LAUSR

The vaginal microbiome (VMB) is implicated in the development of high-grade squamous intraepithelial lesions (HSIL). The VMB is taxonomically diverse, immunomodulatory, and racially differentiated. The VMB of Black women exhibits increased microbial diversity (associated with HPV tumorigenesis) and lower prevalence of taxa such as Lactobacillus (inversely associated with severity of cervical abnormalities) compared to white counterparts. Black women also have more persistent HPV infections and higher incidence of HSILs than whites. Our prior publication suggests the relationship between the VMB and HSIL might be differential by self-reported race. Herein we explore the underlying mechanisms by which race may lead to risk of HSIL through the VMB. We used 16S-rRNA VMB taxonomic profiles of 1,168 consented women receiving their annual routine exam between 2009-2013. Of these, 74 (6%) developed HSIL after the VMB sample collection (followed through 10/2020). The VMB profiles were categorized into three subgroups, based on a priori knowledge, by taxonomic abundance as “Lactobacillus crispatus” (including L. crispatus, L. gasseri and L. jensenii, all generally associated with gynecologic health), “L. iners” (considered a transitional state), and “Other” (including taxa, such as Gardenerella vaginalis, Atopibium vaginae, Lachnocurva vaginae and others often associated with adverse gynecologic outcomes). HPV status was obtained by sequencing a fragment of the L1 gene. We used self-reported health histories, confirmed by electronic health records where available, and other socio-demographic information. HIV-positive women were excluded. We used structural equations modeling, following a normal theory maximum likelihood approach with robust errors to estimate the proportion of the association between race and HSIL mediated by the VMB, using STATA version 13.1. The cohort was predominantly Black (72%), with VMB prevalence by subgroup of 18%, 29% and 52% for L. crispatus, L. iners, and Other, respectively. Blacks had a higher prevalence of the “Other” VMB subtype, compared to nL-whites (59% vs. 49%). Forty-five percent of the sample tested positive for HPV, with no significant difference by race (p=0.9). The incidence of HSIL was nearly double for Blacks compared to whites (7% to 4%). Women with HSIL exhibited a higher prevalence of the “Other” VMB (68% vs. 51%) and were more likely to be HPV positive (73%vs. 44%) than their healthy counterparts. In SEM, only the following path was statistically significant at p<0.05: raceàVMBàHSIL, with an estimated proportion mediated by this path of 36%. Findings suggest the VMB is a mediator that might explain some of the underlying mechanisms of the relationship between race and risk of HSIL. If confirmed, this might have potential prophylactic and therapeutic implications as the VMB is amenable to pre and probiotics. Citation Format: Katherine Y. Tossas, Stephanie Sullivan, Myrna Serrano, Jerome Strauss, Robert A. Winn, Gregory Buck. The vaginal microbiome as a mediator in the relationship between Black/White race and high grade cervical intraepithelial neoplasia. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5771.