Abstract PR-14: A synergy between the vaginal microbiome and HPV may have explanatory value for racial disparities in risk of pre-cervical cancer
Authors: Tossas Katherine Y. , Zhao Jinlei , Serrano Myrna , Strauss Jerome , Seewaldt Victoria , Buck Gregory , Winn Robert A. 
Published: January 2022

Abstract
The vaginal microbiome (VMB) is suggested to be a key player in high-risk Human Papilloma Virus (HPV) infection persistence, leading to the development of cervical intraepithelial neoplasia (CIN). While it is generally accepted that the VMB of women with CIN differs from that of healthy women, the VMB composition before a woman develops CIN has not been well studied. Moreover, no studies have evaluated the role of self-reported race on the VMB-CIN relationship, despite reports that the VMB of non-Latina Black (Black) women generally exhibits increased microbial diversity (often associated with HPV tumorigenesis) and lower prevalence of taxa such as Lactobacillus (reported to have an inverse association with severity of cervical abnormalities) compared to their non-Latina White (White) counterparts. Black women have higher HPV prevalence than Whites (39% vs. 24%), and more persistent HPV infections (601 days vs. 316 days, respectively), despite having a similar number of HPV infections to Whites. This suggests that factors beyond multiple HPV exposures sustain the infection. We hypothesize that HPV and the VMB may interact differently by race, to promote development of CIN. Methods: We used 16S-RNA profiles from the VMB of 3,050 consented women visiting the Virginia Commonwealth University clinics for their annual routine exam between August 2009 and November 2013. Of these, 259 had evidence of subsequent CIN after the VMB sample collection, through October 2020. The VMB profiles were characterized into three groups as “Lactobacillus (L) crispatus” group (including L. crispatus, L. gasseri and L. jensenii), “L. iners” group and “Other” based on a priori knowledge of profiled taxa. The “Other” subgroup included taxa, such as G. vaginalis, A vaginae, and others usually associated with bacterial vaginosis-like states. We used self-reported health histories, confirmed by electronic health records to determine HPV status and obtain other socio-demographic information. Multivariable logistic regression models were adjusted for age, smoking, VMB, HPV, marital and pregnancy status. Results: The cohort was mainly Black (70%), and the VMB prevalence by group was 19%, 30% and 51% for L. crispatus, L. iners, and Other, respectively. Twelve percent reported having an HPV diagnosis in the past, and 302 (10%) women developed CIN during an average of 3.6 years of follow-up (259 with CIN 1/2 and 43 with CIN3+). In crude analyses, risk of CIN was 80% higher for Black women (RR=1.8, p&lt;0.0001) compared to Whites. However, a significant interaction between HPV status and the VMB revealed that the risk of a CIN diagnosis for HPV+ Black women with the “Other” VMB subtype, is five-fold (RR=5.3, p&lt;0.40) the risk for Whites. Conclusions: These preliminary results suggest that interactions between the VMB and HPV may account for the differential risk of CIN by race. If replicated in further analyses, VMB profiling could help elucidate the basis of CIN racial disparities.
Citation Format: Katherine Y. Tossas, Jinlei Zhao, Myrna Serrano, Jerome Strauss, Victoria Seewaldt, Gregory Buck, Robert A. Winn. A synergy between the vaginal microbiome and HPV may have explanatory value for racial disparities in risk of pre-cervical cancer [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR-14.