Longitudinal Study of Vaginal Microbiota and Persistent Human Papillomavirus Detection

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Project Summary/Abstract Title: Longitudinal Study of Vaginal Microbiota and Persistent Human Papillomavirus Detection Abstract: In the US, there are about 7 million new genital human papillomavirus (HPV) infections with high-risk oncogenic HPV types each year. About 10% of these, or 700,000 are persistent; this is an important risk factor for cervical dysplasia and invasive cervical cancer. The dynamics of HPV infection and the subsequent development of high-grade cervical intraepithelial neoplasia are not well understood. The proposed study will characterize the temporal relationship of vaginal microbiota associated with Metronidazole treatment of asymptomatic bacterial vaginosis (BV). It will also examine whether Metronidazole treatment of asymptomatic BV is associated with detection of oncogenic HPV and persistence of oncogenic HPV infections. The proposed pilot study will utilize existing vaginal swabs from 80 women followed over six months from the BRAVO study, a randomized controlled open labeled clinical trial examining Metronidazole treatment of asymptomatic BV. The vaginal microbiome will be characterized using high throughput 16s rRNA encoding gene pyrosequencing. The proposed research fits with priorities of the National Cancer Institute (NCI) and National Institute of Allergy and Infectious Disease (NIAID). NCI has prioritized racial and ethnic disparities in the incidence and mortality of certain cancers and prevention or early detection of these cancers in specific populations and NIAID has set “screening, diagnosis and interventions for target populations to determine how to triage various groups for appropriate prevention, treatment and education strategies” as an overarching priority. There are also compelling public health reasons for supporting this application: In spite of the availability of prophylactic HPV vaccination, there are still more than 528,000 new cases and 266,000 deaths worldwide from cervical cancer related to persistent HPV infections each year. This innovative research will complement current HPV vaccine research by providing more data on how the dysbiosis associated with BV allows HPV to bypass vaginal defenses to infect basal epithelial cells—providing information that could contribute to more effective vaccines. It also may help inform treatment guidelines. Finally, it will build research infrastructure and opportunities for student involvement at the largest minority majority institution in the U.S.