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

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.