Project Summary/AbstractTitle: Longitudinal Study of Vaginal Microbiota and Persistent Human Papillomavirus DetectionAbstract: In the US, there are about 7 million new genital human papillomavirus (HPV) infections withhigh-risk oncogenic HPV types each year. About 10% of these, or 700,000 are persistent; this is animportant risk factor for cervical dysplasia and invasive cervical cancer. The dynamics of HPV infection and thesubsequent development of high-grade cervical intraepithelial neoplasia are not well understood. Theproposed study will characterize the temporal relationship of vaginal microbiota associated with Metronidazoletreatment of asymptomatic bacterial vaginosis (BV). It will also examine whether Metronidazole treatment ofasymptomatic 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 monthsfrom the BRAVO study, a randomized controlled open labeled clinical trial examining Metronidazole treatmentof asymptomatic BV. The vaginal microbiome will be characterized using high throughput 16s rRNA encodinggene pyrosequencing. The proposed research fits with priorities of the National Cancer Institute (NCI) andNational Institute of Allergy and Infectious Disease (NIAID). NCI has prioritized racial and ethnic disparities inthe incidence and mortality of certain cancers and prevention or early detection of these cancers in specificpopulations and NIAID has set “screening, diagnosis and interventions for target populations to determine howto triage various groups for appropriate prevention, treatment and education strategies” as an overarchingpriority. There are also compelling public health reasons for supporting this application: In spite of theavailability of prophylactic HPV vaccination, there are still more than 528,000 new cases and 266,000 deathsworldwide from cervical cancer related to persistent HPV infections each year. This innovative research willcomplement current HPV vaccine research by providing more data on how the dysbiosis associated with BVallows HPV to bypass vaginal defenses to infect basal epithelial cells—providing information that couldcontribute to more effective vaccines. It also may help inform treatment guidelines. Finally, it will build researchinfrastructure and opportunities for student involvement at the largest minority majority institution in the U.S.
