Characterization of the cervical fungal communities modulating high-risk HPV infections in Hispanic Women Living with HIV (WLWH)

总体组件摘要-父U54 人类乳头瘤病毒(HPV)相关癌症是拉丁语国家发病率和死亡率的主要原因 美洲和加勒比地区。除了普遍的HPV疫苗接种计划外，具有成本效益的战略是 需要加强对癌前病变的早期发现和改进非侵入性管理 艾滋病毒阳性的女性和男性。人们对新的艾滋病毒筛查技术的表现知之甚少- 拉丁美洲的积极女性。加州-墨西哥-波多黎各(坎波)联盟将演出 三项临床研究集中在#年艾滋病毒阳性妇女中预防宫颈癌 墨西哥和波多黎各。研究1将检查宫颈高级别鳞状细胞癌的新筛查算法 墨西哥和波多黎各4000名HIV阳性妇女的上皮内病变(HSIL)。这项研究将评估 分类策略，包括液体细胞学，高危HPV DNA的护理点基因分型，E6/7 癌蛋白表达，病毒和宿主甲基化检测HIV阳性妇女宫颈HSIL。我们 假设一个高灵敏度的测试，然后是一个高特异性的测试，将提供最佳的 宫颈HSIL在该人群中的敏感性、特异性和预测价值。我们还将筛查1000名艾滋病毒- 男男性接触者(MSM)肛门HSIL阳性以确定我们HSIL为肛门HSIL的男性 治疗研究(研究2和3)，并使用相同的测试评估肛门HSIL筛查算法 那些在宫颈做的手术。通过筛查发现的宫颈和肛门HSIL病例 研究表明，Campo联盟还将开发和实施两个随机安慰剂对照 HSIL的治疗研究。研究2将评估使用肛门益生菌对肛门和宫颈的影响 600名HIV阳性妇女的微生物群及其与肛门和宫颈HSIL回归的关系 以及在那些没有病变的人中，高危HPV DNA持久性的降低。研究3将评估 多价复制缺陷型腺病毒治疗性HPV疫苗治疗的安全性和有效性 300例HIV阳性男女宫颈和肛门HSIL及其免疫应答相关因素的研究 回归。总之，建议的研究旨在开发治疗宫颈癌和肛门癌的新策略。 对艾滋病毒阳性成年人的预防。Campo财团将包括三个核心，以支持 临床试验方案的实施：(1)中央实验室核心；(2)数据管理和 统计核心；和(3)行政和协调核心。此外，警方内部的调查人员 Campo财团将提供指导，支持来自墨西哥和波多黎各的早期职业调查人员 RICO，培养了专注于HPV相关癌症和艾滋病毒的下一代癌症研究人员 区域。通过其创新科学与研究能力建设和指导的独特结合， 我们预计坎波联盟将对宫颈癌和肛门癌的预防工作产生重大影响 在拉丁美洲和加勒比地区。

ABSTRACT OF THE OVERALL COMPONENT - PARENT U54 Human papillomavirus (HPV)-associated cancers are major causes of morbidity and mortality in the Latin American and Caribbean region. Beyond universal HPV vaccination programs, cost-effective strategies are needed to enhance early detection and improve non-invasive management of precancerous lesions among HIV-positive women and men. Little is known about the performance of newer screening technologies in HIV- positive women in Latin America. The California-Mexico-Puerto Rico (CAMPO) Consortium will perform three clinical research studies focused on the prevention of cervical cancer among HIV-positive women in Mexico and Puerto Rico. Study 1 will examine new screening algorithms for cervical high-grade squamous intraepithelial lesions (HSIL) in 4000 HIV-positive women in Mexico and Puerto Rico. This study will evaluate triage strategies that include liquid-based cytology, point-of-care genotyping for high-risk HPV DNA, E6/7 oncoprotein expression, and viral and host methylation to detect cervical HSIL among HIV-positive women. We hypothesize that a test with high sensitivity, followed by a test with high specificity, will provide for optimal sensitivity, specificity and predictive value for cervical HSIL in this population. We will also screen 1000 HIV- positive men who have sex with men (MSM) for anal HSIL to identify men with anal HSIL for our HSIL treatment studies (Studies 2 and 3) and evaluate anal HSIL screening algorithms using the same tests as those being done in the cervix. Through the cases of cervical and anal HSIL identified in these screening studies, the CAMPO Consortium will also develop and implement two randomized placebo-controlled treatment studies for HSIL. Study 2 will evaluate the impact of anogenital probiotic use on anal and cervical microbiota profiles and the relationship to anal and cervical HSIL regression in 600 HIV-positive women and men as well as reduction of high-risk HPV DNA persistence among those with no lesions. Study 3 will evaluate the safety and efficacy of a multivalent replication-defective adenovirus-based therapeutic HPV vaccine to treat cervical and anal HSIL in 300 HIV-positive women and men and identify immune response correlates of HSIL regression. Together, the proposed studies aim to develop novel strategies for cervical and anal cancer prevention for HIV-positive adults. The CAMPO Consortium will include three Cores to support the implementation of the Clinical Trials Program: (1) a Central Laboratory Core; (2) a Data Management and Statistical Core; and (3) an Administrative and Coordinating Core. Furthermore, investigators within the CAMPO Consortium will provide mentorship to support early career investigators from Mexico and Puerto Rico, fostering the next generation of cancer researchers focused on HPV-related cancers and HIV with the region. Through its unique combination of innovative science with research capacity-building and mentorship, we expect the CAMPO Consortium to have a substantial impact on cervical and anal cancer prevention efforts in the Latin American and Caribbean region.