Worldwide prevalence of PI3K-AKT-mTOR pathway mutations in head and neck cancer: A systematic review and meta-analysis

A systematic review (SR) and meta-analysis were conducted to determine the prevalence of PI3K-AKT-mTOR signaling pathway mutations in patients with head and neck cancer (HNC). Overall, 105 studies comprising 8630 patients and 1306 mutations were selected. The estimated mutations prevalence was 13 % for PIK3CA (95 % confidence interval [CI] = 11-14; I-2 = 82 %; p < 0.0001), 4% for PTEN (95 % CI = 3-5; I-2 = 55 %; p < 0.0001), 3% for MTOR (95 % CI = 2-4; I-2 = 5%; p = 0.40), and 2% for AKT (95 % CI = 1-2; I-2 = 50 %; p = 0.0001). We further stratified the available data of the participants according to risk factors and tumor characteristics, including HPV infection, tobacco use, alcohol exposure, TNM stage, and histological tumor differentiation, and performed subgroup analysis. We identified significant associations between PI3K-AKT-mTOR pathway-associated mutations and advanced TNM stage (odds ratio [OR] = 0.20; 95 % CI = 0.09-0.44; I-2 = 71 %; p = 0.0001) and oropharyngeal HPV-positive tumors and PIK3CA mutations (OR = 17.48; 95 % CI = 4.20-72.76; I-2 = 69 %; p < 0.0002). No associations were found between alcohol and tobacco exposure, and tumor differentiation grade. This SR demonstrated that the PI3K-AKT-mTOR pathway emerges as a potential prognostic factor and could offer a molecular basis for future studies on therapeutic targeting in HNC patients.

Automated summary

The systematic review and meta-analysis examined the prevalence of PI3K-AKT-mTOR pathway mutations in head and neck cancer patients, identifying significant associations with advanced TNM stage and oropharyngeal HPV-positive tumors. Different mutation rates were found for genes like PIK3CA and PTEN, showing relevance to tumor characteristics and risk factors. The study suggests that these mutations could serve as potential prognostic factors and may guide future therapeutic targeting in HNC patients.