Cervical, Anal & Oral HPV Persistence/Adolescent Girls

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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.