{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:54:04Z","timestamp":1790931244617,"version":"4.1.0"},"reference-count":63,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To synthesise biological biomarker evidence in proliferative verrucous leukoplakia\/proliferative leukoplakia and quantify malignant transformation using eligible longitudinal evidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Primary human biomarker studies and longitudinal studies reporting extractable malignant\u2010transformation events and denominators were systematically reviewed. Biomarker evidence was synthesised narratively. Malignant\u2010transformation proportions were pooled using a random\u2010effects model, with conservative handling of potentially overlapping cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Forty\u2010one publications contributed to the biomarker synthesis, spanning genetic, genomic, DNA\u2010ploidy, epigenetic, transcriptomic, proteomic, immunohistochemical, immunologic, viral, microbiome, salivary, and circulating markers. No biomarker had sufficient independent validation for clinical diagnostic or prognostic use. Twenty independent or conservatively non\u2010overlapping study estimates comprising 745 patients and 243 malignant\u2010transformation events contributed to the meta\u2010analysis. The pooled malignant\u2010transformation proportion was 34.13% (95% confidence interval 26.62\u201342.53), with substantial heterogeneity and a 95% prediction interval of 13.85%\u201362.56%. Results remained stable in sensitivity and leave\u2010one\u2010out analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Diverse biological alterations have been reported, but none currently supports routine biomarker\u2010based diagnosis or individual risk stratification. Malignant transformation is frequent, although substantial between\u2010study variability limits interpretation of the pooled estimate as an individual patient risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.70520","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:14:21Z","timestamp":1790928861000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biological Biomarkers in Proliferative Verrucous Leukoplakia: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0315-1560","authenticated-orcid":false,"given":"Madawi Faisal","family":"Alkeheli","sequence":"first","affiliation":[{"name":"Oral Diagnostic Sciences Department, Faculty of Dentistry King Abdulaziz University  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5901-8975","authenticated-orcid":false,"given":"Hisham I.","family":"Othman","sequence":"additional","affiliation":[{"name":"Oral Diagnostic Sciences Department, Faculty of Dentistry King Abdulaziz University  Jeddah Saudi Arabia"},{"name":"Department of Oral Biology, Faculty of Dentistry Alexandria University  Alexandria Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2023.152104"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oooo.2014.10.023"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12503"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379\u2010022\u201001021\u2010x"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijom.2022.01.002"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.labinv.2023.100222"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.18\u20100620"},{"issue":"2","key":"e_1_2_12_9_1","first-page":"E110","article-title":"Epstein\u2010Barr Virus in Oral Proliferative Verrucous Leukoplakia and Squamous Cell Carcinoma: A Preliminary Study","volume":"13","author":"Bagan J. 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