The best way to reduce the risk of dying from cancer is early detection and diagnosis. For cancers like colon and breast cancers, screening can often detect disease before perceivable symptoms, which often portend advanced cancer and hence a worse prognosis. However, many cancers do not have reliable screening methods, including ovarian cancer, one of the most lethal gynecologic cancers. Even when ovarian cancer becomes symptomatic, the symptoms are nonspecific, which often causes further delays in diagnosis. Indeed, most ovarian cancer is not diagnosed until stage III (when it has invaded the abdominal cavity) or stage IV (when it has become metastatic and spread to distant organs), at which point the five-year survival rate is less than 30%. In contrast, the five-year survival rate for stage I ovarian cancer is above 90%.
Clinical trials have tested whether modalities typically used to make ovarian cancer diagnoses (e.g., plasma biomarker cancer antigen 125, either alone or combined with transvaginal ultrasounds) could be used for screening, but these tests were not sufficiently sensitive to early-stage disease.1,2 Since earlier detection is crucial for improving ovarian cancer prognosis, a proof-of-principle study recently explored whether high-grade ovarian cancer could be detected years earlier by analyzing the DNA from cervical cancer screening Papanicolaou (Pap) tests.3 (Brace yourselves – we’re about to dive into some technical details of cancer development and screening test performance metrics. For a little more background in these areas, see AMA #56.)
Previous trials that used modalities typically used to make ovarian cancer diagnoses have failed to reduce ovarian cancer mortality because the methods of detection were not sensitive enough to early-stage disease.1,2 By contrast, the genomic analyses employed in this study were able to detect cancerous changes nearly a decade before diagnosis – an enormous advantage in combating a disease for which the five-year survival rate at stage I is over three times higher than the survival rate at stage IV. Since the DNA analysis can be done on samples that are already routinely collected for cervical cancer screening, this may be a feasible way to add ovarian cancer screening to the current standard of care in populations most vulnerable to this type of cancer. While the test, as it currently stands, is far too susceptible to false positives to justify use in the general female population of average ovarian cancer risk, its use as a screening method for women with especially high baseline risk has the potential to improve clinical outcomes associated with this disease.
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