Niche homology of the cervicovaginal microbiome and its association with the outcome after chemoradiotherapy in cervical carcinoma patients

Abstract

Background: The microbiome within tumors can influence treatment response in cancer. In cervical carcinoma, relationships among the vaginal and tumor microbiomes and response to chemoradiotherapy are unclear. We sought to determine if the niche homology and specific signatures of cervicovaginal microbiome are associated with the outcome of chemoradiotherapy in cervical carcinoma patients. Methods: Sixty-eight women with cervical carcinoma were enrolled, and intratumoral or vaginal samples and peripheral blood samples were collected one week before chemoradiotherapy. DNA was extracted from tumor tissue biopsy and vaginal swab samples, and V3 and V4 variable regions of the 16S rRNA gene were amplified by PCR. Levels of blood immunomodulatory proteins were measured with a Millipore HCKPMAG-11K kit and Luminex 200 platform (Luminex, USA). Results: We found abundance to be higher in the tumor, and the homology between vaginal and tumor microbiota was associated with response to chemoradiotherapy. The proportion of the microbiome originating from the vagina and appearing in the tumor was higher among poor-responders than among good-responders. Amplicon sequence variants (ASVs) were located in both tumors and vagina correlated with TNM disease stage, human papillomavirus (HPV) infection (high- vs low-risk), metastasis (yes/no), and immune checkpoint proteins. The proportion of two microbes from the shared cervicovaginal ASVs, g_Sphingobium_s_Sphingobium_xenophagum_333 in tumor and g_Ralstonia_256 in vagina, could predict response to chemoradiotherapy (AUC=0.984, AUPR=0.917). Conclusion: Our results suggest that microbiome components co-located in the vagina and in cervical tumors may be useful biomarkers to predict response to chemoradiotherapy for cervical carcinoma.