Cervical, Anal & Oral HPV Persistence/Adolescent Girls

这项应用建议继续研究一个庞大而独特的市中心青少年/年轻人队列。 妇女(Aya)在西奈山青少年健康中心(MSAHC)进行，其中约95%是 黑人或西班牙裔。我们已经证明早期的四价(4v)HPV疫苗是有效的，尽管有一些 4vHPV型突破性感染。然而，临床研究的终点仍然很少，例如 疫苗的“突破性感染”--HPV类型、非疫苗高危HPV(HrHPV)类型的比率和长期感染 定期HPV疫苗抗体滴度。这些数据对于确定HPV加强剂注射是否使用 对于接种了4v疫苗(正在使用中)的AYA来说，较新的非疫苗(9v)HPV疫苗可能是有保障的 2007-2016年)。直到现在，才有足够的自接种疫苗以来的数据来进行必要的长期跟踪- UP学习。此外，来自我们小组和其他人的数据显示，在4v疫苗中，非疫苗hrHPV感染 接受者正在增加(这引发了人们对“病毒型替换”的担忧)。此外，该项目还将评估 HPV和其他性传播感染(STI)的分子风险因素，在#年处于历史水平 少数AYA，在MSAHC妇女中患病率为30%。MSAHC的队列在提供 衣原体和hrHPV与宫颈阴道微生物群(CVM；a)密切相关的数据 有色人种女性的目标暴露)。最近，我们证明了这些关联可能在一定程度上 CVM对宫颈阴道环境的其他方面的影响，使用一种新的分子NEXT- 世代测序(NGS)分析(MolBV)是在过去的资助期发展起来的。在这里，我们将研究 使用MSAHC在市中心非裔美国人和西班牙裔Aya妇女中合并CVM/细胞因子数据 一群人。我们将招募更多13-19岁接种9v疫苗的女性。据我们所知，这将是 也是第一次对9v在少数民族群体中的现实世界有效性进行纵向研究。我们会跟进的 所有参与者(包括队列中现有的21-25岁的4v疫苗接种者，年龄不超过30岁)使用我们成熟的 宫颈、肛门和口腔脱落细胞样本以及血清的q6mo采集方案 性传播感染，详细的危险行为数据，现在还包括用于测量局部的宫颈阴道芯样本 细胞因子水平。拟议的综合设计将使我们能够达到以下具体目标：(1) 四价(4v)和非疫苗(9v)HPV疫苗的真实世界和长期有效性；(2)因素 影响HPV疫苗效力的因素，如HPV抗体效价、HPVL1衣壳蛋白逃逸突变、 和可能的病毒类型替换；以及(3)CVM和局部细胞因子对HPV和其他 性传播疾病。这项关于难以招募和跟踪的人群的重要流行病学研究将提供前瞻性的 关于接种HPV疫苗的长期影响的数据，是否需要加强注射，以及生物 宫颈阴道微环境对人乳头瘤病毒自然史和性传播感染风险的影响。

This application proposes continued study of a large and unique inner-city cohort of adolescent / young-adult women (AYA) conducted at Mount Sinai Adolescent Health Center (MSAHC) approximately 95% of whom are Black or Hispanic. We have shown the early quadrivalent (4v) HPV vaccine to be effective, despite some breakthrough infections by 4vHPV types. However, there remains a paucity of clinical study endpoints such as “breakthrough infections” of vaccine-HPV types, rates of non-vaccine high-risk HPV (hrHPV) types, and long- term HPV vaccine antibody titers. These data are important for determining whether HPV booster shots using the newer nonavalent (9v) HPV vaccine may be warranted for AYAs who received the 4v vaccine (in use from 2007-2016). Only now is there sufficient time-since-vaccination data to conduct the necessary long-term follow- up studies. Further, data from our group and others show that non-vaccine hrHPV infections in 4v vaccine recipients are increasing (raising concerns of “viral type replacement”). Moreover, this project will assess molecular risk factors for HPV and other sexually transmitted infections (STIs), which are at historic levels in minority AYAs, with a prevalence >30% in MSAHC women. The MSAHC cohort has been unique in providing data on the strong associations of both chlamydia and hrHPV with the cervicovaginal microbiome (CVM; a targetable exposure) in women of color. Most recently, we showed that these associations may be due in part to the effects of the CVM on other aspects of the cervicovaginal milieu, using a novel molecular Next- Generation Sequencing (NGS) assay (molBV) developed this past funding period. Herein, we will study combined CVM / cytokine data in inner-city African American and Hispanic AYA women, using the MSAHC cohort. We will enroll additional women 13-19yo who have received the 9v vaccine. To our knowledge, this will also be the 1st longitudinal study of the real-world effectiveness of the 9v in minority groups. We will follow-up all participants (including existing 4v vaccinees 21-25yo in the cohort, up to age 30) using our well-established protocol of q6mo collection of cervical, anal, and oral exfoliated cell samples, as well as serum, screening for STIs, detailed risk behavior data, and now also including cervicovaginal wick specimens for measuring local cytokine levels. The proposed comprehensive design will allow us to address the following Specific Aims: (1) the real-world, long-term effectiveness of the quadrivalent (4v) and nonavalent (9v) HPV vaccines; (2) factors that impact HPV vaccine effectiveness such as HPV antibody titers, HPV L1 capsid protein escape mutations, and possible “viral type replacement”; and (3) the impact of the CVM and local cytokines on HPV and other STIs. This important epidemiological study of a population difficult to recruit and follow will provide prospective data on the long-term impact of HPV vaccination, whether a booster shot will be required, and the biological underpinnings of the cervicovaginal microenvironment on the natural history of HPV and risk of STIs.