Clinical validation of a three-marker methylation panel to detect CIN3+ in vaginal self-samples in the Dutch population-based screening programme

Abstract

Background: The use of vaginal self-sampling for cervical cancer screening is promising and increasing. However, triage cytology cannot be performed on vaginal self-sampling material after a high-risk human papilloma virus (hrHPV)-positive result. In our recent discovery study, we identified a three-marker panel with high sensitivity (82%) and specificity (74%) for CIN3 or worse (CIN3+). In the present study, we performed the clinical validation of this three-marker panel using real-world hrHPV-positive vaginal self-samples obtained through the Dutch screening programme. Methods: The markers LHX8, EPB41L3 and ANKRD18CP were analysed using quantitative methylation-specific PCR (QMSP) on a consecutive cohort of hrHPV-positive vaginal self-samples (n = 2482: 408 CIN3+ and 2074