Somatic mutations in cervicovaginal samples: assessing their role in ovarian cancer detection and prognosis

BACKGROUND: Most patients with ovarian cancer are diagnosed at a late stage because of the lack of early stage symptoms or effective screening methods. To address this issue, we evaluated the presence of DNA somatic variants in cervicovaginal samples to aid the detection and prognosis of ovarian cancer. METHODS: We employed next-generation sequencing (NGS) with molecular identifiers to analyze samples from a case-control study involving women diagnosed with ovarian cancer and age-matched controls. The study included Pap smear samples from 43 patients with ovarian cancer and 99 controls, 27 paired vaginal self-samples, 16 endometrial aspirates, and 13 tumor samples from cases, for a total of 198 samples. RESULTS: Pathogenic and likely pathogenic variants were identified in 25.6 % (11/43, 95 % confidence interval -CI-:13.5-41.2) of Pap smear samples from patients with ovarian cancer. These variants were also found in 33.3 % of the control samples, leading to a specificity of 66.7 % (66/99, 95 %CI:56.5-75.8 %). Among the paired samples, we observed pathogenic and likely pathogenic variants in 14.3 % (2/14, 95 %CI:1.78-42.8) of the vaginal samples, 77.8 % (7/9, 95 %CI:40.0-97.2) of the endometrial aspirates, and 69.2 % (9/13, 95 %CI:39.6-90.9) of the tumor samples. In the age- and stage-adjusted survival models, women with variants detected in Pap smear samples had poorer overall survival than those without variants (hazard ratio -HR-=4.27, 95 %CI:1.06-17.23; P = 0.041). CONCLUSIONS: DNA somatic variants in cervicovaginal samples have limited diagnostic value for detecting ovarian cancer. However, their presence may have prognostic significance, warranting further investigation. Future research could explore multimodal strategies that integrate molecular markers with imaging or other approaches to improve early detection.