{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T05:53:40Z","timestamp":1781589220625,"version":"3.54.5"},"reference-count":23,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Premalignant laryngeal lesions carry a variable risk of malignant transformation to squamous cell carcinoma. Identifying reliable biomarkers that predict malignant transformation could improve patient management and surveillance strategies. The objective of this work is to perform a systematic review of the literature on biomarkers that predict malignant transformation of premalignant laryngeal lesions. Methods: We conducted a systematic review following PRISMA 2020 guidelines. The PubMed, Scopus and Embase databases, and Google Scholar were searched for studies published between January 2011 and November 2025. Studies investigating biomarkers that predict malignant transformation of histopathologically confirmed premalignant laryngeal lesions were included. Risk of bias was assessed using the ROBINS-I tool. Results: From 166 initially identified records, 11 studies met the inclusion criteria, including 730 patients. These studies investigated diverse biomarker categories such as protein markers (cortactin, FAK, NANOG, SOX2, CSPG4), immune markers (tumor-infiltrating lymphocytes, immune gene signatures), microRNAs (miR-183-5p, miR-155-5p, miR-106b-3p), and genetic markers (chromosomal instability, PIK3CA amplification and mutations, FGFR3 mutations). Five studies provided adequate follow-up data on transformation outcomes. Most studies showed a moderate to serious risk of bias primarily due to limited confounder control and incomplete reporting. Conclusions: While several promising biomarker candidates have been identified, the evidence base remains limited due to small sample sizes, heterogeneous methodologies, and inadequate follow-up data. Cortactin\/FAK protein expression and immune signatures are the most promising but require validation in larger, well-designed prospective cohorts.<\/jats:p>","DOI":"10.3390\/diagnostics16020236","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T07:30:34Z","timestamp":1768203034000},"page":"236","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Biomarkers for Predicting Malignant Transformation of Premalignant Lesions of the Larynx: A Systematic Review"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3063-0890","authenticated-orcid":false,"given":"Juan P.","family":"Rodrigo","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Hospital Universitario Central de Asturias, University of Oviedo, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias, Instituto Universitario de Oncolog\u00eda del Principado de Asturias, 33011 Oviedo, Spain"},{"name":"CIBER de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5045-6960","authenticated-orcid":false,"given":"Reydson Alcides","family":"de Lima-Souza","sequence":"additional","affiliation":[{"name":"Department of Oral Diagnosis, Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas (UNICAMP), Piracicaba 13414-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Hospital Universitario Central de Asturias, University of Oviedo, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias, Instituto Universitario de Oncolog\u00eda del Principado de Asturias, 33011 Oviedo, Spain"},{"name":"CIBER de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1017-7363","authenticated-orcid":false,"given":"G\u00f6ran","family":"Stenman","sequence":"additional","affiliation":[{"name":"Department of Pathology, Sahlgrenska Center for Cancer Research, Sahlgrenska University Hospital, University of Gothenburg, 405 30 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbas","family":"Agaymy","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2563-6729","authenticated-orcid":false,"given":"Miquel","family":"Quer","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Hospital Santa Creu y Sant Pau, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7933-4585","authenticated-orcid":false,"given":"Vinidh","family":"Paleri","sequence":"additional","affiliation":[{"name":"The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilmo","family":"Leivo","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, Pathology, University of Turku, Turku University Hospital, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5366-093X","authenticated-orcid":false,"given":"Alfons","family":"Nadal","sequence":"additional","affiliation":[{"name":"Pathology Department, Cl\u00ednic Barcelona, Basic Clinical Practice Department, Universitat de Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer, 08007 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6866-3220","authenticated-orcid":false,"given":"Nina","family":"Zidar","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda V.","family":"Mariano","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9998-8212","authenticated-orcid":false,"given":"Henrik","family":"Hellquist","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Medicine, Algarve Biomedical Center Research Institute, University of Algarve, 8005-139 Faro, Portugal"},{"name":"Department of Cellular Pathology, Northern Lincolnshire and Goole NHS Foundation Trust, Lincoln LN2 5QY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Gale","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8247-8002","authenticated-orcid":false,"given":"Alfio","family":"Ferlito","sequence":"additional","affiliation":[{"name":"International Head and Neck Scientific Group, 35100 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and neck squamous cell carcinoma","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat. 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