Abstract 1360: DNA methylation analysis in self-sampled material as a triage test in hrHPV positive women

Background: Primary hrHPV testing in cervical cancer screening shows relatively low specificity. To decrease the number of unnecessary referrals for colposcopy, triage testing is necessary. In this study, DNA methylation analysis was compared with routine cytology for triage testing in hrHPV positive women. Moreover, feasibility of DNA methylation analysis directly on original brush-based self-sampled specimens was assessed. Methods: Non-responding women from population-based screening were invited to self-collect a cervico-vaginal specimen for hrHPV testing; hrHPV positive women were referred to a physician for liquid-based sampling. For this pilot study, DNA methylation analysis was performed on 128 triage samples and on 50 matched Evalyn brush self-samples with QMSP for C13ORF18, EPB41L3, JAM3 and TERT. Results: In the physician-taken triage material, DNA methylation analysis of JAM3 showed the highest specificity (88%) combined with a high sensitivity (82%) for detection of CIN3+, whereas cytology showed a specificity of 48% and a sensitivity of 91%. Out of 39 women with abnormal cytology and normal histology (false positive by cytology), 87% were negative for JAM3 and 90% for C13ORF18 methylation. The agreement for DNA methylation analysis performed directly on the matched self-sampled material and the physician-taken samples was 90% for C13ORF18 (κ=0.77; p Conclusion: DNA methylation analysis as a triage test in hrHPV positive women outperformed cytology due to higher specificity without losing its sensitivity and is also feasible to be performed directly on Evalyn Brush self-samplers. This might result in more correct referrals to the gynecologist and eliminate the need for a new scraping taken by a medical professional thereby offering great logistic and financial advantages. This study was financed by the Dutch Cancer Society (RUG-NKB2009-4577). Citation Format: Aniek Boers, Remko P. Bosgraaf, Roland W. van Leeuwen, Ed Schuuring, Leon FAG Massuger, Johan Bulten, Willem JG Melchers, Ate GJ van der Zee, Ruud LM Bekkers, Bea Wisman. DNA methylation analysis in self-sampled material as a triage test in hrHPV positive women. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1360. doi:10.1158/1538-7445.AM2014-1360