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 感染的尿液取样和宫颈癌的甲基化检测 在马拉维和南非对感染艾滋病毒的妇女进行筛查 癌症发病率、死亡率和差异预计将以惊人的速度上升。据估计，对于 例如，到 2030 年，癌症每年将导致 100 万非洲人死于浸润性宫颈癌 (ICC) 非洲女性癌症死亡人数最多。尽管全球政策力求迅速扩大 在未来十年获得人乳头瘤病毒（HPV）疫苗接种和宫颈癌筛查， 低收入和中等收入国家（LMIC）消除宫颈癌的实际努力仍然有限。这 差距使几代妇女面临不必要的 ICC 风险，尤其是艾滋病毒呈阳性 (HIV+) 的妇女 易受伤害的。需要采用具有成本效益且可扩展的筛查和治疗策略来减少 ICC 因此很重要。还迫切需要直接适用于艾滋病毒阳性女性的高质量证据 中低收入国家 (LMIC) 面临 HPV 感染、宫颈癌前病变 (CIN2/3) 和 ICC 的最高风险。 我们提案的中心假设是，使用自行采集的样本来检测 HPV 感染已经 在不进行盆腔检查的临床环境中提高宫颈筛查覆盖率的潜力 常规执行。我们将在就诊宫颈癌的 HIV + 女性中验证基于尿液的 HPV 检测 在马拉维和南非两个强大的研究中心进行筛查诊所。由于初级 HPV 筛查是 对 CIN2/3 和 ICC 高度敏感，但只有中等特异性，我们还将验证一种新的 S5 甲基化 对 HPV 筛查呈阳性的女性进行分类测试。 在目标 1 中，我们将招募 925 名 HIV + 女性，并评估自行收集的尿液中的高危 HPV 检测 宫颈阴道样本和提供者收集的宫颈样本，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 样本类型之间 CIN2+ 检测的预测值（PPV 和 NPV）。在目标 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。对于每种样本采集方法 （尿液、自身和提供者），我们将计算 CIN2+ 的 PPV、NPV、S5 分类测试的敏感性和特异性。 我们还将报告在有或没有 S5 分诊的情况下检测到的每个 CIN2+ 病例的阴道镜转诊数量。 我们提议的项目将是第一个在 HIV + 女性中验证基于尿液的 HPV 检测的项目，也是第一个 比较使用尿液、自身和提供者收集的样本进行 S5 分类测试的临床表现 LMIC 设置。如果成功的话，我们的研究结果将对资源丰富和资源丰富的艾滋病毒阳性女性产生广泛的相关性。 全球资源贫乏地区，包括美国的农村和偏远地区