Related Experiment Video
Updated: Jun 25, 2026
Methyl-binding DNA capture Sequencing for Patient Tissues
Published on: October 31, 2016
Clinical validation of a three-marker methylation panel to detect CIN3+ in vaginal self-samples in the Dutch
Jolien de Waard1, Arkajyoti Bhattacharya2, Martine T de Boer1
1Department of Gynecologic Oncology, Cancer Research Center Groningen, University of Groningen, University Medical Center Groningen, PO-box 30.001, 9700 RB, Groningen, The Netherlands.
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
Results:
The three-marker panel showed 73% (298/408) sensitivity and 79% (1640/2071) specificity to detect CIN3+, and identified 96% (21/22) of cervical cancer cases. A scenario analysis was performed on a virtual population of 100 000 hrHPV-positive women using vaginal self-sampling, comparing our methylation triage test with current cytology triage testing. This analysis revealed that more cancers (864 vs. 684 or 770 for 80 or 90% uptake) would be detected with our methylation panel, while referral rates (29% vs. 31% for both 80 and 90% uptake) and detection of CIN3 (72% vs. 68 or 77% for 80 or 90% uptake) would be similar for methylation and cytology.
Conclusion:
Compared to cytology triage testing, DNA methylation triage analysis using our three-marker panel offers an appropriate alternative to detect CIN3+ in hrHPV-positive vaginal self-samples. Implementation of the DNA methylation triage test would not only increase cancer detection, but would also eliminate the need for physician visits for cytological triage testing. In addition, it would accelerate referral decisions, ultimately reducing uncertainty and ensuring timely screening completion for all women.
