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.

整体组成部分摘要 - 父级 U54 人乳头瘤病毒 (HPV) 相关癌症是拉丁地区发病和死亡的主要原因 美洲和加勒比地区。除了普遍的 HPV 疫苗接种计划之外，具有成本效益的策略还包括 需要加强早期发现并改善癌前病变的无创治疗 艾滋病毒呈阳性的女性和男性。人们对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) 联盟将执行 三项临床研究的重点是预防艾滋病毒阳性女性的宫颈癌 墨西哥和波多黎各。研究 1 将检验宫颈高级鳞状细胞癌的新筛查算法 墨西哥和波多黎各 4000 名 HIV 阳性女性的上皮内病变 (HSIL)。本研究将评估 分诊策略，包括液基细胞学、高危 HPV DNA 的护理点基因分型、E6/7 癌蛋白表达以及病毒和宿主甲基化，以检测 HIV 阳性女性的宫颈 HSIL。我们 假设先进行高灵敏度的测试，然后进行高特异性的测试，将提供最佳的结果 该人群中宫颈 HSIL 的敏感性、特异性和预测价值。我们还将筛查 1000 名 HIV- 男男性行为者 (MSM) 肛门 HSIL 呈阳性，以识别患有肛门 HSIL 的男性 治疗研究（研究 2 和 3）并使用与以下相同的测试评估肛门 HSIL 筛查算法 那些在子宫颈中进行的手术。通过这些筛查中发现的宫颈和肛门 HSIL 病例 研究中，CAMPO 联盟还将开发并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的使用对肛门和宫颈的影响 600 名 HIV 阳性女性和女性的微生物群概况及其与肛门和宫颈 HSIL 消退的关系 男性以及无病变人群中高危 HPV DNA 持久性的降低。研究 3 将评估 基于多价复制缺陷型腺病毒的治疗性 HPV 疫苗治疗的安全性和有效性 对 300 名 HIV 阳性女性和男性的宫颈和肛门 HSIL 进行检测，并确定 HSIL 的免疫反应相关性 回归。总之，拟议的研究旨在开发治疗宫颈癌和肛门癌的新策略 艾滋病毒阳性成人的预防。 CAMPO 联盟将包括三个核心来支持 临床试验计划的实施： (1) 中心实验室核心； (2) 数据管理和 统计核心； (3) 行政和协调核心。此外，调查人员在 CAMPO 联盟将提供指导，支持来自墨西哥和波多黎各的早期职业调查员 Rico，培养下一代癌症研究人员，重点研究 HPV 相关癌症和艾滋病毒 地区。通过创新科学与研究能力建设和指导的独特结合， 我们期望 CAMPO 联盟能够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。