Prognostic and Clinicopathological Significance of Epidermal Growth Factor Receptor (EGFR) Expression in Oral Squamous Cell Carcinoma: Systematic Review and Meta-Analysis

Abstract

The aim of this systematic review and meta-analysis was to evaluate the current evidence in relation to the clinicopathological and prognostic significance of epidermal growth factor receptor (EGFR) overexpression in patients with oral squamous cell carcinoma (OSCC). We searched MEDLINE/PubMed, Embase, Web of Science, and Scopus for studies published before November 2022. We evaluated the quality of primary-level studies using the QUIPS tool, conducted meta-analyses, examined inter-study heterogeneity via subgroup analyses and meta-regressions, and performed small-study effects analyses. Fifty primary-level studies (4631 patients) met the inclusion criteria. EGFR overexpression was significantly associated with poor overall survival (hazard ratio [HR] = 1.38, 95% confidence intervals [CI] = 1.06-1.79, p = 0.02), N+ status (odds ratio [OR] = 1.37, 95%CI = 1.01-1.86, p = 0.04), and moderately-poorly differentiated OSCC (OR = 1.43, 95% CI = 1.05-1.94, p = 0.02). In addition, better results were obtained by the application of a cutoff point ≥10% tumor cells with EGFR overexpression (p < 0.001). In conclusion, our systematic review and meta-analysis supports that the immunohistochemical assessment of EGFR overexpression may be useful as a prognostic biomarker for OSCC.

Keywords: EGFR; epidermal growth factor receptor; meta-analysis; oral cancer; prognosis; systematic review.

Figure 1

Flow diagram showing the identification and selection process of relevant studies, analyzing the prognostic and clinicopathological significance of EGFR overexpression in OSCC.

Figure 2

Quality plot graphically representing the risk of bias (RoB) across primary-level studies using a method specifically designed for systematic reviews and meta-analyses addressing questions on prognostic factor studies (i.e., Quality in Prognosis Studies -QUIPS- tool, developed by members of the Cochrane Prognosis Methods Group [68]). The following domains (D1–D6) were critically judged: D1, study participation; D2, study attrition; D3, prognostic factor measurement; D4, outcome measurement; D5, study confounding; and D6, statistical analysis/reporting. RoB was assessed for all domains throughout all studies and scored as potentially low (depicted as green color), moderate (yellow color), or high (red color) [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67].

Figure 3

Forest plot graphically representing the meta-analysis on the association between EGFR overexpression and OS in patients with OSCC. Random-effects model, inverse-variance weighting (based on the DerSimonian and Laird method). A HR > 1 suggests that EGFR overexpression is associated with poor prognosis. Diamonds indicate the pooled HRs with their corresponding 95%CIs. Abbreviations: EGFR, epidermal growth factor receptor; OS, overall survival; OSCC, oral squamous cell carcinoma; HR, hazard ratio; CI, confidence intervals [19,23,24,25,28,34,40,42,43,45,48,51,53,55,56,59,65,66,67].