Tumor Microbiome Composition in Vaginal and Vulvar Cancers during Chemoradiation

Abstract

<h3>Purpose/Objective(s)</h3> Infection with HPV is associated with vaginal microbiome alterations including higher abundance of Lactobacillus gasseri and Gardnerella vaginalis. Cervical dysbiosis is a risk factor for cervical cancer but less is known about the composition of the tumor microbiome of vaginal and vulvar cancers. In gynecological cancers, surgery, chemotherapy, and radiation are associated with significant shifts in the vaginal microbiome. The purpose of this study is to explore the composition of the tumor microbiome in vaginal and vulvar cancers during and after chemoradiation (CRT) treatment. <h3>Materials/Methods</h3> Tumor swabs from 10 females diagnosed with vulvar (n=3) or vaginal (n=7) cancer were serially collected and analyzed by 16Sv4 rRNA gene sequencing over the course of CRT with four time points collected. Changes in richness by alpha diversity was assessed using paired Wilcoxon signed-rank tests. Linear discriminant analysis effect size (LEfSe) was used to identify distinct taxa that were differentially enriched in baseline samples versus end-of-treatment samples. Principal coordinates analysis (PCoA) analysis using PERMANOVA was used to compare the microbiome of vaginal and vulvar cancer types. Skin toxicity was assessed by searching patients' medical records for clinical findings in the treatment area as well as the use of Mepilex, Nystatin, Diflucan, Antibiotics, and Domeboro recorded during their weekly follow-up appointments. <h3>Results</h3> Wilcoxon signed-rank tests of each time point to baseline sample values did not show statistically significant differences during any of the time points (p>0.05). PCoA pairwise PERMANOVA tests demonstrated statistically significant differences between vaginal and vulvar tumor types (p=0.027). LEfSe demonstrated an increase in relative abundance of taxa Sutterellaceae and Bacteriodia at the end of treatment. Skin toxicity during radiation treatment was present in all vulvar patients and most (71%) vaginal patients but cannot be correlated with microbiome features due to small cohort size. <h3>Conclusion</h3> Our preliminary results demonstrate that richness of vulvar and vaginal samples remained stable during CRT. The microbiome of the tumor microenvironments in vaginal and vulvar samples demonstrated differences in composition. Future studies should be performed to further assess the impact of Sutterellaceae and Bacteriodia on the gynecological microbiota and whether they are associated with increased skin toxicity during CRT treatment.