EGFR and TP53 mutations linked to worse survival in sinonasal squamous cell carcinomaGenetic markers linked to survival in sinonasal squamous cell carcinoma

This meta-analysis, comprising 25 retrospective cohort studies with a total of 1194 patients diagnosed with sinonasal squamous cell carcinoma (SNSCC), evaluated the prognostic significance of various genetic and molecular alterations. The median follow-up was 33 months. The study assessed associations between overall survival (OS) and disease-free survival (DFS) and alterations including EGFR mutation, TP53 mutation, EGFR copy number gain, DEK::AFF2 alteration, and expression of EGFR, p53, Foxp3, SOX2, KMT2D, PD-L1, and Bax.

Primary outcomes were OS at 2, 3, 5, and 10 years and DFS at 1 and 3 years. EGFR mutation was associated with worse OS at all time points, with hazard ratios (HRs) of 1.57, 1.49, 1.41, and 1.32, respectively. For DFS, EGFR mutation yielded HRs of 3.70 at 1 year and 1.51 at 3 years. TP53 mutation was also linked to worse OS, with HRs of 3.54, 3.33, and 2.70 at 2, 3, and 5 years. EGFR copy number gain was associated with worse 5-year OS (HR 1.59). PD-L1 expression was associated with worse 3-year OS (HR 1.43). EGFR overexpression was associated with higher regional recurrence (HR 2.69).

Conversely, Foxp3 expression was associated with improved OS at 2, 3, and 5 years (HRs 0.42, 0.51, and 0.53) and improved DFS at 2, 3, and 5 years (HRs 0.48, 0.48, and 0.50). SOX2, Bax, p53 overexpression, and KMT2D expression were not significantly associated with prognosis. No safety data were reported, as this was a prognostic factor meta-analysis.

These results align with prior evidence implicating EGFR and TP53 in head and neck cancers, but this meta-analysis specifically quantifies their impact in SNSCC. The finding that Foxp3 expression is associated with better survival is novel and may reflect an immune-mediated protective effect. However, the analysis is limited by the retrospective nature of included studies, potential heterogeneity in assays and thresholds, and lack of reported confidence intervals or p-values for the hazard ratios. Additionally, the absence of multivariable adjustment in many studies raises the possibility of confounding.

Clinically, these findings suggest that molecular profiling, particularly for EGFR and TP53 mutations and Foxp3 expression, may help stratify prognosis in SNSCC patients. However, prospective validation is needed before these markers can be used to guide treatment decisions. Unanswered questions include the optimal cutoff values for expression markers, the role of combined alterations, and whether these associations are independent of known clinical risk factors.