{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:27:53Z","timestamp":1791959273694,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,1,28]],"date-time":"2014-01-28T00:00:00Z","timestamp":1390867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2014,8,15]]},"abstract":"<jats:p>Methylation markers were studied for their suitability to triage human papillomavirus (HPV)\u2010positive women by testing self\u2010collected cervico\u2010vaginal lavage specimens. For this purpose, we analyzed 355 hrHPV\u2010positive self\u2010collected specimens with three methylation markers, that is, <jats:italic>CADM1<\/jats:italic>\u2010m18, <jats:italic>MAL<\/jats:italic>\u2010m1 and <jats:italic>miR\u2010124<\/jats:italic>\u20102 by quantitative methylation\u2010specific PCR. The areas under the receiver\u2010operating characteristic (ROC) curve for end\u2010point cervical intraepithelial neoplasia grade 3 or worse (CIN3+) were 0.637 for <jats:italic>CADM1<\/jats:italic>\u2010m18, 0.767 for <jats:italic>MAL\u2010m1<\/jats:italic> and 0.762 for <jats:italic>miR\u2010124<\/jats:italic>\u20102. This indicates that <jats:italic>CADM1<\/jats:italic>\u2010m18 is not suitable as single marker. By varying the thresholds of both markers in the bi\u2010marker panels <jats:italic>CADM1<\/jats:italic>\u2010m18\/<jats:italic>MAL<\/jats:italic>\u2010m1, <jats:italic>CADM1<\/jats:italic>\u2010m18\/<jats:italic>miR\u2010124\u20102<\/jats:italic> and <jats:italic>MAL<\/jats:italic>\u2010m1\/<jats:italic>miR\u2010124<\/jats:italic>\u20102 upper and lower ROC curves were obtained, depicting the maximum and minimum CIN3+ sensitivity, respectively, at given specificity. For all these bi\u2010marker combinations, the upper curves were similar. However, for the <jats:italic>MAL<\/jats:italic>\u2010m1\/<jats:italic>miR\u2010124<\/jats:italic>\u20102 panel, the distance between upper and lower ROC curves was closest and this panel displayed the highest assay thresholds, indicating that this combination was most robust. At clinical specificities of 50 and 70%, the <jats:italic>MAL\u2010<\/jats:italic>m1\/<jats:italic>miR<\/jats:italic>\u2010<jats:italic>124\u20102<\/jats:italic> sensitivity for detection of CIN3+ ranged from 77.0 to 87.8% and from 64.9 to 71.6%, respectively. At 70% specificity thresholds no carcinomas were missed. By comparison, the CIN3+ sensitivity of HPV16\/18 genotyping on the self\u2010sampled lavage specimens was 58.1% (95%CI: 46.6\u201368.8) at a specificity of 87.7% (95%CI: 83.2\u201391.2). In conclusion, methylation analysis is a promising triage tool that in combination with HPV\u2010DNA testing offers feasible, full molecular screening on self\u2010collected cervico\u2010vaginal lavage specimens.<\/jats:p>","DOI":"10.1002\/ijc.28723","type":"journal-article","created":{"date-parts":[[2014,1,13]],"date-time":"2014-01-13T07:32:03Z","timestamp":1389598323000},"page":"880-886","source":"Crossref","is-referenced-by-count":60,"title":["Methylation marker analysis of self\u2010sampled cervico\u2010vaginal lavage specimens to triage high\u2010risk HPV\u2010positive women for colposcopy"],"prefix":"10.1002","volume":"135","author":[{"given":"A.T.","family":"Hesselink","sequence":"first","affiliation":[{"name":"Department of Pathology VU University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.A.M.","family":"Heideman","sequence":"additional","affiliation":[{"name":"Department of Pathology VU University Medical Center 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