{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:27:54Z","timestamp":1791959274515,"version":"4.3.4"},"reference-count":27,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,2,13]],"date-time":"2012-02-13T00:00:00Z","timestamp":1329091200000},"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":[[2012,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cervical neoplasia\u2010specific biomarkers, <jats:italic>e.g.<\/jats:italic> DNA methylation markers, with high sensitivity and specificity are urgently needed to improve current population\u2010based screening on (pre)malignant cervical neoplasia. We aimed to identify new cervical neoplasia\u2010specific DNA methylation markers and to design and validate a methylation marker panel for triage of high\u2010risk human papillomavirus (hr\u2010HPV) positive patients. First, high\u2010throughput quantitative methylation\u2010specific PCRs (QMSP) on a novel OpenArray\u2122 platform, representing 424 primers of 213 cancer specific methylated genes, were performed on frozen tissue samples from 84 cervical cancer patients and 106 normal cervices. Second, the top 20 discriminating methylation markers were validated by LightCycler\u00ae MSP on frozen tissue from 27 cervical cancer patients and 20 normal cervices and ROCs and test characteristics were assessed. Three new methylation markers were identified (<jats:italic>JAM3<\/jats:italic>, <jats:italic>EPB41L3<\/jats:italic> and <jats:italic>TERT<\/jats:italic>), which were subsequently combined with <jats:italic>C13ORF18<\/jats:italic> in our four\u2010gene methylation panel. In a third step, our methylation panel detected in cervical scrapings 94% (70\/74) of cervical cancers, while in a fourth step 82% (32\/39) cervical intraepithelial neoplasia grade 3 or higher (CIN3+) and 65% (44\/68) CIN2+ were detected, with 21% positive cases for \u2264CIN1 (16\/75). Finally, hypothetical scenario analysis showed that primary hr\u2010HPV testing combined with our four\u2010gene methylation panel as a triage test resulted in a higher identification of CIN3 and cervical cancers and a higher percentage of correct referrals compared to hr\u2010HPV testing in combination with conventional cytology. In conclusion, our four\u2010gene methylation panel might provide an alternative triage test after primary hr\u2010HPV testing.<\/jats:p>","DOI":"10.1002\/ijc.26326","type":"journal-article","created":{"date-parts":[[2011,7,27]],"date-time":"2011-07-27T18:52:12Z","timestamp":1311792732000},"page":"1861-1869","source":"Crossref","is-referenced-by-count":109,"title":["A four\u2010gene methylation marker panel as triage test in high\u2010risk human papillomavirus positive 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