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However, the best methodology is still undetermined. Host DNA methylation markers <jats:italic>CADM1, MAL<\/jats:italic> and <jats:italic>miR124<\/jats:italic> have been identified in cervical disease, but not anal disease. Anal swabs varying by disease grade were assessed for DNA methylation of <jats:italic>CADM1, MAL<\/jats:italic> and <jats:italic>miR124-2.<\/jats:italic> Each marker was compared across disease grades, stratified by HPV and HIV status. Receiver operating characteristic curves identified the predictive value of significant gene candidates. <jats:italic>CADM1<\/jats:italic> methylation was significantly higher in high-grade squamous intraepithelial lesions (HSIL) compared with low-grade (LSIL) (p\u2009=\u20090.005) or normal (p\u2009&lt;\u20090.001) samples with 67.2% correctly identified as HSIL. <jats:italic>MAL<\/jats:italic> methylation was significantly (p\u2009=\u20090.002) increased in HSIL compared with LSIL in HIV positive participants with 79.8% correctly indicated as HSIL. Gene <jats:italic>miR124-2,<\/jats:italic> showed no difference between disease grades. Biomarkers with established diagnostic value in cervical disease have limited utility in the prediction of anal disease, with <jats:italic>CADM1<\/jats:italic> identified as a marker with screening potential in a gay and bisexual men (GBM) population and <jats:italic>MAL<\/jats:italic> in HIV positive GBM population. New markers specific to the anal mucosa are required to improve triage of high-risk individuals.<\/jats:p>","DOI":"10.1038\/s41598-022-07258-5","type":"journal-article","created":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T11:02:42Z","timestamp":1646305362000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia"],"prefix":"10.1038","volume":"12","author":[{"given":"Samuel","family":"Phillips","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kahli","family":"Cassells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M.","family":"Garland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy A.","family":"Machalek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Templeton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyi","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. 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Roberts reports other from Hologic Australia (Thin Prep consumables) during the conduct of the study and other from Roche Australia (donated antibodies for further research in this field) outside the submitted work. I.M. Poynten reports other from Seqirus (travel funding) outside the submitted work. M. Molano reports grants from Cancer Council Victoria (project: evaluating molecular biomarkers of anal cancer risk, application no. APP1130507) during the conduct of the study. D.A. Machalek reports nonfinancial support from MSD and Seqirus, grants from Seqirus, and other from Roche Diagnostics (manuscript license sponsorship) outside the submitted work. F. Jin reports grants from the National Health and Medical Research Council and Cancer Council New South Wales during the conduct of the study. S.M. Garland reports grants (to institution for researcher-initiated grant for HPV young women's study), personal fees (lecture fees; work performed in personal time), and other from Merck (global advisory board member for HPV) outside the submitted work. A.E. Grulich reports grants from the National Health and Medical Research Council during the conduct of the study. A.M. Cornall reports grants from Cancer Council Victoria during the conduct of the study. No potential conflicts of interest were disclosed by the other authors.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3565"}}