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

项目总结/摘要 在世界范围内，每年有超过300，000名妇女死于宫颈鳞状细胞癌（SCC）， 高危型人乳头瘤病毒（HRHPV）HPV疫苗的发展是一个转变 活动，能够在全球预防宫颈癌。HIV感染是HPV的一个既定危险因素 持续性、进展为CIN 2+和HPV相关癌症。大多数围产期HPV似乎 是短暂的然而，患有围产期HIV感染（PHIV）的婴儿清除这种感染的能力是有限的。 未知已知的是，异常细胞学是PHIV中较常见的诊断发病率之一 妇女世界范围内的一个紧迫问题是“接种PHIV儿童的有效性如何？” 在PHACS最近对HPV疫苗接种青年的一项研究中，我们发现， 抗体滴度低于未感染的青年，最令人不安的是，他们的细胞学异常率为 极高：PHIV的细胞学异常发生率为15.0/100人年和2.9 /100人年， 未感染的，分别。目前还不清楚这是否反映了疫苗失败或疾病，由于非疫苗 HPV类型。我们的研究结果导致了一项由NCI支持的PHACS子研究， 用阴道镜检查细胞学异常，并对宫颈病变进行HPV基因分型。该提案计划 利用本子研究中的女性来了解CIN 1或2的自然史。我们提议 以下目标： 在接种过HPV疫苗的YAPHIV女性中，我们将检查： 1. HPV相关CIN 1或2的消退和持续/进展的发生率和风险因素。 发现有CIN 1或2的YAPHIV将前瞻性地进行阴道镜检查、细胞学检查和HPV检查 基因分型 2. hrHPV检测阳性者中CIN 2+的患病率（有/无p16-Ki 67双重染色）。 3. hrHPV感染消退和持续/进展的发生率和风险因素。aim 2中的妇女 细胞学检查正常且无CIN的受试者将前瞻性随访年度细胞学检查和HPV基因分型。 在PHIV男性中，我们将检查： 4. HPV疫苗接种和未接种PHIV男性中口服HPV的患病率和自然史。口服 将每三年对用于PHACS生物储存库的男性冲洗液进行HPV基因分型测试。 总之，PHACS AMP-Up是一项前瞻性队列研究，是了解 在PHIV女性中hrHPV和CIN 1或2的自然史和在PHIV男性中口腔HPV。本研究结果 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 在资源和资源匮乏的环境中对青年男女进行筛查。

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.