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Type O Cervicovaginal Microbiota Linked to Higher Risk for Ovarian Cancer

 Findings from a recent study show that ovarian cancer is significantly associated with having a community type O cervicovaginal microbiota (Lancet Oncol. 2019;20[8]:1171-1182).

“Various factors-including age, family history, inflammation, reproductive factors, and tubal ligation-modulate the risk of ovarian cancer,” said Nuno R. Nené, PhD, Department of Women's Cancer, EGA Institute for Women's Health, Faculty of Population Health Sciences, University College London, United Kingdom, and colleagues.

“In this study, our aim was to establish whether women with, or at risk of developing, ovarian cancer have an imbalanced cervicovaginal microbiome,” they continued.

Between January 2, 2016, and July 21, 2018, the investigators recruited 2 sets of women from across the Czech Republic, Germany, Italy, Norway, and the United Kingdom for inclusion in the trial, which evaluated the adjusted relationship between BRCA1 status and ovarian cancer status and cervicovaginal microbiota community type.

The ovarian cancer set (n = 360) included 176 women with epithelial ovarian cancer, 115 healthy controls, and 69 controls with benign gynecological conditions. The BRCA set (n = 220) included 109 women with BRCA1 mutations, 97 healthy controls wild type for BRCA1 and BRCA2, and 14 controls with a benign gynecological condition wild type for BRCA1 and BRCA2.

Using the ThinPrep system cervicovaginal samples were gathered from all patients for 16S rRNA gene sequencing.

“For each sample, we calculated the proportion of lactobacilli species (ie, Lactobacillus crispatus, Lactobacillus iners, Lactobacillus gasseri, and Lactobacillus jensenii), which are essential for the generation of a protective low vaginal pH, in the cervicovaginal microbiota,” Dr Nené and colleagues explained.

“We grouped samples into those in which lactobacilli accounted for at least 50% of the species present (community type L) and those in which lactobacilli accounted for less than 50% of the species present (community type O),” they added.

Patients were divided into 1 of 2 cohorts based on whether they were aged <50 years or ≥50 years. A higher prevalence of community type O microbiota was observed in women aged ≥50 years (81 [61%] of 133 ovarian cancer cases and 84 [59%] of 142 healthy controls) versus <50 years (23 [53%] of 43 cases and 12 [29%] of 42 controls).

In addition, women in the ovarian cancer set aged <50 years had a significantly higher prevalence of community type O microbiota than age-matched controls under a logistic regression model with bias correction (odds ratio [OR], 2.80; 95% CI, 1.17-6.94; P = .020).

Among patients in the BRCA set, those with BRCA1 mutations aged <50 years were more likely to have community type O microbiota than age-matched controls (OR, 2.79; 95% CI, 1.25-6.68; P = .012) after being adjusted for any history of pregnancy. This risk was increased among patients with >1 first-degree family member with any type of cancer (OR, 5.26; 95% CI, 1.83-15.30; P = .0022).

Of note, across patients in both study sets, younger age was tied to a stronger association between community type O microbiota and ovarian cancer or BRCA1 mutation status.

“The presence of ovarian cancer, or factors known to affect risk for the disease (ie, age and BRCA1 germline mutations), were significantly associated with having a community type O cervicovaginal microbiota,” Dr Nené and colleagues said.

“Whether re-instatement of a community type L microbiome by using, for example, vaginal suppositories containing live lactobacilli, would alter the microbiomial composition higher up in the female genital tract and in the fallopian tubes…, and whether such changes could translate into a reduced incidence of ovarian cancer, needs to be investigated,” they concluded.—Hina Khaliq

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