{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T12:39:05Z","timestamp":1793191145021,"version":"4.5.0"},"reference-count":243,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Hubei Province of China","award":["2025AFB481"],"award-info":[{"award-number":["2025AFB481"]}]},{"name":"Natural Science Foundation of Hubei Province of China","award":["2024AFB1005"],"award-info":[{"award-number":["2024AFB1005"]}]},{"name":"Natural Science Foundation of Hubei Province of China","award":["2024AFB278"],"award-info":[{"award-number":["2024AFB278"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oral squamous cell carcinoma (OSCC) frequently develops within chronically injured oral mucosa and may be preceded by clinically recognizable oral potentially malignant disorders (OPMDs), which provide an important window for cancer interception. This review examines how etiological exposures, persistent inflammation, and lesion-specific epithelial\u2013stromal\u2013immune interactions cooperate during the transition from mucosal injury to dysplasia, carcinoma in situ, and invasive OSCC. Major carcinogenic exposures, including tobacco, alcohol, and areca nut, are considered together with context-dependent contributors such as microbial dysbiosis, viral infection, and immune-mediated epithelial injury. At the molecular level, inflammation-driven oral carcinogenesis involves cytokine and chemokine amplification, oxidative and nitrosative stress, NF-\u03baB and STAT3 activation, the COX-2\/PGE2 axis, genomic instability, field cancerization, epithelial\u2013stromal crosstalk, angiogenesis, immune dysregulation, and epigenetic and non-coding RNA-mediated reprogramming. Emerging tools such as molecular risk assessment, liquid biopsy, optical imaging, spatially resolved profiling, and artificial intelligence-assisted models may improve identification of high-risk lesions, although most biomarkers require further prospective validation. Prevention should therefore integrate exposure control, biopsy-based diagnosis, local treatment when indicated, long-term surveillance, and trial-based precision strategies according to lesion risk, intervention window, and safety profile. This review supports a shift from lesion-centered management toward risk-adapted precision prevention in inflammation-driven oral carcinogenesis.<\/jats:p>","DOI":"10.3390\/ijms27125632","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"5632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["From Chronic Inflammation to Malignancy: Molecular Mechanisms and Therapeutic Insights in Oral Carcinogenesis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8651-4958","authenticated-orcid":false,"given":"Ying-Jia","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaiping","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyuan","family":"Lv","sequence":"additional","affiliation":[{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronghua","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingfeng","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9003-9729","authenticated-orcid":false,"given":"Zixuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangyuan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"878","DOI":"10.4065\/82.7.878","article-title":"Oral Cancer","volume":"82","author":"Kademani","year":"2007","journal-title":"Mayo Clin. Proc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.oraloncology.2008.06.002","article-title":"Global epidemiology of oral and oropharyngeal cancer","volume":"45","author":"Warnakulasuriya","year":"2009","journal-title":"Oral Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1600-0714.2009.00845.x","article-title":"Oral cancer over four decades: Epidemiology, trends, histology, and survival by anatomical sites","volume":"39","author":"Zini","year":"2010","journal-title":"J. Oral Pathol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1111\/odi.13704","article-title":"Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer","volume":"27","author":"Warnakulasuriya","year":"2020","journal-title":"Oral Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1111\/jop.13440","article-title":"Malignant transformation rate of oral leukoplakia in the past 20\u2009years: A systematic review and meta-analysis","volume":"52","author":"Guan","year":"2023","journal-title":"J. Oral Pathol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1111\/odi.13810","article-title":"Malignant transformation of oral leukoplakia: Systematic review and meta-analysis of the last 5 years","volume":"27","author":"Warnakulasuriya","year":"2021","journal-title":"Oral Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1111\/jop.13304","article-title":"Critical update, systematic review, and meta-analysis of oral erythroplakia as an oral potentially malignant disorder","volume":"51","year":"2022","journal-title":"J. Oral Pathol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1111\/odi.13831","article-title":"Malignant transformation of oral proliferative verrucous leukoplakia: A systematic review and meta-analysis","volume":"27","author":"Mello","year":"2021","journal-title":"Oral Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Murthy, V., Mylonas, P., Carey, B., Yogarajah, S., Farnell, D., Addison, O., Cook, R., Escudier, M., Diniz-Freitas, M., and Limeres, J. (2022). Malignant Transformation Rate of Oral Submucous Fibrosis: A Systematic Review and Meta-Analysis. J. Clin. Med., 11.","DOI":"10.3390\/jcm11071793"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Moles, M.\u00c1., and Ramos-Garc\u00eda, P. (2024). An Evidence-Based Update on the Potential for Malignancy of Oral Lichen Planus and Related Conditions: A Systematic Review and Meta-Analysis. Cancers, 16.","DOI":"10.3390\/cancers16030608"},{"key":"ref_12","unstructured":"IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2012). Personal Habits and Indoor Combustions\u2014IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, IARC Publications."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e13198","DOI":"10.1016\/j.heliyon.2023.e13198","article-title":"Microbial dysbiosis in oral squamous cell carcinoma: A systematic review and meta-analysis","volume":"9","author":"Yu","year":"2023","journal-title":"Heliyon"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sukmana, B.I., Saleh, R.O., Najim, M.A., Al-Ghamdi, H.S., Achmad, H., Al-Hamdani, M.M., Taher, A.A.Y., Alsalamy, A., Khaledi, M., and Javadi, K. (2024). Oral microbiota and oral squamous cell carcinoma: A review of their relation and carcinogenic mechanisms. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1319777"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tang, K.D., Menezes, L., Baeten, K., Walsh, L.J., Whitfield, B.C.S., Batstone, M.D., Kenny, L., Frazer, I.H., Scheper, G.C., and Punyadeera, C. (2020). Oral HPV16 Prevalence in Oral Potentially Malignant Disorders and Oral Cavity Cancers. Biomolecules, 10.","DOI":"10.3390\/biom10020223"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1056\/NEJMoa0912217","article-title":"Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer","volume":"363","author":"Ang","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_17","first-page":"201","article-title":"A Systematic Review of Interleukin-17 in Oral Lichen Planus: From Etiopathogenesis to Treatment","volume":"21","author":"Moosavi","year":"2024","journal-title":"Clin. Med. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kumari, P., Debta, P., and Dixit, A. (2022). Oral Potentially Malignant Disorders: Etiology, Pathogenesis, and Transformation into Oral Cancer. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.825266"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/nrc2191","article-title":"Molecular mechanisms of alcohol-mediated carcinogenesis","volume":"7","author":"Seitz","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Stornetta, A., Guidolin, V., and Balbo, S. (2018). Alcohol-Derived Acetaldehyde Exposure in the Oral Cavity. Cancers, 10, Correction in Cancers 2018, 10, 74. https:\/\/doi.org\/10.3390\/cancers10030074.","DOI":"10.3390\/cancers10030074"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.oraloncology.2005.08.005","article-title":"Oral submucous fibrosis: Review on aetiology and pathogenesis","volume":"42","author":"Tilakaratne","year":"2006","journal-title":"Oral Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Immunity, Inflammation, and Cancer","volume":"140","author":"Grivennikov","year":"2010","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nri3012","article-title":"Inflammasome shapes the microbiota","volume":"11","author":"Papatriantafyllou","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrclinonc.2018.8","article-title":"Targeting the IL-6\/JAK\/STAT3 signalling axis in cancer","volume":"15","author":"Johnson","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nrc3818","article-title":"Revisiting STAT3 signalling in cancer: New and unexpected biological functions","volume":"14","author":"Yu","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1196\/annals.1352.026","article-title":"Transcription Factor NF-\u03baB: A Sensor for Smoke and Stress Signals","volume":"1056","author":"Ahn","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Brierly, G., Celentano, A., Breik, O., Moslemivayeghan, E., Patini, R., McCullough, M., and Yap, T. (2023). Tumour Necrosis Factor Alpha (TNF-\u03b1) and Oral Squamous Cell Carcinoma. Cancers, 15.","DOI":"10.3390\/cancers15061841"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s13046-018-0887-z","article-title":"Relationship between epithelial-to-mesenchymal transition and the inflammatory microenvironment of hepatocellular carcinoma","volume":"37","author":"Yan","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11125","DOI":"10.1158\/0008-5472.CAN-06-3174","article-title":"Tumor Necrosis Factor-\u03b1 Increases Reactive Oxygen Species by Inducing Spermine Oxidase in Human Lung Epithelial Cells: A Potential Mechanism for Inflammation-Induced Carcinogenesis","volume":"66","author":"Babbar","year":"2006","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"35","DOI":"10.4103\/jioh.jioh_71_24","article-title":"Prospective Evaluation of KEAP1, NRF-2, NF-\u03baB, IL-1\u03b2, and TNF\u03b1 Levels in Head and Neck Cancer Patients with Oral Mucositis Undergoing Chemo-radiotherapy","volume":"18","author":"Dharman","year":"2026","journal-title":"J. Int. Oral Health"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ijom.2019.06.001","article-title":"Influence of tumour necrosis factor alpha on epithelial\u2013mesenchymal transition of oral cancer cells in co-culture with mesenchymal stromal cells","volume":"49","author":"Holzenburg","year":"2020","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chellappan, S.P., Wang, H., Wang, H.-S., Zhou, B.-H., Li, C.-L., Zhang, F., Wang, X.-F., Zhang, G., Bu, X.-Z., and Cai, S.-H. (2013). Epithelial\u2013Mesenchymal Transition (EMT) Induced by TNF-\u03b1 Requires AKT\/GSK-3\u03b2-Mediated Stabilization of Snail in Colorectal Cancer. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0056664"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"29047","DOI":"10.18632\/oncotarget.25540","article-title":"Oral inflammation promotes oral squamous cell carcinoma invasion","volume":"9","author":"Goertzen","year":"2018","journal-title":"Oncotarget"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.identj.2024.06.014","article-title":"Blocking \u03b22-AR and Inhibiting COX-2: A Promising Approach to Suppress OSCC Development","volume":"75","author":"Huang","year":"2025","journal-title":"Int. Dent. J."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Condurache Hri\u021bcu, O.M., Costan, V.-V., Toader, \u0218.V., Ciobanu Apostol, D.G., Solcan, C., Br\u0103ni\u0219teanu, D.E., and Toader, M.P. (2025). The Inflammatory\u2013Dysplastic Spectrum in Oral Lichen Planus: A Study on Six Immunohistochemical Markers. Diagnostics, 15.","DOI":"10.3390\/diagnostics15192443"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"84","DOI":"10.14715\/cmb\/2023.69.9.12","article-title":"The expression of Th17\/Treg in oral submucosal fibrosis carcinogenesis and the significance in the development of mucosal lesions","volume":"69","author":"Dan","year":"2023","journal-title":"Cell. Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"339","DOI":"10.3233\/CBM-203092","article-title":"Targeting IL-17alpha to promote anti-PD-1 therapy effect by screening the tumor immune microenvironment in a mouse oral carcinogenesis model","volume":"31","author":"Wang","year":"2021","journal-title":"Cancer Biomark."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ladjevac, N., Milovanovic, M., Jevtovic, A., Arsenijevic, D., Stojanovic, B., Dimitrijevic Stojanovic, M., Stojanovic, B., Arsenijevic, N., Arsenijevic, A., and Milovanovic, J. (2023). The Role of IL-17 in the Pathogenesis of Oral Squamous Cell Carcinoma. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24129874"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00432-025-06296-6","article-title":"PPAR\u03b3 accelerates OSCC progression via Th17 polarization and CEBPA\/IL-17C signaling","volume":"151","author":"Wang","year":"2025","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Li, J., Ji, W.-T., Chen, H.-R., Lin, C.-H., Lee, J.-W., and Lee, C.-C. (2014). Monocyte Chemotactic Protein 1 (MCP-1) Modulates Pro-Survival Signaling to Promote Progression of Head and Neck Squamous Cell Carcinoma. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088952"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/j.freeradbiomed.2010.09.006","article-title":"Oxidative stress, inflammation, and cancer: How are they linked?","volume":"49","author":"Reuter","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1136\/gut.2004.047100","article-title":"Prostaglandins and Cancer","volume":"55","author":"Wang","year":"2006","journal-title":"Gut"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s00784-015-1506-4","article-title":"Salivary 8-hydroxy-2-deoxyguanosine, malondialdehyde, vitamin C, and vitamin E in oral pre-cancer and cancer: Diagnostic value and free radical mechanism of action","volume":"20","author":"Kaur","year":"2015","journal-title":"Clin. Oral Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1177\/0192623309356453","article-title":"Oxidative Stress and Oxidative Damage in Carcinogenesis","volume":"38","author":"Klaunig","year":"2009","journal-title":"Toxicol. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1023\/A:1007934229968","article-title":"Oxidative Stress and Cancer: The Role of Redox Regulation","volume":"11","author":"Toyokuni","year":"1998","journal-title":"Biotherapy"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbi.2005.12.009","article-title":"Free radicals, metals and antioxidants in oxidative stress-induced cancer","volume":"160","author":"Valko","year":"2006","journal-title":"Chem.-Biol. Interact."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.cell.2010.03.015","article-title":"Matrix Metalloproteinases: Regulators of the Tumor Microenvironment","volume":"141","author":"Kessenbrock","year":"2010","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s10555-011-9335-7","article-title":"Potential molecular targets for inhibiting bone invasion by oral squamous cell carcinoma: A review of mechanisms","volume":"31","author":"Quan","year":"2011","journal-title":"Cancer Metastasis Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nrc2544","article-title":"A tense situation: Forcing tumour progression","volume":"9","author":"Butcher","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1101\/gad.1909210","article-title":"The Hippo\u2013YAP pathway in organ size control and tumorigenesis: An updated version","volume":"24","author":"Zhao","year":"2010","journal-title":"Genes Dev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1002\/ijc.25429","article-title":"Regulatory T cells in tumor immunity","volume":"127","author":"Nishikawa","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Mori, K., Haraguchi, S., Hiori, M., Shimada, J., and Ohmori, Y. (2015). Tumor-associated macrophages in oral premalignant lesions coexpress CD163 and STAT1 in a Th1-dominated microenvironment. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1587-0"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nri1995","article-title":"Crosstalk between cancer and immune cells: Role of STAT3 in the tumour microenvironment","volume":"7","author":"Yu","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","article-title":"Epithelial-Mesenchymal Transitions in Development and Disease","volume":"139","author":"Thiery","year":"2009","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"43684","DOI":"10.1038\/s41598-025-27447-2","article-title":"Integrated profiling reveals polarity protein dysregulation during oral cancer progression","volume":"15","author":"Ghose","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_56","first-page":"127","article-title":"TWIST1 regulates proliferation, migration, and invasion and is a prognostic marker for oral tongue squamous cell carcinoma","volume":"52","author":"Barboza","year":"2022","journal-title":"J. Oral Pathol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41598-025-87790-2","article-title":"Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis","volume":"15","author":"Shetty","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nrm2083","article-title":"Integrating cell-signalling pathways with NF-\u03baB and IKK function","volume":"8","author":"Perkins","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/ni0302-221","article-title":"NF-\u03baB at the crossroads of life and death","volume":"3","author":"Karin","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S1359-6101(00)00018-6","article-title":"NF-\u03baB and cell-cycle regulation: The cyclin connection","volume":"12","author":"Joyce","year":"2001","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1093\/nar\/28.3.669","article-title":"Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT)","volume":"28","author":"Kyo","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1056\/NEJM199704103361506","article-title":"Nuclear Factor-\u03baB\u2014A Pivotal Transcription Factor in Chronic Inflammatory Diseases","volume":"336","author":"Barnes","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature04870","article-title":"Nuclear factor-\u03baB in cancer development and progression","volume":"441","author":"Karin","year":"2006","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/jcb.21695","article-title":"NF-\u03baB and epithelial to mesenchymal transition of cancer","volume":"104","author":"Min","year":"2008","journal-title":"J. Cell. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Wang, Y., Liu, Y., Du, W., Xue, J., Ruan, J., Yu, J., Ma, B., and Li, X. (2026). Interventional effects of mesenchymal stem cells on epithelial\u2013mesenchymal transition in head and neck squamous cell carcinoma and underlying mechanisms: A systematic review and meta-analysis of in vitro studies. Front. Immunol., 16, Correction in Front. Immunol. 2026, 17, 1786161. https:\/\/doi.org\/10.3389\/fimmu.2026.1786161.","DOI":"10.3389\/fimmu.2026.1786161"},{"key":"ref_66","first-page":"e31164","article-title":"Up-regulation of TNF-alpha\/NFkB\/SIRT1 axis drives aggressiveness and cancer stem cells accumulation in chemoresistant oral squamous cell carcinoma","volume":"239","author":"Milan","year":"2023","journal-title":"J. Cell. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.4317\/medoral.20570","article-title":"Expression of NF-\u03baB and IL-6 in oral precancerous and cancerous lesions: An immunohistochemical study","volume":"50","author":"Kamperos","year":"2016","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.oraloncology.2014.02.004","article-title":"Inhibitors of NF-kappaB reverse cellular invasion and target gene upregulation in an experimental model of aggressive oral squamous cell carcinoma","volume":"50","author":"Johnson","year":"2014","journal-title":"Oral Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Babiuch, K., Ku\u015bnierz-Cabala, B., K\u0119sek, B., Oko\u0144, K., Darczuk, D., and Chomyszyn-Gajewska, M. (2020). Evaluation of Proinflammatory, NF-kappaB Dependent Cytokines: IL-1\u03b1, IL-6, IL-8, and TNF-\u03b1 in Tissue Specimens and Saliva of Patients with Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030867"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"103945","DOI":"10.1016\/j.identj.2025.103945","article-title":"TTK Defines a High-Risk Oral Squamous Cell Carcinoma Subtype Through Dual mTORC1\/NF-\u03baB Activation","volume":"75","author":"Jin","year":"2025","journal-title":"Int. Dent. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/odi.12623","article-title":"Evaluation of the p-AKT, p-JNK and FoxO3a function in oral epithelial dysplasia","volume":"23","author":"Chaves","year":"2017","journal-title":"Oral Dis."},{"key":"ref_72","first-page":"721","article-title":"Quantitative cell-cycle protein expression in oral cancer assessed by computer-assisted system","volume":"21","author":"Soares","year":"2006","journal-title":"Histol. Histopathol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"102986","DOI":"10.1016\/j.critrevonc.2020.102986","article-title":"Oral potentially malignant disorders: A scoping review of prognostic biomarkers","volume":"153","author":"Mello","year":"2020","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/nrc2734","article-title":"STATs in cancer inflammation and immunity: A leading role for STAT3","volume":"9","author":"Yu","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cytogfr.2009.11.005","article-title":"Dangerous liaisons: STAT3 and NF-\u03baB collaboration and crosstalk in cancer","volume":"21","author":"Grivennikov","year":"2010","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0092-8674(00)81959-5","article-title":"Stat3 as an Oncogene","volume":"98","author":"Bromberg","year":"1999","journal-title":"Cell"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1158\/1078-0432.CCR-04-1752","article-title":"Persistent Activation of Stat3 Signaling Induces Survivin Gene Expression and Confers Resistance to Apoptosis in Human Breast Cancer Cells","volume":"12","author":"Gritsko","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1038\/sj.onc.1205260","article-title":"Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis","volume":"21","author":"Niu","year":"2002","journal-title":"Oncogene"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/j.oraloncology.2012.06.006","article-title":"Targeting STAT3 inhibits growth and enhances radiosensitivity in head and neck squamous cell carcinoma","volume":"48","author":"Adachi","year":"2012","journal-title":"Oral Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1038\/nm1325","article-title":"Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity","volume":"11","author":"Kortylewski","year":"2005","journal-title":"Nat. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5819","DOI":"10.1074\/jbc.M111.295964","article-title":"Roles of STAT3 and ZEB1 Proteins in E-cadherin Down-regulation and Human Colorectal Cancer Epithelial-Mesenchymal Transition","volume":"287","author":"Xiong","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.cell.2017.10.044","article-title":"Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer","volume":"171","author":"Puram","year":"2017","journal-title":"Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.ccr.2009.02.015","article-title":"Persistently Activated Stat3 Maintains Constitutive NF-\u03baB Activity in Tumors","volume":"15","author":"Lee","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/cr.2010.183","article-title":"NF-\u03baB and STAT3\u2014Key players in liver inflammation and cancer","volume":"21","author":"He","year":"2010","journal-title":"Cell Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nrc2809","article-title":"Eicosanoids and cancer","volume":"10","author":"Wang","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/1-4020-5688-5_4","article-title":"Cyclooxygenase-2 (cox-2) and the inflammogenesis of cancer","volume":"42","author":"Harris","year":"2007","journal-title":"Subcell. Biochem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nrc2069","article-title":"G-protein-coupled receptors and cancer","volume":"7","author":"Dorsam","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S0092-8674(00)81433-6","article-title":"Cyclooxygenase Regulates Angiogenesis Induced by Colon Cancer Cells","volume":"93","author":"Tsujii","year":"1998","journal-title":"Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"5211","DOI":"10.1158\/0008-5472.CAN-05-0141","article-title":"Tumor cyclooxygenase-2\/prostaglandin E2-dependent promotion of FOXP3 expression and CD4+ CD25+ T regulatory cell activities in lung cancer","volume":"65","author":"Sharma","year":"2005","journal-title":"Cancer Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5338","DOI":"10.1158\/0008-5472.CAN-05-3635","article-title":"Cyclooxygenase-2-dependent regulation of E-cadherin: Prostaglandin E(2) induces transcriptional repressors ZEB1 and snail in non-small cell lung cancer","volume":"66","author":"Dohadwala","year":"2006","journal-title":"Cancer Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1126\/science.1116221","article-title":"Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis","volume":"310","author":"Castellone","year":"2005","journal-title":"Science"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"9409","DOI":"10.1073\/pnas.0902367106","article-title":"15-Hydroxyprostaglandin dehydrogenase inactivation as a mechanism of resistance to celecoxib chemoprevention of colon tumors","volume":"106","author":"Yan","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"99066","DOI":"10.18632\/oncotarget.21524","article-title":"Nonsteroidal anti-inflammatory drugs using and risk of head and neck cancer: A dose-response meta analysis of prospective cohort studies","volume":"8","author":"Shi","year":"2017","journal-title":"Oncotarget"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1001\/archotol.132.11.1231","article-title":"Chemoprevention of head and neck cancer with aspirin: A case-control study","volume":"132","author":"Jayaprakash","year":"2006","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1007\/s00432-010-0837-4","article-title":"Circulating cycloxygenase-2 in patients with tobacco-related intraoral squamous cell carcinoma and evaluation of its peptide inhibitors as potential antitumor agent","volume":"136","author":"Kapoor","year":"2010","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1146\/annurev.med.57.121304.131253","article-title":"NSAIDs and cancer prevention: Targets downstream of COX-2","volume":"58","author":"Cha","year":"2007","journal-title":"Annu. Rev. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.oraloncology.2017.07.015","article-title":"Nomogram for risk prediction of malignant transformation in oral leukoplakia patients using combined biomarkers","volume":"72","author":"Zhang","year":"2017","journal-title":"Oral Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.oraloncology.2007.10.006","article-title":"Polymorphisms of COX-2 -765G>C and p53 codon 72 and risks of oral squamous cell carcinoma in a Taiwan population","volume":"44","author":"Lin","year":"2008","journal-title":"Oral Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Karen-Ng, L.P., Ahmad, U.S., Gomes, L., Hunter, K.D., Wan, H., Hagi-Pavli, E., and Parkinson, E.K. (2022). Extracellular Prostaglandins E1 and E2 and Inflammatory Cytokines Are Regulated by the Senescence Program in Potentially Premalignant Oral Keratinocytes. Cancers, 14.","DOI":"10.1101\/2022.03.10.483769"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1200\/jco.2005.23.16_suppl.1025","article-title":"Pilot study of celecoxib in oral premalignant lesions (OPLs): Preliminary results","volume":"23","author":"Wirth","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1158\/1078-0432.CCR-07-4024","article-title":"Pilot Randomized Phase II Study of Celecoxib in Oral Premalignant Lesions","volume":"14","author":"Papadimitrakopoulou","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1056\/NEJMoa050405","article-title":"Cardiovascular Risk Associated with Celecoxib in a Clinical Trial for Colorectal Adenoma Prevention","volume":"352","author":"Solomon","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.4103\/jpbs.JPBS_109_17","article-title":"Oral Field Cancerization and Its Clinical Implications in the Management in Potentially Malignant Disorders","volume":"9","author":"Sathiasekar","year":"2017","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.oooo.2015.12.018","article-title":"Oral submucous fibrosis: Review on mechanisms of malignant transformation","volume":"122","author":"Ekanayaka","year":"2016","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1111\/odi.13727","article-title":"Malignant transformation of oral submucous fibrosis: A systematic review and meta-analysis","volume":"27","author":"Kujan","year":"2020","journal-title":"Oral Dis."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Khan, I., Kumar, N., Pant, I., Narra, S., and Kondaiah, P. (2012). Activation of TGF-beta pathway by areca nut constituents: A possible cause of oral submucous fibrosis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051806"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.4317\/medoral.18226","article-title":"Expression of transforming growth factor beta and its correlation with lipodystrophy in oral submucous fibrosis: An immunohistochemical study","volume":"18","author":"Kale","year":"2013","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mrrev.2016.10.002","article-title":"A systematic review and meta-analysis of the association between long non-coding RNA polymorphisms and cancer risk","volume":"771","author":"Lv","year":"2017","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"5787","DOI":"10.2147\/JIR.S337014","article-title":"Long Non-Coding RNAs in Oral Submucous Fibrosis: Their Functional Mechanisms and Recent Research Progress","volume":"14","author":"He","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.2353\/ajpath.2007.070112","article-title":"The myofibroblast: One function, multiple origins","volume":"170","author":"Hinz","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/j.1600-0714.2010.00995.x","article-title":"Evaluation of myofibroblasts in oral submucous fibrosis: Correlation with disease severity","volume":"40","author":"Angadi","year":"2011","journal-title":"J. Oral Pathol. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"314","DOI":"10.4103\/1735-3327.215960","article-title":"Evaluation of myofibroblasts in oral submucous fibrosis and oral squamous cell carcinoma: The pathogenesis and correlation","volume":"14","author":"Gandhi","year":"2017","journal-title":"Dent. Res. J."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Hernandez, B.Y., Zhu, X., Goodman, M.T., Gatewood, R., Mendiola, P., Quinata, K., and Paulino, Y.C. (2017). Betel nut chewing, oral premalignant lesions, and the oral microbiome. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172196"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1111\/j.1600-0714.2012.01172.x","article-title":"Oxidative stress status and DNA damage in saliva of human subjects with oral lichen planus and oral squamous cell carcinoma","volume":"41","author":"Farmanbar","year":"2012","journal-title":"J. Oral Pathol. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.archoralbio.2019.03.021","article-title":"Role of autophagy induced by arecoline in angiogenesis of oral submucous fibrosis","volume":"102","author":"Dai","year":"2019","journal-title":"Arch. Oral Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"184","DOI":"10.2334\/josnusd.19-0170","article-title":"Role of autophagy and apoptosis in atrophic epithelium in oral submucous fibrosis","volume":"62","author":"Zhu","year":"2020","journal-title":"J. Oral Sci."},{"key":"ref_117","first-page":"3041","article-title":"Effect of autophagy-associated proteins on the arecoline-induced liver injury in mice","volume":"16","author":"Wang","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1080\/15384101.2022.2040932","article-title":"Improvement of autophagic flux mediates the protection of hydrogen sulfide against arecoline-elicited neurotoxicity in PC12 cells","volume":"21","author":"Gao","year":"2022","journal-title":"Cell Cycle"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/jop.12924","article-title":"Oral submucous fibrosis in Asian countries","volume":"49","author":"Peng","year":"2020","journal-title":"J. Oral Pathol. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/sj.cdd.4401373","article-title":"Roles of CHOP\/GADD153 in endoplasmic reticulum stress","volume":"11","author":"Oyadomari","year":"2004","journal-title":"Cell Death Differ."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/j.1600-0714.2007.00582.x","article-title":"Nomenclature and classification of potentially malignant disorders of the oral mucosa","volume":"36","author":"Warnakulasuriya","year":"2007","journal-title":"J. Oral Pathol. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"7","DOI":"10.4103\/0970-9371.76941","article-title":"Micronuclei: An essential biomarker in oral exfoliated cells for grading of oral squamous cell carcinoma","volume":"28","author":"Jadhav","year":"2011","journal-title":"J. Cytol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/bjc.1996.62","article-title":"LOH at 3p correlates with a poor survival in oral squamous cell carcinoma","volume":"73","author":"Partridge","year":"1996","journal-title":"Br. J. Cancer"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/gcc.20064","article-title":"Chromosomal instability and marker chromosome evolution in oral squamous cell carcinoma","volume":"41","author":"Reshmi","year":"2004","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Cabral, L.G.S., Martins, I.M., Paulo, E.P.A., Pomini, K.T., Poyet, J.L., and Maria, D.A. (2025). Molecular Mechanisms in the Carcinogenesis of Oral Squamous Cell Carcinoma: A Literature Review. Biomolecules, 15.","DOI":"10.3390\/biom15050621"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1007\/s12253-019-00700-6","article-title":"Expression of hTERT in Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma\u2014An Immunohistochemical Analysis","volume":"26","author":"Raju","year":"2020","journal-title":"Pathol. Oncol. Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"362","DOI":"10.4103\/0970-9290.84281","article-title":"Immunohistochemical detection of human telomerase reverse transcriptase in oral cancer and pre-cancer","volume":"22","author":"Palani","year":"2011","journal-title":"Indian J. Dent. Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.1002\/hed.27540","article-title":"TERT promoter mutation positive oral cavity carcinomas, a clinically and genetically distinct subgroup of head and neck squamous cell carcinomas","volume":"45","author":"Saito","year":"2023","journal-title":"Head Neck"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1111\/apm.12723","article-title":"The methylation status and expression of human telomerase reverse transcriptase is significantly high in oral carcinogenesis","volume":"125","author":"Haraguchi","year":"2017","journal-title":"APMIS"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/j.1600-0714.1999.tb02109.x","article-title":"Telomerase activity and in situ telomerase RNA expression in oral carcinogenesis","volume":"28","author":"Chang","year":"1999","journal-title":"J. Oral Pathol. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.pharmthera.2004.01.002","article-title":"Signaling through the epidermal growth factor receptor during the development of malignancy","volume":"102","author":"Grandis","year":"2004","journal-title":"Pharmacol. Ther."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1056\/NEJMoa073770","article-title":"TP53 mutations and survival in squamous-cell carcinoma of the head and neck","volume":"357","author":"Poeta","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"797","DOI":"10.4103\/0970-9290.152208","article-title":"Promoter hypermethylation patterns of P16, DAPK and MGMT in oral squamous cell carcinoma: A systematic review and meta-analysis","volume":"25","author":"Don","year":"2014","journal-title":"Indian J. Dent. Res."},{"key":"ref_134","first-page":"2253","article-title":"MicroRNA-9 enhances invasion and migration of cervical carcinomas by directly targeting FOXO1","volume":"22","author":"Aishanjiang","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.cell.2004.06.006","article-title":"Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis","volume":"117","author":"Yang","year":"2004","journal-title":"Cell"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.cell.2008.03.027","article-title":"The epithelial-mesenchymal transition generates cells with properties of stem cells","volume":"133","author":"Mani","year":"2008","journal-title":"Cell"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"105164","DOI":"10.1016\/j.archoralbio.2021.105164","article-title":"Role of Yes-associated protein and transcriptional coactivator with PDZ-binding motif in the malignant transformation of oral submucous fibrosis","volume":"128","author":"Sharma","year":"2021","journal-title":"Arch. Oral Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00418-025-02360-x","article-title":"FAK mediates mechanical signaling to maintain epithelial homeostasis through YAP\/TAZ-TEADs","volume":"163","author":"Peng","year":"2025","journal-title":"Histochem. Cell Biol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s12929-022-00824-z","article-title":"MicroRNA-485-5p targets keratin 17 to regulate oral cancer stemness and chemoresistance via the integrin\/FAK\/Src\/ERK\/beta-catenin pathway","volume":"29","author":"Jang","year":"2022","journal-title":"J. Biomed. Sci."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.cell.2009.10.027","article-title":"Matrix crosslinking forces tumor progression by enhancing integrin signaling","volume":"139","author":"Levental","year":"2009","journal-title":"Cell"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s10555-011-9340-x","article-title":"Cancer-associated-fibroblasts and tumour cells: A diabolic liaison driving cancer progression","volume":"31","author":"Cirri","year":"2012","journal-title":"Cancer Metastasis Rev."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/S0002-9440(10)64255-1","article-title":"Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis","volume":"161","author":"Schoppmann","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41591-018-0014-x","article-title":"Understanding the tumor immune microenvironment (TIME) for effective therapy","volume":"24","author":"Binnewies","year":"2018","journal-title":"Nat. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"e218","DOI":"10.1016\/S1470-2045(12)70582-X","article-title":"Cytokine patterns in patients with cancer: A systematic review","volume":"14","author":"Lippitz","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Weber, M., Lutz, R., Olmos, M., Glajzer, J., Baran, C., Nobis, C.-P., M\u00f6st, T., Eckstein, M., Kesting, M., and Ries, J. (2022). Beyond PD-L1\u2014Identification of Further Potential Therapeutic Targets in Oral Cancer. Cancers, 14.","DOI":"10.3390\/cancers14071812"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature07205","article-title":"Cancer-related inflammation","volume":"454","author":"Mantovani","year":"2008","journal-title":"Nature"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Sutera, S., Furchi, O.A., and Pentenero, M. (2025). Macrophages and the immune microenvironment in OPMDs: A systematic review of the literature. Front. Oral Health, 6.","DOI":"10.3389\/froh.2025.1605978"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Zhao, S., Zhang, Y., Meng, X., Wang, Y., Li, Y., Li, H., Zhao, X., Yang, P., Liu, S., and Yang, C. (2025). INHBA(+) macrophages and Pro-inflammatory CAFs are associated with distinctive immunosuppressive tumor microenvironment in submucous Fibrosis-Derived oral squamous cell carcinoma. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-14261-2"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.oraloncology.2019.07.012","article-title":"Malignant transformation risk of oral lichen planus: A systematic review and comprehensive meta-analysis","volume":"96","author":"Ayen","year":"2019","journal-title":"Oral Oncol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.oooo.2016.03.011","article-title":"Etiology and pathogenesis of oral lichen planus: An overview","volume":"122","author":"Kurago","year":"2016","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"127","DOI":"10.4103\/0973-029X.84474","article-title":"Oral lichen planus: An update on pathogenesis and treatment","volume":"15","author":"Lavanya","year":"2011","journal-title":"J. Oral Maxillofac. Pathol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1177\/154411130201300405","article-title":"The pathogenesis of oral lichen planus","volume":"13","author":"Sugerman","year":"2002","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41421-023-00532-4","article-title":"Single-cell and spatial dissection of precancerous lesions underlying the initiation process of oral squamous cell carcinoma","volume":"9","author":"Sun","year":"2023","journal-title":"Cell Discov."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/1348-0421.12232","article-title":"Analysis of oral microbial community and Th17-associated cytokines in saliva of patients with oral lichen planus","volume":"59","author":"Wang","year":"2015","journal-title":"Microbiol. Immunol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ajpath.2012.03.044","article-title":"Th17 cells: Biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies","volume":"181","author":"Maddur","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1007\/s10753-013-9594-2","article-title":"Interaction between oral lichen planus and chronic periodontitis with Th17-associated cytokines in serum","volume":"36","author":"Wang","year":"2013","journal-title":"Inflammation"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1007\/s10753-009-9118-2","article-title":"IFN-gamma and IL-4 in saliva of patients with oral lichen planus: A study in an ethnic Chinese population","volume":"32","author":"Liu","year":"2009","journal-title":"Inflammation"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1600-0714.2006.00402.x","article-title":"Expression profile of chemokines and chemokine receptors in epithelial cell layers of oral lichen planus","volume":"35","author":"Ichimura","year":"2006","journal-title":"J. Oral Pathol. Med."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/j.1600-0714.2011.01084.x","article-title":"Altered expression of miR-21, miR-125b, and miR-203 indicates a role for these microRNAs in oral lichen planus","volume":"41","author":"Danielsson","year":"2012","journal-title":"J. Oral Pathol. Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.molimm.2014.06.037","article-title":"Microbe- and danger-induced inflammation","volume":"63","author":"Broggi","year":"2015","journal-title":"Mol. Immunol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1159\/000099585","article-title":"CD4+CD25high regulatory T cells are markedly decreased in blood of patients with pemphigus vulgaris","volume":"214","author":"Sugiyama","year":"2007","journal-title":"Dermatology"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Kim, T.-J., Kim, Y.G., Jung, W., Jang, S., Ko, H.-G., Park, C.H., Byun, J.-S., and Kim, D.-Y. (2023). Non-Coding RNAs as Potential Targets for Diagnosis and Treatment of Oral Lichen Planus: A Narrative Review. Biomolecules, 13.","DOI":"10.3390\/biom13111646"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"105761","DOI":"10.1016\/j.intimp.2019.105761","article-title":"Long non-coding RNA DQ786243 modulates the induction and function of CD4+ Treg cells through Foxp3-miR-146a-NF-\u03baB axis: Implications for alleviating oral lichen planus","volume":"75","author":"Wang","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s10020-021-00382-4","article-title":"Deregulation of circ_003912 contributes to pathogenesis of erosive oral lichen planus by via sponging microRNA-123, -647 and -31 and upregulating FOXP3","volume":"27","author":"Huang","year":"2021","journal-title":"Mol. Med."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/ijc.28754","article-title":"Potentially malignant disorders of the oral cavity: Current practice and future directions in the clinic and laboratory","volume":"136","author":"Dionne","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.oraloncology.2008.05.016","article-title":"Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management","volume":"45","year":"2009","journal-title":"Oral Oncol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1111\/odi.12065","article-title":"Urban legends series: Oral leukoplakia","volume":"19","author":"Arduino","year":"2013","journal-title":"Oral Dis."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1034\/j.1600-0714.2002.00042.x","article-title":"Analysis of the Ki-67 antigen at the invasive tumour front of human oral squamous cell carcinoma","volume":"31","author":"Tumuluri","year":"2002","journal-title":"J. Oral Pathol. Med."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1002\/cncr.22386","article-title":"Salivary analysis in oral cancer patients: DNA and protein oxidation, reactive nitrogen species, and antioxidant profile","volume":"109","author":"Bahar","year":"2007","journal-title":"Cancer"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1073\/pnas.0610117104","article-title":"Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma","volume":"104","author":"Prince","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1593\/neo.06274","article-title":"Molecular cross-talk between the NFkappaB and STAT3 signaling pathways in head and neck squamous cell carcinoma","volume":"8","author":"Squarize","year":"2006","journal-title":"Neoplasia"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"103037","DOI":"10.1016\/j.tice.2025.103037","article-title":"The small GTP-binding Ras-like protein DIRAS2 promotes cell proliferation in oral leukoplakia via the RAF\/MEK\/MAPK pathway","volume":"96","author":"Li","year":"2025","journal-title":"Tissue Cell"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/s41419-026-08580-w","article-title":"Histone lactylation-driven feedback loop modulates pyrimidine metabolism to promote oral carcinogenesis","volume":"17","author":"Wang","year":"2026","journal-title":"Cell Death Dis."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"102531","DOI":"10.1016\/j.tranon.2025.102531","article-title":"FAP promotes progression of oral leukoplakia via activation of PI3K\/AKT pathway by interacting with ITGB1","volume":"61","author":"Li","year":"2025","journal-title":"Transl. Oncol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s40246-016-0063-5","article-title":"Human genome meeting 2016: Houston, TX, USA. 28 February\u20132 March 2016","volume":"10","author":"Srivastava","year":"2016","journal-title":"Hum. Genom."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"5546","DOI":"10.1038\/s41467-019-13471-0","article-title":"Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4","volume":"10","author":"Wang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_177","first-page":"CD010276","article-title":"Diagnostic tests for oral cancer and potentially malignant disorders in patients presenting with clinically evident lesions","volume":"7","author":"Walsh","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1158\/1940-6207.CAPR-10-0155","article-title":"Gene expression profiling predicts the development of oral cancer","volume":"4","author":"Saintigny","year":"2011","journal-title":"Cancer Prev. Res."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"7907","DOI":"10.1007\/s13277-015-4694-2","article-title":"TERT promoter hot spot mutations are frequent in Indian cervical and oral squamous cell carcinomas","volume":"37","author":"Vinothkumar","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrc.2018.11","article-title":"The molecular landscape of head and neck cancer","volume":"18","author":"Leemans","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S1470-2045(05)70540-4","article-title":"Promoter methylation and inactivation of tumour-suppressor genes in oral squamous-cell carcinoma","volume":"7","author":"Ha","year":"2006","journal-title":"Lancet Oncol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"e77","DOI":"10.4317\/medoral.24975","article-title":"MicroRNAs and their role in the malignant transformation of oral leukoplakia: A scoping review","volume":"27","author":"Niklander","year":"2022","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.oraloncology.2015.11.017","article-title":"MicroRNA-31 upregulation predicts increased risk of progression of oral potentially malignant disorder","volume":"53","author":"Hung","year":"2016","journal-title":"Oral Oncol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.21037\/atm-20-3840","article-title":"Comprehensive analysis of circular RNA in oral leukoplakia: Upregulated circHLA-C as a potential biomarker for diagnosis and prognosis","volume":"8","author":"Xu","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1002\/hed.21315","article-title":"Single-marker identification of head and neck squamous cell carcinoma cancer stem cells with aldehyde dehydrogenase","volume":"32","author":"Clay","year":"2010","journal-title":"Head Neck"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1053\/j.seminoncol.2014.03.003","article-title":"Tumor microenvironment in head and neck squamous cell carcinoma","volume":"41","author":"Curry","year":"2014","journal-title":"Semin. Oncol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrclinonc.2016.60","article-title":"Cancer metabolism: A therapeutic perspective","volume":"14","author":"Pestell","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1158\/1055-9965.EPI-07-2867","article-title":"p16 Promoter Methylation Is a Potential Predictor of Malignant Transformation in Oral Epithelial Dysplasia","volume":"17","author":"Hall","year":"2008","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Dey, S., Biswas, B., Manoj Appadan, A., Shah, J., Pal, J., Basu, S., and Sur, S. (2023). Non-Coding RNAs in Oral Cancer: Emerging Roles and Clinical Applications. Cancers, 15.","DOI":"10.3390\/cancers15153752"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.ebiom.2015.03.015","article-title":"P16 Methylation as an Early Predictor for Cancer Development from Oral Epithelial Dysplasia: A Double-blind Multicentre Prospective Study","volume":"2","author":"Liu","year":"2015","journal-title":"eBioMedicine"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1111\/odi.13115","article-title":"Histone modifications in oral squamous cell carcinoma and oral potentially malignant disorders","volume":"26","author":"Yang","year":"2019","journal-title":"Oral Dis."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1186\/s13059-024-03383-8","article-title":"Multi-omics reveals lactylation-driven regulatory mechanisms promoting tumor progression in oral squamous cell carcinoma","volume":"25","author":"Jing","year":"2024","journal-title":"Genome Biol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"535","DOI":"10.3892\/ijmm.2020.4628","article-title":"Long non-coding RNAs are novel players in oral inflammatory disorders, potentially premalignant oral epithelial lesions and oral squamous cell carcinoma (Review)","volume":"46","author":"Zhang","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.oraloncology.2008.07.011","article-title":"Dysregulated molecular networks in head and neck carcinogenesis","volume":"45","author":"Molinolo","year":"2009","journal-title":"Oral Oncol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.adaj.2017.07.032","article-title":"Evidence-based clinical practice guideline for the evaluation of potentially malignant disorders in the oral cavity","volume":"148","author":"Lingen","year":"2017","journal-title":"J. Am. Dent. Assoc."},{"key":"ref_196","first-page":"CD001829","article-title":"Interventions for treating oral leukoplakia to prevent oral cancer","volume":"2016","author":"Lodi","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1111\/odi.13980","article-title":"Management of oral potentially malignant disorders","volume":"27","author":"Kerr","year":"2021","journal-title":"Oral Dis."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"105110","DOI":"10.1016\/j.oraloncology.2020.105110","article-title":"UK consensus recommendations on the management of oral epithelial dysplasia during COVID-19 pandemic outbreaks","volume":"112","author":"McCarthy","year":"2021","journal-title":"Oral Oncol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/j.1601-0825.2006.01349.x","article-title":"Molecular genetics of premalignant oral lesions","volume":"13","author":"Mithani","year":"2007","journal-title":"Oral Dis."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/jop.12339","article-title":"Malignant transformation of oral leukoplakia: A systematic review of observational studies","volume":"45","author":"Warnakulasuriya","year":"2016","journal-title":"J. Oral Pathol. Med."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"106481","DOI":"10.1016\/j.oraloncology.2023.106481","article-title":"Molecular screening of head neck cancer","volume":"144","author":"Mali","year":"2023","journal-title":"Oral Oncol."},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Khong, B., Ferlito, S., Quek, S., Conte, G., Ingrassia, A., Lechien, J.R., Chiesa-Estomba, C., Mayo, M., Maniaci, A., and Radulesco, T. (Ear Nose Throat J., 2024). Past, Present, and Future Diagnostic Methods for the Early Noninvasive Detection of Oral Premalignant Lesions: A State of the Art and Systematic Review, Ear Nose Throat J., ahead of print.","DOI":"10.1177\/01455613241245204"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"14036","DOI":"10.1038\/s41598-018-32441-y","article-title":"Pretreatment Identification of Head and Neck Cancer Nodal Metastasis and Extranodal Extension Using Deep Learning Neural Networks","volume":"8","author":"Kann","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1158\/1940-6207.CAPR-12-0173","article-title":"Loss of Heterozygosity (LOH) Profiles\u2014Validated Risk Predictors for Progression to Oral Cancer","volume":"5","author":"Zhang","year":"2012","journal-title":"Cancer Prev. Res."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"96604","DOI":"10.18632\/oncotarget.21852","article-title":"Circulating betatrophin is associated with insulin resistance in humans: Cross-sectional and interventional studies in vivo and in vitro","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_206","doi-asserted-by":"crossref","unstructured":"(1994). Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group. The Effect of Vitamin E and Beta Carotene on the Incidence of Lung Cancer and Other Cancers in Male Smokers. N. Engl. J. Med., 330, 1029\u20131035.","DOI":"10.1056\/NEJM199404143301501"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1056\/NEJM199605023341802","article-title":"Effects of a Combination of Beta Carotene and Vitamin A on Lung Cancer and Cardiovascular Disease","volume":"334","author":"Omenn","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"e18492","DOI":"10.7717\/peerj.18492","article-title":"Evaluating the efficacy of curcumin in the management of oral potentially malignant disorders: A systematic review and meta-analysis","volume":"12","author":"Shi","year":"2024","journal-title":"PeerJ"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/joim.12476","article-title":"Immune dysregulation mediated by the oral microbiome: Potential link to chronic inflammation and atherosclerosis","volume":"280","author":"Slocum","year":"2016","journal-title":"J. Intern. Med."},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Herreros-Pomares, A., Herv\u00e1s, D., Bagan-Deb\u00f3n, L., Jantus-Lewintre, E., Gimeno-Cardona, C., and Bagan, J. (2023). On the Oral Microbiome of Oral Potentially Malignant and Malignant Disorders: Dysbiosis, Loss of Diversity, and Pathogens Enrichment. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043466"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1158\/1940-6207.CAPR-09-0121","article-title":"Phase II Randomized, Placebo-Controlled Trial of Green Tea Extract in Patients with High-Risk Oral Premalignant Lesions","volume":"2","author":"Tsao","year":"2009","journal-title":"Cancer Prev. Res."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41522-025-00688-9","article-title":"Probiotics and prebiotics: New treatment strategies for oral potentially malignant disorders and gastrointestinal precancerous lesions","volume":"11","author":"Huang","year":"2025","journal-title":"npj Biofilms Microbiomes"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1158\/1078-0432.CCR-13-3159","article-title":"Topical Application of a Mucoadhesive Freeze-Dried Black Raspberry Gel Induces Clinical and Histologic Regression and Reduces Loss of Heterozygosity Events in Premalignant Oral Intraepithelial Lesions: Results from a Multicentered, Placebo-Controlled Clinical Trial","volume":"20","author":"Mallery","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"101899","DOI":"10.1016\/j.jebdp.2023.101899","article-title":"Clinical Efficacy of Photodynamic Therapy in Management of Oral Potentially Malignant Disorders: A Systematic Review and Meta-Analysis","volume":"24","author":"Silva","year":"2024","journal-title":"J. Evid. Based Dent. Pr."},{"key":"ref_215","doi-asserted-by":"crossref","unstructured":"Wang, Y., Tang, H., Wang, K., Zhao, Y., Xu, J., and Fan, Y. (2024). Clinical evaluation of photodynamic therapy for oral leukoplakia: A retrospective study of 50 patients. BMC Oral Health, 24.","DOI":"10.1186\/s12903-023-03791-5"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"104850","DOI":"10.1016\/j.oraloncology.2020.104850","article-title":"Laser excision of oral leukoplakia: Does it affect recurrence and malignant transformation? A systematic review and meta-analysis","volume":"109","author":"Migliorati","year":"2020","journal-title":"Oral Oncol."},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"Zhang, R., Gao, T., and Wang, D. (2023). Photodynamic therapy (PDT) for oral leukoplakia: A systematic review and meta-analysis of single-arm studies examining efficacy and subgroup analyses. BMC Oral Health, 23.","DOI":"10.1186\/s12903-023-03294-3"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.pdpdt.2019.08.005","article-title":"Photodynamic therapy for oral potentially malignant disorders","volume":"28","author":"Jin","year":"2019","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.pdpdt.2018.10.023","article-title":"Photodynamic therapy in the treatment of oral leukoplakia: A systematic review","volume":"25","author":"Li","year":"2019","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_220","first-page":"250","article-title":"Photodynamic therapy of cancer: An update","volume":"61","author":"Agostinis","year":"2011","journal-title":"CA Cancer J. Clin."},{"key":"ref_221","doi-asserted-by":"crossref","unstructured":"Kruczek-Kazibudzka, A., Lipka, B., Fiegler-Rudol, J., Tkaczyk, M., Skaba, D., and Wiench, R. (2025). Toluidine Blue and Chlorin-e6 Mediated Photodynamic Therapy in the Treatment of Oral Potentially Malignant Disorders: A Systematic Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26062528"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1158\/1535-7163.MCT-17-0646","article-title":"Matrix Metalloproteinase Inhibitors in Cancer Therapy: Turning Past Failures into Future Successes","volume":"17","author":"Winer","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_223","doi-asserted-by":"crossref","unstructured":"Guo, Y., Xu, T., Chai, Y., and Chen, F. (2023). TGF-\u03b2 Signaling in Progression of Oral Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210263"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1158\/1940-6207.CAPR-09-0163","article-title":"Epidermal Growth Factor Receptor Expression and Gene Copy Number in the Risk of Oral Cancer","volume":"3","author":"Saintigny","year":"2010","journal-title":"Cancer Prev. Res."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1001\/jamaoncol.2015.4364","article-title":"Erlotinib and the Risk of Oral Cancer","volume":"2","author":"William","year":"2016","journal-title":"JAMA Oncol."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"17022","DOI":"10.1038\/cddiscovery.2017.22","article-title":"In silico analysis of pathways activation landscape in oral squamous cell carcinoma and oral leukoplakia","volume":"3","author":"Makarev","year":"2017","journal-title":"Cell Death Discov."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.tripleo.2010.11.018","article-title":"Increased subepithelial vascularization and VEGF expression reveal potentially malignant changes in human oral mucosa lesions","volume":"111","author":"Gandolfo","year":"2011","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endodontology"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"e147096","DOI":"10.1172\/jci.insight.147096","article-title":"Inhibition of mTOR signaling and clinical activity of metformin in oral premalignant lesions","volume":"6","author":"Gutkind","year":"2021","journal-title":"JCI Insight"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1056\/NEJMoa053422","article-title":"Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck","volume":"354","author":"Bonner","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_230","doi-asserted-by":"crossref","unstructured":"Jiang, Q., Xiao, J., Hsieh, Y.-C., Kumar, N.L., Han, L., Zou, Y., and Li, H. (2024). The Role of the PI3K\/Akt\/mTOR Axis in Head and Neck Squamous Cell Carcinoma. Biomedicines, 12.","DOI":"10.3390\/biomedicines12071610"},{"key":"ref_231","doi-asserted-by":"crossref","unstructured":"Ali, A., Molska, G.R., Yeo, H., Esfandiari, N., Jeong, W., Huang, M., and Magalhaes, M. (2025). Immune Microenvironment in Oral Potentially Malignant Disorders and Oral Cancer: A Narrative Review. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202501.0149.v1"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"3293","DOI":"10.1200\/JCO.2015.61.1509","article-title":"Immunology and Immunotherapy of Head and Neck Cancer","volume":"33","author":"Ferris","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"106986","DOI":"10.1016\/j.oraloncology.2024.106986","article-title":"Localized intratumoral delivery of immunomodulators for oral cancer and oral potentially malignant disorders","volume":"158","author":"Hussein","year":"2024","journal-title":"Oral Oncol."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1056\/NEJMoa1602252","article-title":"Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck","volume":"375","author":"Ferris","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/S0140-6736(19)32591-7","article-title":"Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): A randomised, open-label, phase 3 study","volume":"394","author":"Burtness","year":"2019","journal-title":"Lancet"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1084\/jem.20082683","article-title":"STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing","volume":"206","author":"Pickert","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cytogfr.2016.05.001","article-title":"STAT3 signaling in immunity","volume":"31","author":"Hillmer","year":"2016","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1111\/odi.13797","article-title":"Aneuploidy and loss of heterozygosity as risk markers for malignant transformation in oral mucosa","volume":"27","author":"Odell","year":"2021","journal-title":"Oral Dis."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.oooo.2022.07.006","article-title":"Clinical predictors of malignant transformation and recurrence in oral potentially malignant disorders: A systematic review and meta-analysis","volume":"134","author":"Paglioni","year":"2022","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_240","doi-asserted-by":"crossref","unstructured":"Palaia, G., Bellisario, A., Pampena, R., Pippi, R., and Romeo, U. (2021). Oral Proliferative Verrucous Leukoplakia: Progression to Malignancy and Clinical Implications. Systematic Review and Meta-Analysis. Cancers, 13.","DOI":"10.3390\/cancers13164085"},{"key":"ref_241","doi-asserted-by":"crossref","unstructured":"Mesgari, H., Esmaelian, S., Nasiri, K., Ghasemzadeh, S., Doroudgar, P., and Payandeh, Z. (2023). Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review. Cancers, 15.","DOI":"10.3390\/cancers15235600"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"505","DOI":"10.4155\/fmc.12.3","article-title":"Targeted Cancer Therapy: Giving Histone Deacetylase Inhibitors All They Need to Succeed","volume":"4","author":"Gryder","year":"2012","journal-title":"Future Med. Chem."},{"key":"ref_243","doi-asserted-by":"crossref","unstructured":"Umapathy, V.R., Natarajan, P.M., and Swamikannu, B. (2024). Molecular and Therapeutic Roles of Non-Coding RNAs in Oral Cancer\u2014A Review. Molecules, 29.","DOI":"10.3390\/molecules29102402"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5632\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:38:02Z","timestamp":1782272282000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5632"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,22]]},"references-count":243,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27125632"],"URL":"https:\/\/doi.org\/10.3390\/ijms27125632","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,22]]}}}