Diagnostic accuracy of cytology for the detection of endometrial cancer in urine and vaginal samples

Abstract

Postmenopausal bleeding triggers urgent investigation by sequential invasive tests that are avoidable for the 90-95% of women who do not have endometrial cancer. A simple, non-invasive tool that accurately identifies cancer and safely reassures healthy women could transform patient care. Here we report, in a cross-sectional diagnostic accuracy study of 103 women with known cancer and 113 with unexplained postmenopausal bleeding, that urine and vaginal cytology has a combined sensitivity of 91.7% (95% CI 85.0%, 96.1%) and specificity of 88.8% (81.2%, 94.1%) for gynecological cancer detection. Cytology identifies 91 endometrial, two fallopian tube and one cervical cancer from 103 known cancer cases. In women with unexplained postmenopausal bleeding, cytology identifies all four endometrial cancers and three others (cervical, ovarian and bladder), for a 12/107 (11.2%) false positive rate. We show proof-of-principle that endometrial cancer can be detected in urine and vaginal fluid. Prospective validation of these findings will support incorporation of this non-invasive test into clinical practice.

Fig. 1. STARD diagram showing flow of participants through the study.

Key. ET, endometrial thickness; ET <4 mm, histology not indicated; EC, endometrial cancer; PMB, postmenopausal bleeding. *Other cancers: ovarian (n = 1), fallopian tube (n = 2), cervical (n = 2). Cytology scoring: positive (vaginal and/or urine cytology positive); negative (both vaginal and urine cytology negative); inconclusive (both vaginal and urine cytology inadequate for assessment).

Fig. 2. Photomicrograph showing morphology and immunohistochemistry profile of endometrial cancer cells in urogenital samples.

a Urine sample showing positive urine cytology (SurePath), demonstrating a single cluster of endometrial cells with malignant features, including enlarged hyperchromatic nuclei, coarse chromatin, prominent nucleoli, irregular nuclear outlines and high nuclear-to-cytoplasmic ratio. b–f Vaginal sample demonstrating the immunoprofile of these cells, consistent with epithelial cells from the female genital tract, CK7+ (b), CK20− (c), ER+ (d), PAX8+ (e), GATA3− (f). Scale bar = 100 μm.