The dire need to develop a clinically validated screening method for the detection of early-stage ovarian cancer

For almost half a century, the WHO has urged the medical community to create screening methods with the primary purpose of detecting disease at an early, treatable stage [1]. This is of particular importance in epithelial ovarian cancer (EOC) given that there are no clinically validated biomarkers or screening protocols available for the accurate detection of early-stage disease. This year, approximately 22,000 women will be newly diagnosed with ovarian cancer, while an additional 15,000 deaths will be attributed to this disease [2]. These statistics make EOC the fifth leading cause of cancer death in women and the most lethal gynecologic malignancy, with more women dying from this disease than all other gynecologic malignancies combined [2]. In addition, during the past 40 years, the overall survival for women with advanced-stage (III/IV) EOC has remained relatively unchanged, at less than 30%, despite surgical advancements and improvements in chemo therapeutics [2]. However, women diagnosed with early-stage EOC (stage I) require less morbid surgical procedures, may not require adjuvant chemotherapy, have an improved quality of life and, most importantly, have an overall survival approaching 93% [2]. Unfortunately, the majority of women (75%) continue to be diagnosed with advanced-stage EOC owing to the rather stealth nature of early-stage disease and the lack of a clinically validated screening method. Therefore, increasing the proportion of women detected with early-stage EOC, particularly stage I, would significantly improve women’s healthcare. The standard screening methods currently in use to detect ovarian cancer include pelvic exams, transvaginal or transabdominal ultrasonography and the serum cancer antigen (CA)125 level. Quantitative CA125 levels have long been the ‘gold standard’ biomarker test for the surveillance of women with EOC; however, it is only elevated in 47% of women with early-stage disease. Moreover, CA125 is nonspecific and is elevated in many disease states, such as other abdominal malignancies, benign diseases and physio logical conditions. Therefore, its effectiveness as an independent screening test is compromised owing to its lack of sensitivity and specificity. Although many other tumor biomarkers have been identified in ovarian cancer during the past decade, few of them have been widely tested for screening purposes. Furthermore, traditional ultra sonography is not an effective population screening test owing to its rather low sensitivity and specificity, both alone and combined with CA125. Given ovarian cancer’s relatively low general population incidence rate (1.8%) [2], a valid screening test must have both a high sensitivity and a high specificity to decrease the number of false-positive test results and the subsequent invasive surgical procedures undoubtedly associated with this result. The ideal screening test for the postmenopausal population (with a prevalence of one in 2500) would require a specificity of 99.6% to yield an approximate positive predictive value of 10%, where a surgeon performs ten operations for each case of ovarian cancer detected. The positive predictive value of most screening tests is determined by specificity and disease incidence – given ovarian cancer’s low frequency, achieving an acceptable positive predictive value requires an extremely high specificity, especially in average-risk populations. Multiple initiatives have been undertaken to discover strategies that detect and diagnose early-stage EOC, including the search for novel serum biomarkers and the development of new technologies, such as contrast-enhanced ultrasonography, with a number of them demonstrating hopeful results. The ideal screening test for ovarian cancer would be a simple measurement of biomolecules in bodily fluids, such as blood,