Screening for Ovarian Cancer in the General Population: State of Art and Perspectives of Clinical Research

Background/Aim: Screening for ovarian cancer in the general population is a challenging issue. The aim of this review was to analyze both the studies based on serum CA125 assay and ultrasound (US) and the novel perspectives of clinical and biological research on this issue. Materials and Methods: The trials on the combination of serum CA125 and vaginal/ pelvic US as well as the investigations on microRNA (miRNA)s, circulating tumor DNA and tumor protein 53 (TP53) variants in DNA purified from Pap smears have been critically analyzed. Results: Two large randomized trials failed to detect a reduction in ovarian cancer-related deaths in women who underwent serum CA125-and US-based screening compared to those who had no screening. The United Kingdom Collaborative Trial of Ovarian Cancer Screening reported a 39.2% higher incidence of stage I-II and 10.2% lower incidence of stage III-IV disease in women who underwent annual multimodal screening with serum CA125 and vaginal US compared to women who had no screening, but this stage shifting did not translate into a survival benefit. A longitudinal, multiple biomarker algorithm-based strategy might improve ovarian cancer detection compared with serial CA125 alone. The use of serum tumor-associated autoantibodies, circulating tumor DNA and microRNA is still investigational. The identification of TP53 clonal variants in DNA purified from Pap smears can detect early steps of serous ovarian carcinogenesis. Conclusion: The availability of sensitive next-generation sequencing-based approaches for TP53 assessment in PAP smears may allow the reliability of this genetic marker for early detection of ovarian cancer to be verified.