The Microbiome and Mucosal Immunity in Cervical Cancer Disparities

The microbiome and mucosal immunity in cervical cancer disparities
African American women living in the United States continue to experience an undue higher burden of
cervical cancer and a >2 times higher mortality rate than European American women. This survival disparity
persists after accounting for socioeconomic status and disease stage. The presence of high-risk human
papillomavirus (HPV) is the major cause of cervical cancer and cervical intraepithelial neoplasia. Prophylactic
vaccines are available against the most carcinogenic types and are highly effective, but disparities persist and
the number of people receiving the vaccine remains suboptimal especially for African American women, and the
vaccine is ineffective for the 40% of female US population already infected with genital HPV. Treatment options
for advanced stages are limited, and metastatic cancer is incurable. New therapeutic approaches are therefore
needed but the mucosal mechanisms contributing to disease pathogenesis in African American women are not
well understood. Therefore, identifying mucosal processes and/or mediators which modify HPV persistence vs
clearance and progression vs remission of cervical neoplasia could lead to new or improved treatments and
better CC outcomes for women.
In this proposal we will investigate the contribution of the microbiome and mucosal immunity in the female
genital tract to health disparities in cervical cancer in African American women. This is built upon considerable
data from our lab and others that show that African American women have higher proportion of vaginal microbial
dysbiosis; that vaginal microbial dysbiosis is linked to pro-inflammatory and cancer pathways in cervical mucosa;
that these bacteria produce metabolites that are linked to an immunosuppressive phenotype; that dysbiotic
bacteria can induce cancer pathways in vitro; and cervical cancer tissue gene expression data from African
American women show increased activation inflammatory pathways compared to European American women.
In this concept we will utilize state-of-the-art systems biology techniques, including metagenomics,
metaproteomics, metabolomics, single cell RNA sequencing and flow cytometry to study vaginal mucosal biology
in prospective studies of African American women, coupled with functional studies in PV-associated cervical
cancer mouse models, to better understand these relationships.

Grant Number: 5R01CA266050-04
NIH Institute/Center: NIH
Principal Investigator: Adam Burgener