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SYSTEMATIC REVIEW article
Front. Oral. Health
Sec. Oral Cancers
Volume 6 - 2025 | doi: 10.3389/froh.2025.1578561
This article is part of the Research Topic Advances and Innovative Discoveries in Oral Potentially Malignant Disorders View all 5 articles
Significance of Epidermal Growth Factor Receptor (EGFR) upregulation in the prediction of the malignant transformation risk in oral potentially malignant disorders: A systematic review and metaanalysis
Provisionally accepted- School of Dentistry, University of Granada. Biohealth Research Institute, Ibs.Granada, Spain, Granada, Spain
The purpose of this systematic review and meta-analysis was to appraise, both quantitatively and qualitatively, the extant evidence regarding the role of EGFR upregulation in predicting malignant transformation risk associated with oral potentially malignant disorders (OPMD). A comprehensive search was undertaken in the Web of Science, Embase, MEDLINE (via PubMed), and Scopus databases for longitudinal primary-level articles, whether prospective or retrospective in design, without restrictions on language or publication date. The QUIPS tool was employed for the purpose of assessing the potential for bias. A meta-analysis was conducted in addition to sensitivity analyses and analyses of the potential influence of small-study effects. In total, eight studies, which were treated as nine distinct units for analytical purposes, were included in the final sample, which encompassed 653 patients with OPMD with follow-up data. EGFR upregulation was found to be significantly associated with an elevated malignant transformation risk of OPMD (RR = 2.17, 95%CI = 1.73 -2.73, p < 0.001). Subgroup analyses demonstrated that both EGFR protein overexpression (RR = 2.02, 95%CI = 1.55 -2.63, p < 0.001) and EGFR gene amplification (RR = 2.70, 95%CI = 1.72 -4.25, p < 0.001), nuclear staining (RR = 3.47, 95%CI = 1.50 -8.01, p = 0.004) and the >10% cutoff point were significantly associated with transformation risk (RR = 2.27, 95%CI = 1.33 -3.87, p = 0.003). In conclusion, the present systematic review and meta-analysis evidence-based demonstrates that EGFR overexpression, assessed through immunohistochemical technique, behaves functions as a risk marker of OPMD malignant transformation risk.
Keywords: EGFR, epidermal growth factor receptor, Oral potentially malignant disorders, Oral leukoplakia, malignant transformation, oral cancer, Systematic review, Meta-analysis
Received: 17 Feb 2025; Accepted: 14 Mar 2025.
Copyright: © 2025 Civico-Ortega, Ramos-Garcia and Gonzalez-Moles. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Pablo Ramos-Garcia, School of Dentistry, University of Granada. Biohealth Research Institute, Ibs.Granada, Spain, Granada, Spain
Miguel Angel Gonzalez-Moles, School of Dentistry, University of Granada. Biohealth Research Institute, Ibs.Granada, Spain, Granada, Spain
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