Microbes of the female genital tract, inflammation and ovarian cancer

Abstract

Background: Eighty-five percent of cases of ovarian cancer are sporadic and the mechanisms behind ovarian oncogenesis are unclear. Several putative modifiable risk factors have been suggested but robust evidence is lacking. Exploratory studies in ovarian cancer have demonstrated cervicovaginal dysbiosis both in women with ovarian cancer and those at risk of ovarian cancer e.g., carrying BRCA mutation.

Aims: The first aim was to critically appraise the strength of epidemiological evidence for associations between non-genetic risk factors and ovarian cancer. The second aim was to investigate if genuine bacterial signals from low bacterial biomass sites of the upper genital tract can be detected above background contaminants and if so, establish whether a bacterial continuum is present along throughout the genital tract of ovarian cancer patients and patients with benign pathology. The third aim was to test the hypothesis that ovarian cancer patients harbour a distinctive bacterial fingerprint in their genital tract compared to benign controls.

Results: An umbrella review of the literature identified six associations graded with strong evidence which increased the risk of developing ovarian cancer, and one which reduced the risk. Metataxonomic profiling of bacterial communities of the reproductive tract of ovarian cancer (n=19) and control patients (n=12) along with controls indicated that approximately 20% of recovered sequencing data could be attributed to contamination. Cervicovaginal dysbiosis was more prevalent in the ovarian cancer cohort. The benign cohort all demonstrated a continuum of bacterial species with a similar trend noted in 80% of malignant patients. Differentially abundant taxa were identified at all reproductive tract sites when comparing the benign and malignant cohorts.

Discussion: The results of this descriptive exploratory study contributes to the hypothesis that the bacterial signature of the female genital tract may play a role in ovarian oncogenesis and warrants extensive, systematic investigation to further explore host-microbiome interactions.