{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:24:01Z","timestamp":1790429041459,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C569\/A10404\/CRUK"],"award-info":[{"award-number":["C569\/A10404\/CRUK"]}],"id":[{"id":"10.13039\/501100000289","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":[[2022,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The shift towards primary human papillomavirus (HPV)\u2010based screening has necessitated the search for a secondary triage test that provides sufficient sensitivity to detect high\u2010grade cervical intraepithelial neoplasia (CIN) and cancer, but also brings an improved specificity to avoid unnecessary clinical work and colposcopy referrals. We evaluated the performance of the previously described DNA\u2010methylation test (S5) in detecting CIN3 and cancers from diverse geographic settings in high\u2010, medium\u2010 and low\u2010income countries, using the cut\u2010off of 0.80 and exploratory cut\u2010offs of 2.62 and 3.70. Assays were performed using exfoliated cervical specimens (n\u00a0=\u00a0808) and formalin\u2010fixed biopsies (n\u00a0=\u00a0166) from women diagnosed with cytology\u2010negative results (n\u00a0=\u00a0220), CIN3 (n\u00a0=\u00a0204) and cancer stages I (n\u00a0=\u00a0245), II (n\u00a0=\u00a0249), III (n\u00a0=\u00a028) and IV (n\u00a0=\u00a022). Methylation increased proportionally with disease severity (Cuzick test for trend, <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.0001). S5 accurately separated women with negative\u2010histology from CIN3 or cancer (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.0001). At the 0.80 cut\u2010off, 543\/544 cancers were correctly identified as S5 positive (99.81%). At cut\u2010off 3.70, S5 showed a sensitivity of 95.77% with improved specificity. The S5 odds ratios of women negative for cervical disease vs CIN3+ were significantly higher than for HPV16\/18 genotyping at all cut\u2010offs (all <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.0001). At S5 cut\u2010off 0.80, 96.15% of consistently high\u2010risk human papillomavirus (hrHPV)\u2010negative cancers (tested with multiple hrHPV\u2010genotyping assay) were positive by S5. These cancers may have been missed in current primary hrHPV\u2010screening programmes. The S5 test can accurately detect CIN3 and malignancy irrespective of geographic context and setting. The test can be used as a screening and triage tool. Adjustment of the S5 cut\u2010off can be performed considering the relative importance given to sensitivity vs specificity.<\/jats:p>","DOI":"10.1002\/ijc.33815","type":"journal-article","created":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T13:20:13Z","timestamp":1632576013000},"page":"290-302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Clinical performance of methylation as a biomarker for cervical carcinoma in\u2009situ and cancer diagnosis: A worldwide study"],"prefix":"10.1002","volume":"150","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3078-104X","authenticated-orcid":false,"given":"Cristiana","family":"Banila","sequence":"first","affiliation":[{"name":"Centre for Cancer Prevention Wolfson Institute of Population Health, Queen Mary University of London  London 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birhanu","family":"Kumbi","sequence":"additional","affiliation":[{"name":"Department of Microbial, Cellular and Molecular Biology, College of Natural and Computational Sciences Addis Ababa University  Addis Ababa Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dereje","family":"Beyene","sequence":"additional","affiliation":[{"name":"Department of Microbial, Cellular and Molecular Biology, College of Natural and Computational Sciences Addis Ababa University  Addis Ababa Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosette M.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Centre for HPV Prevention University of New Mexico Comprehensive Cancer Centre  Albuquerque New Mexico 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