{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:57:40Z","timestamp":1782824260132,"version":"3.54.5"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,11,18]],"date-time":"2018-11-18T00:00:00Z","timestamp":1542499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["PI17\/00772"],"award-info":[{"award-number":["PI17\/00772"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15\/00546"],"award-info":[{"award-number":["PI15\/00546"]}],"id":[{"id":"10.13039\/501100004587","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":[[2019,1]]},"abstract":"<jats:p>Cervical screening aims to identify women with high\u2010grade squamous intraepithelial lesion\/cervical intraepithelial neoplasia 2\u20103 (HSIL\/CIN2\u20103) or invasive cervical cancer (ICC). Identification of women with severe premalignant lesions or ICC (CIN3+) could ensure their rapid treatment and prevent overtreatment. We investigated high\u2010risk human papillomavirus (hrHPV) detection with genotyping and methylation of FAM19A4\/miR124\u20102 for detection of CIN3+ in 538 women attending colposcopy for abnormal cytology. All women had an additional cytology with hrHPV testing (GP5+\/6+\u2010PCR\u2010EIA+), genotyping (HPV16\/18, HPV16\/18\/31\/45), and methylation analysis (FAM19A4\/miR124\u20102) and at least one biopsy. CIN3+ detection was studied overall and in women &lt;30 (<jats:italic>n<\/jats:italic> = 171) and \u226530 years (<jats:italic>n<\/jats:italic> = 367). Positivity for both rather than just one methylation markers increased in CIN3, and all ICC was positive for both. Overall sensitivity and specificity for CIN3+ were, respectively, 90.3% (95%CI 81.3\u201395.2) and 31.8% (95%CI 27.7\u201336.1) for hrHPV, 77.8% (95%CI 66.9\u201385.8) and 69.3% (95%CI 65.0\u201373.3) for methylation biomarkers and 93.1% (95%CI 84.8\u201397.0) and 49.4% (95%CI 44.8\u201353.9) for combined HPV16\/18 and\/or methylation positivity. For CIN3, hrHPV was found in 90.9% (95%CI 81.6\u201395.8), methylation positivity in 75.8% (95%CI 64.2\u201384.5) and HPV16\/18 and\/or methylation positivity in 92.4% (95%CI 83.5\u201396.7). In women aged \u226530, the sensitivity of combined HPV16\/18 and methylation was increased (98.2%, 95%CI 90.6\u201399.7) with a specificity of 46.3% (95%CI 40.8\u201351.9). Combination of HPV16\/18 and methylation analysis was very sensitive and offered improved specificity for CIN3+, opening the possibility of rapid treatment for these women and follow\u2010up for women with potentially regressive, less advanced, HSIL\/CIN2 lesions.<\/jats:p>","DOI":"10.1002\/ijc.31787","type":"journal-article","created":{"date-parts":[[2018,8,11]],"date-time":"2018-08-11T07:09:55Z","timestamp":1533971395000},"page":"160-168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Reliable identification of women with CIN3+ using hrHPV genotyping and methylation markers in a cytology\u2010screened referral population"],"prefix":"10.1002","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5882-7778","authenticated-orcid":false,"given":"Annemiek","family":"Leeman","sequence":"first","affiliation":[{"name":"DDL Diagnostic Laboratory  Rijswijk The 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