{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:23:54Z","timestamp":1791339834886,"version":"4.3.1"},"reference-count":95,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Early identification of the risk of malignant transformation in oral potentially malignant disorders (OPMDs) is critical for improving outcomes in oral squamous cell carcinoma (OSCC). This comprehensive review examines immunological biomarkers obtained from minimally invasive oral cytobrush (OCB) specimens for the early detection of OSCC within a precision medicine framework. The objectives were to (1) identify and characterise key immunological biomarkers associated with early oral carcinogenesis; (2) evaluate the diagnostic utility of OCB sampling for detecting these biomarkers; and (3) explore the potential of OCB-based profiling to support personalised screening and patient management. The review highlights the potential advantages of OCB compared with conventional diagnostic methods, as reported in the literature, particularly its ability to capture early malignant changes through immunological analysis. Evidence is discussed for biomarker pathways related to cell-cycle and differentiation dysregulation (p53, Ki-67, CKs), inflammation-driven epithelial transformation (IL-1\u03b2, IL-6, IL-8, TNF-\u03b1), and immune suppression and checkpoint activation (PD-L1, B7-H6). OCB provides reliable and patient-friendly cyto-salivary samples that are suitable for immunological and molecular analyses. Aberrant biomarker expression detected in OCB specimens correlates with epithelial dysplasia and reflects early non-invasive neoplastic transformation, supporting the diagnostic value of integrated biomarker panels. Overall, OCB-based immunoanalysis represents a practical, non-invasive approach for the early detection of OSCC. Emerging technologies, including AI and multi-omics approaches, may further support the precision and predictive values of immunological analysis for OSCC. When combined with relevant biomarker pathways reflecting tumour biology and host immune responses, this strategy could offer a strong foundation for precision-medicine screening. It may also support personalised monitoring in patients with OPMDs.<\/jats:p>","DOI":"10.3390\/ijms27042059","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T08:58:21Z","timestamp":1771837101000},"page":"2059","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunological Analysis of Oral Cytobrush Specimens for Early Detection of Oral Cancer Biomarkers: A Comprehensive Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2882-2156","authenticated-orcid":false,"given":"Reem","family":"Hanna","sequence":"first","affiliation":[{"name":"Department of Restorative Dental Sciences, Eastman Dental Institute, Medical Faculty, University College London, London WC1E 6DE, UK"},{"name":"Head and Neck Academic Centre, Integrated Research, Division of Surgery and Interventional Science, Medical Faculty, University College London, London W1W 7TY, UK"},{"name":"Dental Faculty, Royal College of Surgeons Ireland, 21\u2013122 St Stephen\u2019s Green, Dublin 2, D02 H903 Dublin, Ireland"},{"name":"Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Viale Benedetto XV, 6, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2977-6318","authenticated-orcid":false,"given":"Alberto Luigi","family":"Rebaudi","sequence":"additional","affiliation":[{"name":"Private Dental Practice, Piazza della Vittoria 8\/12, 16121 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2103-0746","authenticated-orcid":false,"given":"Saman","family":"Warnakulasuriya","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, Oral & Craniofacial Sciences, King\u2019s College London, London SE1 9SP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9365-0641","authenticated-orcid":false,"given":"Senada","family":"Koljenovic","sequence":"additional","affiliation":[{"name":"Department of Pathology, Antwerp University Hospital, 2650 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6503-1201","authenticated-orcid":false,"given":"Maria","family":"Menini","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Viale Benedetto XV, 6, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Lagan\u00e0","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Surgery, Unit\u00e0 Operativa Complessa di Chirugia Maxillofaciale Odontoiatra, IRCCS Ospedale San Martino, Largo Rosanna Benzi, 10, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2184-3931","authenticated-orcid":false,"given":"Bernardo","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Surgery, Unit\u00e0 Operativa Complessa di Chirugia Maxillofaciale Odontoiatra, IRCCS Ospedale San Martino, Largo Rosanna Benzi, 10, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Iacoviello","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Surgery, Galliera Hospital, Via Mura delle Cappuccine 14, 16128 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2631-1551","authenticated-orcid":false,"given":"Mauro","family":"Labanca","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiopathology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Greppi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES), University of Genoa, Via Leon Battista Alberti 2, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0549-5829","authenticated-orcid":false,"given":"Federico","family":"Rebaudi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES), University of Genoa, Via Leon Battista Alberti 2, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9798-4944","authenticated-orcid":false,"given":"Silvia","family":"Pesce","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES), University of Genoa, Via Leon Battista Alberti 2, 16132 Genoa, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7277-668X","authenticated-orcid":false,"given":"Alberto","family":"Rebaudi","sequence":"additional","affiliation":[{"name":"Private Dental Practice, Piazza della Vittoria 8\/12, 16121 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4103-7566","authenticated-orcid":false,"given":"Emanuela","family":"Marcenaro","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES), University of Genoa, Via Leon Battista Alberti 2, 16132 Genoa, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3721","DOI":"10.3390\/curroncol30040283","article-title":"Oral 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