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

项目摘要/摘要 全世界每年有30多万妇女死于宫颈鳞状细胞癌(SCC) 由高危人乳头瘤病毒(HrHPV)感染。人乳头瘤病毒疫苗的发展是一场变革 这一事件能够在全球范围内预防宫颈癌。艾滋病毒感染是人乳头瘤病毒的既定危险因素 持续性、进展为CIN2+和HPV相关癌症。大多数围产期HPV似乎都是 是短暂的。然而，患有围产期艾滋病毒感染(PHIV)的婴儿清除这种感染的能力是 未知。已知的是，细胞学异常是PHIV最常见的诊断疾病之一。 女人。世界范围内的一个紧迫问题是“为PHIV儿童接种疫苗的效果如何？” 在最近在PHACS内对接种HPV疫苗的年轻人进行的一项研究中，我们发现那些携带PHIV的人感染了HPV 抗体效价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是 非常高：PHIV和PHIV的细胞学异常发生率分别为15.0和2.9/100人年， 分别为未感染。目前尚不清楚这是由于疫苗接种失败还是由于没有接种疫苗导致的疾病。 人乳头瘤病毒类型。我们的发现导致了NCI支持的PHACS内的一项子研究，以筛查患有 阴道镜检查细胞学异常，对宫颈病变进行HPV基因分型。这项提案计划 在这个子研究中利用女性来了解CIN 1或CIN 2的自然历史。 目标如下： 在已接种HPV疫苗的YAPHIV妇女中，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。 被发现患有CIN 1或2的YAPHIV将前瞻性地进行阴道镜、细胞学和HPV检查 基因分型。 2.p16-Ki67双重染色hrHPV阳性组中CIN~(2+)的发生率。 3.hrHPV感染消退和持续/进展的比率和危险因素。《目标2》中的女性 在细胞学正常且无CIN的情况下，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.接种人乳头瘤病毒疫苗和未接种艾滋病毒人乳头瘤病毒男子的口腔人乳头瘤病毒的流行率和自然病史。口头的 每三年为男性PHACS生物储存库获得的漂洗液将进行HPV基因分型测试。 总而言之，PHACS AMP-UP是一项前瞻性队列研究，是了解 HIV感染者中hrHPV和CIN 1或CIN 1或2的自然病史以及HIV感染者中口服HPV的情况。这项研究的结果 将对制定HPV疫苗接种策略和宫颈癌的临床和政策指南至关重要 在资源紧缺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.