Impact of Genetic and Molecular Alterations on Clinical Outcomes in Sinonasal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

Background: Sinonasal squamous cell carcinoma (SNSCC) is a rare malignancy with variable outcomes, and the prognostic impact of molecular alterations remains incompletely defined. This meta-analysis aims to clarify the associations of genetic alterations and protein expression with clinical outcomes in SNSCC. Methods: PubMed, Embase, Web of Science, and ScienceDirect were searched from inception through February 2026. Eligible studies reported prognostic outcomes in SNSCC according to EGFR mutation, TP53 mutation, EGFR copy number gain, EGFR-associated progression from inverted papilloma to SNSCC, DEK::AFF2 alteration, or expression of EGFR, p53, Foxp3, SOX2, KMT2D, PD-L1, and Bax. Random-effects models were used to pool survival or recurrence rates and hazard ratios (HRs) with 95% confidence intervals. Results: Of 689 records, 25 retrospective cohort studies including at least 1194 patients with SNSCC were analyzed. Median age was 63.8 years, 69.7% were male, and median follow-up was 33 months. EGFR mutation was associated with worse overall survival (OS) at 2, 3, 5, and 10 years (HRs 1.57, 1.49, 1.41, and 1.32, respectively) and worse disease-free survival (DFS) at 1 and 3 years (HRs 3.70 and 1.51). TP53 mutation was associated with worse OS at 2, 3, and 5 years (HRs 3.54, 3.33, and 2.70). EGFR copy number gain was associated with worse 5-year OS (HR 1.59), EGFR overexpression with higher regional recurrence (HR 2.69), and PD-L1 expression with worse 3-year OS (HR 1.43). In contrast, Foxp3 expression was associated with improved 2-, 3-, and 5-year OS (HRs 0.42, 0.51, and 0.53) and DFS (HRs 0.48, 0.48, and 0.50). Other biomarkers, such as SOX2, Bax, p53 overexpression, and KMT2D expression, were not significantly associated with prognosis. Conclusion: Molecular profiling has prognostic value in SNSCC. EGFR and TP53 alterations were associated with poorer outcomes, whereas Foxp3 expression was associated with more favorable survival, supporting further biomarker-integrated risk stratification in SNSCC.