Protein signatures for the early detection of endometrial cancer in cervico-vaginal fluid

INTRODUCTION: Endometrial cancer is the most common gynecological malignancy in high-income countries. Although postmenopausal bleeding is its cardinal presenting symptom, only 5-10% of women with postmenopausal bleeding have malignancy. There is therefore a need for accurate, minimally invasive diagnostic tests. Proteins detectable in proximal biofluids, particularly cervicovaginal fluid (CVF), represent promising biomarkers because they reflect the functional biology of the tumor and can be measured using clinically translatable immunoassays. AREAS COVERED: This review critically evaluates the evidence for CVF protein biomarkers in the early detection of endometrial cancer. Three protein signatures show the greatest promise: a five-protein panel (HPT, LGALS3BP, FGA, LY6D, IGHM; AUC 0.95), a 12-protein inflammatory panel (AUC 0.91), and an 11-protein multivariate panel (AUC 0.92), all approaching or meeting thresholds for clinical consideration. We also discuss the biological relevance of these proteins and highlight the methodological, analytical and translational challenges that must be addressed before clinical implementation. EXPERT OPINION: CVF provides a unique, minimally invasive sampling medium owing to the anatomical continuity between the uterine cavity and lower genital tract. While current evidence is encouraging, most candidate biomarkers remain exploratory and require rigorous validation in large, prospective multicentre studies before incorporation into routine clinical practice.