A Meta-Analysis and Systematic Review of the Frequency, Clinicopathological Features, and Diagnostic Potential of CDH1 Methylation in Head and Neck Cancer

INTRODUCTION: Head and neck cancer (HNC), particularly head and neck squamous cell carcinoma (HNSCC), is a major global health issue. Epigenetic alterations, especially the hypermethylation of tumor suppressor genes (TSGs) such as CDH1, which encodes the E-cadherin protein, play a crucial role in the development and progression of HNC. This meta-analysis aimed to evaluate the role of CDH1 methylation as a potential diagnostic and less invasive biomarker for HNC, assessing its correlation with various clinical, pathological, and lifestyle factors, including tumor size, lymph node involvement, clinical stage, smoking, and alcohol consumption. METHODS: A systematic search was conducted across multiple databases (PubMed, Scopus, Web of Science, and Cochrane Library) up to September 2024. Studies that reported the frequency of CDH1 methylation in HNC patients and its association with clinicopathological factors were included. Statistical analysis was performed using Review Manager (RevMan 5.4) software, and diagnostic test accuracy (DTA) was assessed through sensitivity, specificity, and area under the curve (AUC) analyses using MetaDesk software. RESULTS: Forty-three studies, involving 1542 HNC patients and 1532 controls, were included. The pooled analysis showed a significantly higher prevalence of CDH1 methylation in HNC patients compared to controls (OR = 8.09, 95% CI: 5.29-12.36, P < 0.001). Subgroup analysis revealed significant associations in both Asian and Caucasian populations and various tumor subtypes. CDH1 methylation correlated with alcohol consumption and advanced clinical stage, but not with tumor size, lymph node involvement, or metastatic status. The pooled diagnostic odds ratio was 8.18 (95% CI: 5.32-12.58), with an AUC of 0.78, indicating moderate diagnostic accuracy. CONCLUSION: CDH1 methylation holds promise as a diagnostic biomarker for HNC, demonstrating high specificity but moderate sensitivity. While its association with specific clinicopathological factors is notable, it should be used in conjunction with other diagnostic tools for more effective clinical application.