Carlos Salomón, Melissa Razo-Azamar, A Gentry-Maharaj, Gregory E. Rice, Usha Menon
INTRODUCTION: Ovarian cancer is a leading cause of cancer-related death in women, primarily due to nonspecific symptoms and diagnosis at an advanced stage. Improving outcomes through earlier diagnosis and effective population screening remains a global priority. CONTEXT: Existing modalities ,including CA125 and transvaginal ultrasound (TVUS), lack sufficient specificity and sensitivity, and no screening strategy has demonstrated a reduction in mortality. Multivariate Index Assays (MIAs), that combine multiple biomarker results into a single risk score, have emerged as a promising approach for differential diagnosis of adnexal masses, early detection, and screening. AREAS COVERED: This review summarizes current literature and clinical trial data on MIAs in ovarian cancer, describing their advantages over single biomarkers, their potential to improve patient outcomes, and their role in personalized medicin. Successful clinical adoption of MIAs will depend on well-designed prospective studies that robustly validate their clinical utility. EXPERT OPINION/COMMENTARY: It is also critical to clearly distinguish between diagnostic and screening applications, as each requires different performance characteristics, regulatory pathways, and target populations, and no ovarian cancer screening test is currently approved for routine use.