{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:08:42Z","timestamp":1790968122601,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["2016\u201010781"],"award-info":[{"award-number":["2016\u201010781"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:p>\n                    Anal cancer has increasing incidence and is preceded by high\u2010grade anal intraepithelial neoplasia (HGAIN; AIN2\u20133). Previously, we identified and validated several methylation markers for accurate detection of anal cancer and HGAIN with cancer risk in HIV\u2010positive (HIV+) men who have sex with men (MSM). This study aimed to evaluate these markers in HIV\u2010negative risk groups. A cross\u2010sectional series of 176 tissue samples of anal cancer, AIN3, AIN2, AIN1 and control biopsies obtained in HIV\u2010negative women and men was tested for six methylation markers (\n                    <jats:italic>ASCL1, LHX8, SST, WDR17, ZIC1<\/jats:italic>\n                    and\n                    <jats:italic>ZNF582<\/jats:italic>\n                    ). Accuracy for detection of AIN3 and cancer (AIN3+) was determined by univariable and multivariable mixed\u2010effect ordinal logistic regression. Methylation levels of all markers increased with increasing severity of disease (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a00.0001) and were comparable to results in HIV+ MSM. All markers showed high accuracy for AIN3+ detection [area under the curve (AUC): 0.83\u20130.86]. The optimal marker panel (\n                    <jats:italic>ASCL1<\/jats:italic>\n                    and\n                    <jats:italic>ZIC1<\/jats:italic>\n                    ; AUC\u00a0=\u00a00.85 for AIN3+) detected 98% of cancers at 79% specificity. In conclusion, DNA methylation markers show a high diagnostic performance for AIN3+ detection in HIV+ and HIV\u2010negative risk groups, justifying broad application of methylation analysis for anal cancer prevention programmes.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.12926","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T23:35:26Z","timestamp":1613172926000},"page":"3024-3036","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["DNA methylation markers have universal prognostic value for anal cancer risk in HIV\u2010negative and HIV\u2010positive individuals"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1325-1901","authenticated-orcid":false,"given":"Ramon P.","family":"van der Zee","sequence":"first","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands"},{"name":"Department of Internal Medicine Division of Infectious Diseases Amsterdam Institute for Infection and Immunity Amsterdam UMC University of Amsterdam Amsterdam The Netherlands"},{"name":"Department of Dermatology Amsterdam UMC University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carel J.M.","family":"van Noesel","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivonne","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Data Science Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo J.","family":"ter Braak","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00eblle A.M.","family":"Heideman","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry J.C.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Dermatology Amsterdam UMC University of Amsterdam Amsterdam The Netherlands"},{"name":"STI Outpatient Clinic Department of Infectious Diseases Public Health Service of Amsterdam (GGD Amsterdam) Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M.","family":"Prins","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Infectious Diseases Amsterdam Institute for Infection and Immunity Amsterdam UMC University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2327-9839","authenticated-orcid":false,"given":"Renske D.M.","family":"Steenbergen","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,16]]},"reference":[{"key":"e_1_2_11_2_1","first-page":"924","article-title":"International trends in anal cancer incidence rates","volume":"46","author":"Islami F","year":"2017","journal-title":"Int J Epidemiol"},{"key":"e_1_2_11_3_1","first-page":"401","article-title":"The increasing incidence of anal cancer: can it be explained by trends in risk groups?","volume":"71","author":"Zee RP","year":"2013","journal-title":"Neth J 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