{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T21:49:49Z","timestamp":1793742589839,"version":"4.6.1"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T00:00:00Z","timestamp":1603238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2021,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In human papillomavirus (HPV) cervical cancer screening, cytology is used as triage to counter the low specificity of HPV testing. VALID\u2010SCREEN is a EU\u2010multicenter, retrospective study conducted to evaluate the clinical performance of the FAM19A4\/miR124\u20102 methylation\u2010based molecular triage test as a substitute or addition to cytology as reflex testing of HPV screen positive women. FAM19A4\/miR124\u20102 methylation test (QIAsure Methylation Test) was evaluated in 2384 HPV\u2010positive cervical screening samples, from women 29\u201076\u2009years of age, derived from four EU countries. Specimens were collected in ThinPrep or SurePath media, HPV\u2010status, concurrent cytology, and histology diagnosis were provided by the parent institutes. The control population consisted of women with no evidence of disease within 2\u2009years of follow\u2010up. A total of 899 histologies were retrieved; 527 showed no disease, 124 CIN2 (5.2%), 228 CIN3 (9.6%) and 20 cervical cancers (0.8%); 19 of 20 screen\u2010detected cervical cancers were found methylation\u2010positive (sensitivity 95%). Overall specificity of FAM19A4\/miR124\u20102 methylation test was 78.3% (n = 2013; 95%CI: 76\u201080). The negative predictive value of hrHPV positive, methylation\u2010negative outcomes were 99.9% for cervical cancer (N = 1694; 95%CI: 99.6\u201099.99), 96.9% for \u2265CIN3 (95%CI: 96\u201098), and 93.0% for \u2265CIN2 (95%CI: 92\u201094). Overall sensitivity for CIN3 using FAM19A4\/miR124\u20102 methylation test was 77% (n = 228; 95%CI: 71\u201082). CIN3 sensitivity was uniform between centers independent of sample collection medias, DNA extraction methods and HPV screening tests. Being objectively reported compared to the subjectivity of cytology, equally performing across settings and screening methods, the\n                    <jats:italic>FAM19A4\/miR124\u20102<\/jats:italic>\n                    methylation constitute an alternative\/supplement to cytology as triage method to be investigated in real\u2010life pilot implementation.\n                  <\/jats:p>","DOI":"10.1002\/ijc.33320","type":"journal-article","created":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T16:04:23Z","timestamp":1601481863000},"page":"396-405","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":132,"title":["Methylation markers\n                    <scp>\n                      <i>FAM19A4<\/i>\n                    <\/scp>\n                    and\n                    <i>\n                      <scp>miR124<\/scp>\n                      \u20102\n                    <\/i>\n                    as triage strategy for primary human papillomavirus screen positive women: A large European multicenter study"],"prefix":"10.1002","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4853-6747","authenticated-orcid":false,"given":"Jesper","family":"Bonde","sequence":"first","affiliation":[{"name":"Molecular Pathology Laboratory, Department of Pathology Hvidovre Hospital  Hvidovre Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arno","family":"Floore","sequence":"additional","affiliation":[{"name":"Self\u2010screen B.V  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ditte","family":"Ejegod","sequence":"additional","affiliation":[{"name":"Molecular Pathology Laboratory, Department of Pathology Hvidovre Hospital  Hvidovre Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4951-9167","authenticated-orcid":false,"given":"Frederique J.","family":"Vink","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albertus","family":"Hesselink","sequence":"additional","affiliation":[{"name":"Self\u2010screen B.V  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"van de Ven","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja O\u0161trbenk","family":"Valen\u010dak","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Immunology University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helle","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Molecular Pathology Laboratory, Department of Pathology Hvidovre Hospital  Hvidovre Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Doorn","sequence":"additional","affiliation":[{"name":"Self\u2010screen B.V  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim G.","family":"Quint","sequence":"additional","affiliation":[{"name":"DDL Diagnostic Laboratory  Rijswijk The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5875-9840","authenticated-orcid":false,"given":"Karl Ulrich","family":"Petry","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics  Klinikum Wolfsburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Poljak","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Immunology University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazyna","family":"Stanczuk","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Western Isles Hospital  Scotland UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2604-3928","authenticated-orcid":false,"given":"Kate","family":"Cuschieri","sequence":"additional","affiliation":[{"name":"HPV Research Group, Division of Pathology University of Edinburgh  Scotland UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"de Sanjos\u00e9","sequence":"additional","affiliation":[{"name":"Infections and Cancer Laboratory Catalan Institute of Oncology (ICO)  Barcelona 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