Do Cervicovaginal Microbiota Play a Role in Ovarian Cancer Formation?

A lower percentage of certain kinds of cervicovaginal bacteria are associated with having ovarian cancer or risk factors for the malignancy, according to a new study published in Lancet Oncology.

“Evidence is accumulating that microbiota can affect the risk of cancer development, response to oncological therapy, and development of cancer-associated and treatment-related complications,” wrote study authors led by Nuno R. Nené, PhD, of University College London.

Much of this accumulating data centers around the gut microbiome, Nené said, but there are some data suggesting a role for urinary and cervicovaginal microbiomes as well.

Researchers studied whether ovarian cancer may be associated with imbalances in the cervicovaginal microbiome. The bacteria are essential in generating a protective low vaginal pH.            

The study included two cohorts. The ovarian cancer cohort included 360 women (176 with ovarian cancer, 115 healthy controls, and 69 controls with benign gynecological conditions); the BRCA cohort included 220 women (109 with BRCA1 mutations, 97 healthy controls wild-type for both BRCA1 and BRCA2, and 14 controls with a benign condition wild-type for the two BRCA genes).

Cervicovaginal samples were gathered from all women and sequenced using 16S rRNA sequencing; researchers calculated the proportion of lactobacilli species (Lactobacillus crispatus, Lactobacillus iners, Lactobacillus gasseri, and Lactobacillus jensenii), which they describe as being essential for the generation of a “protective low vaginal pH.” When lactobacilli accounted for at least 50% of the present species, this was considered community type L; when they accounted for less than 50% of species, this was considered community type O.

In the ovarian cancer cohort, among women younger than 50 years, those with ovarian cancer had a significantly higher prevalence of community type O bacteria compared to age-matched controls, with an odds ratio of 2.80 (95% CI, 1.17–6.94; P = 0.020).

Similarly, in the BRCA cohort, those under the age of 50 years with BRCA1 mutations were more likely to have community type O bacteria than age-matched controls, with an OR of 2.79 (95% CI, 1.25–6.68; P = 0.012); this was calculated after an adjustment for ever having been pregnant. The risk was increased among women with at least one first-degree family member affected by any cancer, with an OR of 5.26 (95% CI, 1.83–15.30; P = 0.0022).

When restricted to even younger patients, the associations between community type O bacteria and cancer or BRCA mutations was even stronger. The OR for type O in the ovarian cancer set specifically among those under the age of 40 years was 7.00 (95% CI, 1.27–51.44; P = 0.025).

The authors noted that before any clinical trials using this information are initiated, the findings need to be validated.

“The application of vaginal suppositories containing a combination of live lactobacilli and oestriol normalises the vaginal microbiota,” they wrote “Establishing whether a continuous community type L cervicovaginal microbiome could reduce the risk of ovarian cancer should be a priority for further studies in this area.”

In an accompanying editorial, Hans Verstraelen, MD, PhD, MPH, of Ghent University in Belgium, called the findings “highly novel,” but noted that they raise the question of a specific mechanism linking vaginal microbiota to ovarian neoplasia. Though a number of potential mechanisms exist, “these findings underline the need for systems biology approaches in ovarian cancer research,” rather than presenting a case for probiotic treatment approaches.

“Overall, there is no direct evidence that the human microbiota has a key role in cancer causation, but the microbiota needs to be taken into account in future research,” Verstraelen wrote.