Cervical Cancer, Aging, and Psychological Distress among HIV-positive Women in Mexico and Puerto Rico: An exploratory sub-study of the CAMPO Consortium Clinical Trials Program

墨西哥和波多黎各艾滋病毒阳性女性的宫颈癌、衰老和心理困扰：CAMPO 联盟临床试验计划的探索性子研究

• 批准号: 10310982
• 负责人: ANA Patricia ORTIZ
• 金额: $ 25.27万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10310982
• 关键词: AIDS prevention; Adenoviruses; Adult; Aging; Algorithms; Anus; California; Caribbean region; Cervical; Cervical Cancer Screening; Cervix Uteri; Clinical Research; Clinical Trials; Country; Cytology; DNA; Early Diagnosis; Fostering; General Population; Genotype; HIV; HIV Infections; HIV Seropositivity; HPV-High Risk; High Prevalence; Human Papilloma Virus Vaccination; Human Papilloma Virus Vaccine; Human Papilloma Virus-Related Malignant Neoplasm; Immune response; Infrastructure; Laboratories; Latin America; Latin American; Lesion; Liquid substance; Malignant Neoplasms; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Mentors; Mentorship; Methylation; Mexican; Mexico; Morbidity - disease rate; Oncoproteins; Parents; Performance; Placebos; Population; Predictive Value; Prevalence; Prevention; Probiotics; Puerto Rico; Randomized; Research; Research Personnel; Resources; Risk; Safety; San Francisco; Science; Sensitivity and Specificity; Specificity; Squamous intraepithelial lesion; Technology; Testing; Therapeutic; Triage; Universities; Viral; Woman; base; cancer prevention; cancer risk; career; cervical and anal cancer; cervical cancer prevention; clinical trial implementation; cost effective; data management; improved; innovation; interest; men; men who have sex with men; microbiota profiles; mortality; next generation; novel; novel strategies; point of care; premalignant; program costs; programs; psychological distress; research study; screening; screening program; skill acquisition; treatment strategy

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.

总体组件摘要-PAU 54 人乳头瘤病毒（HPV）相关癌症是拉丁美洲发病率和死亡率的主要原因。 美洲和加勒比区域。除了普遍的HPV疫苗接种计划外，具有成本效益的策略是 需要加强早期发现和改善癌前病变的非侵入性管理， 艾滋病毒抗体阳性的妇女和男子。关于新的艾滋病毒筛查技术的性能知之甚少， 拉丁美洲的积极女性。加利福尼亚-墨西哥-波多黎各（CAMPO）联合体将执行 三项临床研究的重点是预防艾滋病毒阳性妇女的宫颈癌， 墨西哥和波多黎各。研究1将检查宫颈高度鳞状细胞癌的新筛查算法， 在墨西哥和波多黎各的4000名HIV阳性妇女中进行了上皮内病变（HSIL）的研究。本研究将评估 分诊策略，包括液基细胞学检查、高危HPV DNA的即时基因分型、E6/7 癌蛋白表达，以及病毒和宿主甲基化检测HIV阳性妇女宫颈HSIL。我们 假设具有高灵敏度的测试，接着是具有高特异性的测试，将提供最佳的 敏感性、特异性和预测价值。我们还将筛查1000名艾滋病毒感染者- 与男性发生性关系的男性（MSM）肛门HSIL阳性，以确定我们的HSIL肛门HSIL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， 在子宫颈做的手术通过这些筛查中发现的宫颈和肛门HSIL病例 CAMPO联盟还将开发和实施两项随机安慰剂对照研究， HSIL的治疗研究。研究2将评估肛门生殖器益生菌使用对肛门和宫颈的影响。 600名HIV阳性妇女的微生物群特征及其与肛门和宫颈HSIL消退的关系， 男性以及无病变者中高危HPV DNA持续性的降低。研究3将评估 基于多价复制缺陷型腺病毒治疗性HPV疫苗治疗 300例HIV阳性女性和男性的宫颈和肛门HSIL，并确定HSIL的免疫反应相关性 回归分析这些研究旨在为宫颈癌和肛门癌制定新的治疗策略 预防艾滋病毒阳性成人。CAMPO联盟将包括三个核心，以支持 实施临床试验计划：（1）中心实验室核心;（2）数据管理和 （3）行政和协调核心。此外，调查人员在 CAMPO联盟将提供指导，以支持来自墨西哥和波多黎各的早期职业调查人员 里科，培养下一代癌症研究人员专注于HPV相关的癌症和艾滋病毒， 地区通过其创新科学与研究能力建设和导师制的独特结合， 我们希望CAMPO联盟能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。