External validation of prognostic and predictive gene signatures in head and neck cancer patients

Head and neck squamous cell carcinomas (HNSCC) are aggressive and heterogenous tumors with a high fatality rate. Many gene signatures (GS) have been developed with both prognostic and predictive significance. We aimed to externally validate five published GS in a large European collection of HNSCC patients. Gene expression from 1097 treatment-naïve HNSCC patients’ primary tumors was used to calculate scores for the five GS. Cox proportional hazard models were used to test the association between both 2-year overall survival and 2-year disease-free survival and the signature scores. The predictive role of GS was validated by comparing survival associations in patients receiving specific treatment (i.e., radiotherapy, systemic treatment) versus those who did not. We successfully externally validated all 5 GS, including two prognostic signatures, one signature as prognostic and predictive of sensitivity to systemic treatment, while signatures for cisplatin-sensitivity and radiosensitivity were validated as prognostic only.