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

• 批准号: 10264954
• 负责人: ANNA-BARBARA MOSCICKI
• 金额: $ 5.54万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 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/10264954
• 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; Failure; 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; Lesion; Malignant Squamous Cell Neoplasm; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; 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; 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; vaccination strategy; vaccine access; young adult; young man; young woman

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.

项目摘要/摘要 在全球范围内，每年有超过30万妇女死于子宫颈的鳞状细胞癌（SCC） 通过高风险人乳头瘤病毒（HRHPV）。 HPV疫苗的开发是一种转变 事件，能够预防全球宫颈癌。艾滋病毒感染是HPV的确定危险因素 持久性，发展为CIN2+和HPV相关癌症。大多数围产期HPV似乎 瞬态。但是，围产期HIV感染（PHIV）清除这种感染的婴儿的能力是 未知。众所周知，异常细胞学是PHIV中最常见的诊断病毒之一 女性。全世界的紧迫问题之一是“接种PHIV儿童的有效性是什么？” 在HPV接种疫苗的青年PHAC的最新研究中，我们发现患有PHIV的人患有HPV 抗体滴度低于未感染的青年，最令人不安的是，它们的异常细胞学速率是 极高的：pHIV的异常细胞学事件为15.0和2.9 /100人年， 分别未感染。目前尚不清楚这是否反映了由于非疫苗的疫苗衰竭或疾病 HPV类型。我们的发现导致了NCI支持的PHAC中的一个子研究，以筛查女性 阴道镜检查异常细胞学，并对宫颈病变进行HPV基因分型。该建议计划 利用这个子研究中的妇女了解CIN 1或2的自然历史。我们正在提议 以下目的： 在接种了HPV疫苗的Yaphiv妇女中，我们将研究： 1。与HPV相关的CIN1或2的回归和持久性/进展的危险因素和风险因素。 Yaphiv发现具有CIN 1或2 基因分型。 2。CIN 2+在HRHPV呈阳性的情况下的患病率，带有/没有P16-KI67双染色。 3。HRHPV感染的回归和持久性/进展的率和风险因素。 AIM 2的妇女2 通过正常的细胞学和CIN，将通过年度细胞学和HPV基因分型遵循。 在PHIV男子中，我们将研究： 4。在HPV接种疫苗和未接种疫苗的PHIV男子中，口服HPV的患病率和自然史。口服 每三年为男性中的PHAC生物重复疗法获得的RIN将进行HPV基因分型的测试。 总而言之，一项前瞻性队列研究PHACS AMP-UP是一个了解 PHIV妇女中HRHPV和CIN 1或2的自然历史以及PHIV男性的口服HPV。这项研究的结果 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 在资源和资源较差的年轻男女中筛选。