{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:27:58Z","timestamp":1791959278007,"version":"4.3.4"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,10,31]],"date-time":"2018-10-31T00:00:00Z","timestamp":1540944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["RUG\u2010NKB2009\u20104577"],"award-info":[{"award-number":["RUG\u2010NKB2009\u20104577"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2019,2,15]]},"abstract":"<jats:p>Objective triage strategies are required to prevent unnecessary referrals for colposcopy in population\u2010based screening programs using primary high\u2010risk human papillomavirus (hrHPV) testing. We have identified several DNA methylation markers with high sensitivity and specificity for detection of high\u2010grade cervical intraepithelial neoplasia or worse (CIN2+) in women referred for colposcopy. Our study assessed diagnostic potential of these methylation markers in a hrHPV\u2010positive screening cohort. All six markers (<jats:italic>JAM3<\/jats:italic>, <jats:italic>EPB41L3<\/jats:italic>, <jats:italic>C13orf18<\/jats:italic>, <jats:italic>ANKRD18CP<\/jats:italic>, <jats:italic>ZSCAN1<\/jats:italic> and <jats:italic>SOX1<\/jats:italic>) showed similar association across histology in the hrHPV\u2010positive cohort when compared to the Dutch cohort (each <jats:italic>p<\/jats:italic> &gt; 0.15). Sensitivity for CIN2+ was higher using methylation panel <jats:italic>C13orf18\/EPB41L3\/JAM3<\/jats:italic> compared to the other 2 panels (80% <jats:italic>vs<\/jats:italic>. 60% (<jats:italic>ANKRD18CP\/C13orf18\/JAM3<\/jats:italic>) and 63% (<jats:italic>SOX1\/ZSCAN1<\/jats:italic>), <jats:italic>p<\/jats:italic> = 0.01). For CIN3+ all three methylation panels showed comparable sensitivity ranging from 68% (13\/19) to 95% (18\/19). Specificity of <jats:italic>SOX1\/ZSCAN1<\/jats:italic> panel (84%, 167\/200) was considerably higher compared to <jats:italic>ANKRD18CP\/C13orf18\/JAM3<\/jats:italic> (68%, 136\/200, <jats:italic>p<\/jats:italic> = 2 \u00d7 10<jats:sup>\u22125<\/jats:sup>) and <jats:italic>C13orf18\/EPB41L3\/JAM3<\/jats:italic> (66%, 132\/200, <jats:italic>p<\/jats:italic> = 2 \u00d7 10<jats:sup>\u22127<\/jats:sup>). High negative predictive value (NPV) (91\u201395% and 96\u201399%) 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\u201327% 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\u2010grade precursors in hrHPV\u2010positive population. Our study therefore validates these methylation marker panels as triage test either in hrHPV\u2010based or abnormal cytology\u2010based screening programs.<\/jats:p>","DOI":"10.1002\/ijc.31897","type":"journal-article","created":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T11:16:26Z","timestamp":1538046986000},"page":"746-754","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["DNA methylation markers as a triage test for identification of cervical lesions in a high risk human papillomavirus positive screening cohort"],"prefix":"10.1002","volume":"144","author":[{"given":"Robert W.","family":"van Leeuwen","sequence":"first","affiliation":[{"name":"Department of Gynaecologic Oncology Cancer Research Centre Groningen, University of Groningen, University Medical Centre Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"O\u0161trbenk","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Immunology Faculty of Medicine, University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Poljak","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Immunology Faculty of Medicine, University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ate G. J.","family":"van der Zee","sequence":"additional","affiliation":[{"name":"Department of Gynaecologic Oncology Cancer Research Centre Groningen, University of Groningen, University Medical Centre Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ed","family":"Schuuring","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Research Centre Groningen, University of Groningen, University Medical Centre Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4830-3401","authenticated-orcid":false,"given":"G. 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