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 meta-analysis Cívico Ortega, José Luis Ramos García, Pablo González Moles, Miguel Ángel EGFR Epidermal growth factor receptor Oral potentially malignant disorders The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors. The Supplementary Material for this article can be found online https://www.frontiersin.org/articles/10.3389/froh. 2025.1578561/full#supplementary-material Objectives: 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). Methods: 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. Results: 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). Conclusion: The present systematic review and meta-analysis demonstrates that EGFR overexpression, assessed through immunohistochemical technique, functions as a risk marker of OPMD malignant transformation risk. 2025-05-26T11:08:27Z 2025-05-26T11:08:27Z 27-03-27 journal article Cívico-Ortega JL, Ramos-García P and González-Moles MÁ (2025) 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 meta-analysis. Front. Oral Health 6:1578561. [doi: 10.3389/froh.2025.1578561] https://hdl.handle.net/10481/104259 10.3389/froh.2025.1578561 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional Frontiers Media