Abstract

Abstract Background: Women with gynecological cancer (GynCa) undergoing radiation therapy (RT) are at increased risk for acute and long-term sexual dysfunction after treatment. The vaginal microbiome (VM) is the first line of defense against vaginal infection and sexually transmitted diseases. Compositions of VM between women with GynCa receiving RT and healthy women and associations between the VM and sexual dysfunction and vaginal adverse events are unknown. Methods: Using a longitudinal study design, VM, patient-reported sexual dysfunction and physician-reported vaginal adverse events data were collected from postmenopausal GynCa women receiving RT and healthy postmenopausal women. VM swabs from mid-vagina were used for DNA extraction and sequencing of the V3-V4 region of the 16S rRNA gene. Female Sexual Function Index (FSFI) was used to measure women's sexual dysfunction; the Common Terminology Criteria for Adverse Event (CTCAE) Reporting System was used to assess the severity of vaginal adverse events by physicians. All data were collected pre-RT, right after RT completion, 6- and 12-months post-RT. Group-based trajectory modeling was used to identify the sexual dysfunction trajectories. VM compositions were obtained using Qiime and associations with sexual dysfunction trajectories and vaginal adverse events were identified with univariate and multivariate analysis of variance in the R package vegan. Bacterial taxa characteristic for each trajectory group were identified using the LefSe pipeline. Results: Sixty-five patients with GynCa receiving RT and 69 healthy women participated. GynCa and healthy groups had no differences in age and race. VM communities were dominated by Lactobacillus, Prevotella, Dialister and Anaerococcus bacterial genera. We observed higher α-diversity in cancer than healthy patients, and in post-RT VMs than pre-RT. Three groups of sexual dysfunction trajectories were identified: low risk (17.4%), moderate risk (12.3%), and high risk (70.4%). Cancer and healthy women had no difference in sexual dysfunction trajectories. The VM compositions (Bray-Curtis Index) showed significant or marginal associations with vaginal pH (p=0.001), FSFI total score (p=0.001), all domains of FSFI (desire, arousal, lubrication, orgasm, pain, and satisfaction, all p<0.05); CTCAE of vaginal pain (p=0.054), hemorrhage (p=0.004), and inflammation (p=0.071). VM pre-RT predicted the trajectories of arousal (p=0.009), lubrication (p=0.009), and pain (p=0.043). Specific bacterial taxa were enriched in the groups of high risk sexual dysfunction (3 taxa for arousal; 12 taxa for lubrication; 3 taxa for vaginal pain) as compared to low or moderate risk groups. Peptoniphilus, Anaerococcus, and Actinotignum genera were associated with all high risk groups for arousal, lubrication, and pain. Conclusions: Significant associations between VM and sexual dysfunction and vaginal adverse events were found for women with GynCa undergoing RT. Infection-related genera such as Peptoniphilus, Anaerococcus, and Actinotignum genera were enriched in women with high risk of sexual dysfunction. Future research should explore the VM function in the sexual dysfunction and vaginal adverse events in this population. Citation Format: Jinbing Bai, Despina Tsementzi, Pretesh Patel, Joseph Shelton, Mary Dolan, Jessica Arluck, Namita Khanna, Tony Y. Eng, Konstantinos T. Konstantinidis, Deborah Watkins Bruner. Vaginal microbiome associated with patient-reported sexual dysfunction and physician-reported vaginal adverse events in gynecologic cancer women across radiotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-362.

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