Worldwide Prevalence and Clinical Characteristics of RAS Mutations in Head and Neck Cancer: A Systematic Review and Meta-Analysis

In light of the development of RAS inhibitors, a reliable assessment of the prevalence of RAS mutations and their correlation with the clinical features of patients with HNC is crucially needed. This meta-analysis compiles the findings of 149 studies with over 8500 HNC patients and assesses the global prevalence of mutations in the HRAS, KRAS and NRAS genes. The available data were stratified according to geographical region, clinical features, and tumor characteristics, including human papillomavirus (HPV) infection status and tumor stage. In addition, the distribution of codon substitutions in each RAS gene was assessed. The estimated mutation rate is highest for HRAS (7%), followed by KRAS (2.89%) and NRAS (2.20%). HRAS prevalence in South Asia (15.28%) is twice as high as the global estimate. HRAS mutations are more prevalent in oral cavity and salivary gland tumors. In contrast, KRAS mutations are found more frequently in sinonasal tumors, and NRAS mutations are found chiefly in tumors of the nasopharynx. OR analyses show a significant association between HRAS mutations and a high tumor stage (OR=3.63). In addition, there is a significant association between HPV-positive status and KRAS mutations (OR=2.09). This study highlights RAS as a potential therapeutic target in certain subsets of HNC patients.