California-Mexico-Puerto Rico Partnership (CAMPO) Center for Prevention of HPV-related Cancer in HIV+ Populations

加州-墨西哥-波多黎各伙伴关系 (CAMPO) 艾滋病毒人群中 HPV 相关癌症预防中心

• 批准号: 10226223
• 负责人: ANA Patricia ORTIZ
• 金额: $ 175.11万
• 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: 2019-09-12 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10226223
• 关键词: AIDS prevention; Adenoviruses; Adult; 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; 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; research study; screening; screening program; skill acquisition; treatment strategy

ABSTRACT OF THE OVERALL COMPONENT 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.

整体组件的摘要 人乳头瘤病毒（HPV）相关的癌症是拉丁语中发病和死亡率的主要原因 美国和加勒比地区。除了普遍的HPV疫苗接种计划之外，具有成本效益的策略是 需要增强早期检测并改善对癌前病变的非侵入性管理 艾滋病毒阳性的男女。关于HIV-新筛查技术的表现知之甚少。 拉丁美洲的积极女性。加利福尼亚 - 墨西哥 - 普鲁托里科（Campo）财团将表演 三项临床研究的重点是预防HIV阳性妇女的宫颈癌 墨西哥和波多黎各。研究1将检查宫颈高级鳞状的新筛选算法 墨西哥和波多黎各的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，包括基于液体的细胞学，高风险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，以检测HIV阳性妇女的宫颈HSIL。我们 假设具有高灵敏度的测试，然后进行高特异性测试，将提供最佳 该人群中宫颈HSIL的敏感性，特异性和预测价值。我们还将筛选1000 HIV- 与男人发生性关系的正面男人（MSM）为肛门HSIL识别我们的HSIL男性 治疗研究（研究2和3），并使用与 那些是在子宫颈中完成的。通过在这些筛查中鉴定的宫颈和肛门HSIL的情况 研究，坎波联盟还将开发和实施两个随机的安慰剂对照 HSIL的治疗研究。研究2将评估肛门生物使用对肛门和宫颈的影响 微生物群的谱以及与600名HIV阳性妇女的肛门和宫颈HSIL回归的关系 在没有病变的患者中，男性以及降低了高风险的HPV DNA持久性。研究3将评估 基于多价复制缺陷型腺病毒的安全性HPV疫苗的安全性和功效 300名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 回归。拟议的研究旨在制定宫颈癌和肛门癌的新策略 HIV阳性成年人的预防。坎波联盟将包括三个核心，以支持 实施临床试验计划：（1）中央实验室核心； （2）数据管理和 统计核心； （3）行政和协调核心。此外，调查人员 Campo Consortium将提供指导，以支持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，重点是HPV相关的癌症和HIV 地区。通过其创新科学与研究能力建设和指导的独特结合， 我们预计坎波联盟对宫颈和肛门癌的预防工作有重大影响 在拉丁美洲和加勒比地区。