宫颈癌甲基化测试的尿液采样 在马拉维和南非的艾滋病毒妇女中筛查 癌症的发病率，死亡率和差异预计会以惊人的速度上升。估计 例如，到2030年，癌症每年将杀死一百万的非洲人，侵入性宫颈癌（ICC） 占非洲妇女癌症死亡最多的原因。尽管全球政策试图快速扩展 在未来十年中，获得人乳头瘤病毒（HPV）疫苗接种和宫颈癌筛查， 在低收入国家（LMIC）中消除宫颈癌的实践努力仍然有限。这 缺口使几代女性不必要地面临ICC的风险，尤其是HIV阳性（HIV+）女性 易受伤害的。需要具有成本效益和可扩展筛查和减少ICC的治疗策略的需求是 因此很大。迫切需要直接适用于艾滋病毒+妇女的质量证据 LMIC面临着HPV感染，宫颈预科剂（CIN2/3）和ICC的最高风险。 我们提案的核心假设是使用自我收集的样品测试HPV感染的 在不是骨盆检查的临床环境中增加宫颈筛查覆盖率的潜力 通常执行。我们将验证参加宫颈的HIV+妇女中基于尿液的HPV测试 在马拉维和南非的两个强大的研究地点进行筛查诊所。由于主要的HPV筛选是 高度敏感但仅针对CIN2/3和ICC，我们还将验证一种新型的S5甲基化 测试筛选HPV阳性的女性分类。 在AIM 1中，我们将注册925 HIV+女性，并评估尿液中的高风险HPV测试 宫颈阴道和提供者收集的宫颈样品，用于检测CIN2/3和ICC（CIN2+）。我们将 报告3种样本类型中的HPV阳性，并比较敏感性，特异性以及阳性和阴性 样品类型之间的CIN2+检测的预测值（PPV和NPV）。在AIM 2中，我们将评估S5 甲基化作为HPV阳性结果的HIV+女性的分类测试。对于每个样本收集方法 （尿液，自我和提供者），我们将计算CIN2+S5分诊测试的PPV，NPV，灵敏度和特异性。 我们还将报告每个CIN2+病例的阴道镜转介的数量，并没有S5分类。 我们提出的项目将是第一个验证艾滋病毒+妇女中基于尿液的HPV测试的项目，也是第一个进行的。 比较使用尿液，自我和提供者收集的样品的S5分诊测试的临床性能 LMIC设置。如果成功，我们的发现将与资源丰富的艾滋病毒+妇女具有广泛的意义 全球范围内的资源贫乏地区，包括美国的农村和偏远地区