Natural History of CIN and HPV in HPV Vaccinated Youth with PHIV

接种 HPV 疫苗的感染 PHIV 青少年的 CIN 和 HPV 自然史

基本信息

批准号：
10663930
负责人：
ANNA-BARBARA MOSCICKI
金额：
$ 5.43万
依托单位：
HARVARD SCHOOL OF PUBLIC HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-18 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10663930
关键词：
Adolescent Adult Age Antibody titer measurement Biological Markers Biopsy Cervical Cervical Cancer Screening Child Clinical Colposcopy Cytology Data Development Diagnosis Disease Event Future General Population Genotype Guidelines HIV HIV Infections HPV-High Risk Human Papilloma Virus Vaccination Human Papilloma Virus Vaccine Human Papilloma Virus-Related Malignant Neoplasm Human Papillomavirus Human papilloma virus infection Human papillomavirus 16 Incidence Infant Infection Inflammatory Intravaginal Administration Lesion Malignant Squamous Cell Neoplasm Malignant neoplasm of anus Malignant neoplasm of cervix uteri Marketing Morbidity - disease rate Natural History Negative Staining Oral Pediatric HIV/AIDS Cohort Study Perinatal Perinatal transmission Persons Policies Polygamy Prevalence Prospective, cohort study Protease Inhibitor Protocols documentation Research Resource-limited setting Resources Risk Factors Sampling Self Administration Sex Behavior Specificity Stains Swab Testing Triage Vaccinated Vaccines Vagina Viral Load result Woman Youth biobank high risk population improved malignant mouth neoplasm men metabolomics microbiome oral HPV perinatal HIV prevent prospective screening sexual debut unvaccinated vaccination strategy vaccine access vaccine failure young adult young man young woman

项目摘要

Project Summary/Abstract Worldwide, over 300,000 women die each year from squamous cell cancers (SCC) of the cervix caused by the high risk human papillomavirus (hrHPV). The development of the HPV vaccine has been a transforming event, capable of preventing cervical cancer globally. HIV infection is an established risk factor for HPV persistence, progression to CIN2+, and HPV-associated cancers. The majority of perinatal HPV appears to be transient. However, the ability of infants with perinatal HIV infection (PHIV) to clear this infection is unknown. What is known is that abnormal cytology is one of the more common diagnosed morbidities in PHIV women. One of the pressing questions worldwide is “what is the efficacy in vaccinating PHIV children?” In a recent study within PHACS of HPV-vaccinated youth, we found that those with PHIV had HPV antibody titers lower than uninfected youth and most disturbingly, their rate of abnormal cytology was exceedingly high: the incidence of abnormal cytology was 15.0 and 2.9 /100 person-years for PHIV and uninfected, respectively. It remains unclear whether this reflects vaccine failure or disease due to non-vaccine HPV types. Our findings led to a sub-study within PHACS supported by the NCI to screen women with abnormal cytology with colposcopy and perform HPV genotyping on cervical lesions. This proposal plans to take advantage of women in this sub-study to understand the natural history of CIN 1 or 2. We are proposing the following Aims: Among YAPHIV women who have been vaccinated against HPV, we will examine: 1. the rate of and risk factors for regression and persistence/progression of HPV-associated CIN1 or 2. YAPHIV found to have CIN 1 or 2 will be followed prospectively by colposcopy, cytology and HPV genotyping. 2. the prevalence of CIN 2+ in those testing positive for hrHPV with/without p16-Ki67 dual staining. 3. the rate of and risk factors for regression and persistence/progression of hrHPV infections. Women in aim 2 with normal cytology and no CIN will be followed prospectively by annual cytology and HPV genotyping. Among PHIV Men, we will examine: 4. the prevalence of and natural history of oral HPV in HPV-vaccinated and unvaccinated PHIV men. Oral rinses obtained for PHACS bio-repository in men every three years will be tested for HPV genotyping. In summary, PHACS AMP-Up, a prospective cohort study, is an exceptional opportunity to understand the natural history of hrHPV and CIN 1 or 2 in PHIV women and oral HPV in PHIV men. The results of this study will be critical for developing clinical and policy guidelines for HPV vaccination strategies and cervical cancer screening among young men and women in resourced and resource poor settings.

项目概要/摘要全球每年有超过 300,000 名女性死于宫颈鳞状细胞癌 (SCC) HPV 疫苗的开发是一次变革。能够在全球范围内预防宫颈癌的事件，艾滋病毒感染是 HPV 的既定危险因素。持续存在、进展为 CIN2+ 以及 HPV 相关癌症大多数围产期 HPV 似乎与癌症有关。然而，围产期 HIV 感染 (PHIV) 的婴儿清除这种感染的能力是短暂的。目前尚不清楚，细胞学异常是 PHIV 中最常见的诊断病症之一。全世界面临的紧迫问题之一是“为儿童接种艾滋病毒疫苗的效果如何？” 在 PHACS 最近对接种 HPV 疫苗的青少年进行的一项研究中，我们发现那些感染 PHIV 的人患有 HPV 抗体滴度低于未感染的年轻人，最令人不安的是，他们的细胞学异常率极高：PHIV 和 PHIV 细胞学异常发生率分别为 15.0 和 2.9/100 人年目前尚不清楚这是否反映了疫苗失败或因非疫苗而导致的疾病。我们的发现引发了 NCI 支持的 PHACS 内的一项子研究，以筛查患有 HPV 类型的女性。该提案计划通过阴道镜检查发现异常细胞学并对宫颈病变进行 HPV 基因分型。在这项子研究中利用女性来了解 CIN 1 或 2 的自然史。我们建议以下目标：在已接种 HPV 疫苗的 YAPHIV 女性中，我们将检查： 1. HPV相关CIN1或2的消退和持续/进展的比率和危险因素。发现患有 CIN 1 或 2 的 YAPHIV 将通过阴道镜检查、细胞学和 HPV 进行前瞻性随访基因分型。 2. 在有/没有 p16-Ki67 双重染色的 hrHPV 检测呈阳性的人群中，CIN 2+ 的患病率。 3. 目标 2 中女性 hrHPV 感染消退和持续/进展的比率和危险因素。细胞学检查正常且无 CIN 的患者将前瞻性地进行年度细胞学检查和 HPV 基因分型。在 PHIV 男性中，我们将检查： 4. 接种 HPV 疫苗和未接种 PHIV 男性中口腔 HPV 的患病率和自然史。每三年为男性 PHACS 生物样本库获得的冲洗液将进行 HPV 基因分型测试。总之，PHACS AMP-Up，一项前瞻性队列研究，是了解 PHIV 女性中 hrHPV 和 CIN 1 或 2 的自然史以及 PHIV 男性中口腔 HPV 的自然史。对于制定 HPV 疫苗接种策略和宫颈癌的临床和政策指南至关重要对资源丰富和资源匮乏地区的青年男女进行筛查。