| Avtor/Urednik | Leeuwen, Robert W.; Oštrbenk, Anja; Poljak, Mario; Zee, Ate G. J.; Schuuring, Ed; Wisman, Bea A. | |
| Naslov | DNA methylation markers as a triage test for identification of cervical lesions in a high risk human papillomavirus positive screening cohort | |
| Tip | članek | |
| Vol. in št. | Letnik 144, št. 4 | |
| Leto izdaje | 2019 | |
| Obseg | str. 746-754 | |
| ISSN | 0020-7136 - International journal of cancer : Journal international du cancer | |
| Jezik | eng | |
| Abstrakt | Objective triage strategies are required to prevent unnecessary referrals for colposcopy in population-based screening programs using primary high-risk human papillomavirus (hrHPV) testing. We have identified several DNA methylation markers with high sensitivity and specificity for detection of high-grade cervical intraepithelial neoplasia or worse (CIN2+) in women referred for colposcopy. Our study assessed diagnostic potential of these methylation markers in a hrHPV-positive screening cohort. All six markers (JAM3, EPB41L3, C13orf18, ANKRD18CP, ZSCAN1 and SOX1) showed similar association across histology in the hrHPV-positive cohort when compared to the Dutch cohort (each p > 0.15). Sensitivity for CIN2+ was higher using methylation panel C13orf18/EPB41L3/JAM3 compared to the other 2 panels (80% vs. 60% (ANKRD18CP/C13orf18/JAM3) and 63% (SOX1/ZSCAN1), p = 0.01). For CIN3+ all three methylation panels showed comparable sensitivity ranging from 68% (13/19) to 95% (18/19). Specificity of SOX1/ZSCAN1 panel (84%, 167/200) was considerably higher compared to ANKRD18CP/C13orf18/JAM3 (68%, 136/200, p = 2 X 10-5) and C13orf18/EPB41L3/JAM3 (66%, 132/200, p = 2 X 10-7). High negative predictive value (NPV) (91-95% and 96-99%) was observed for CIN2+ and CIN3+, for all three methylation panels, while positive predictive value (PPV) varied from 25 to 40% for CIN2+ and 15-27% for CIN3+. Interestingly, 118/235 samples were negative for all six markers (including 106 controls (89.8%), 6 CIN1 (5.1%), 5 CIN2 (4.2%) and 1 CIN3 (0.8%)). Methylation results from both independent cohorts were comparable as well as high sensitivity for detection of cervical cancer and its high-grade precursors in hrHPV-positive population. Our study therefore validates these methylation marker panels as triage test either in hrHPV-based or abnormal cytology-based screening programs. | |
| Proste vsebinske oznake | (pred) maligni rak materničnega vratu markerji DNA metilacije odkrivanje raka materničnega vratu (pre)malignant cervical cancer DNA methylation markers cervical cancer screening |