Reliability of gene-expression profiling from tumor biopsy for refining neoadjuvant strategies in patients with head and neck squamous cell carcinoma

•Targeted gene-expression profiles of paired TB and SRS are highly correlated.•A perfect clustering of paired TB and SRS occurred in 52–64% of patients.•Immune-related pathways are stable across TB and SRS samples. While recent clinical trials evaluating neoadjuvant immune checkpoint inhibitors showed promising results in a subset of patients with head and neck squamous cell carcinomas (HNSCC), there is a need for the identification of robust biomarkers in tumor biopsies to improve patient selection. This context suggests unravelling transcriptomic heterogeneity between untreated paired samples from same patient with HNSCC. Based on previous studies and the analysis of publicly available gene expression profiles of paired tumor biopsies and surgical resection specimens, we discuss the reliability of tumor biopsy to capture the overall activation of targetable biological pathways in patients with HNSCC. Further studies investigating intratumor transcriptomic heterogeneity as well as the effect of sampling methods on gene expression are needed in patients with HNSCC, in order to develop innovative and relevant biomarker-driven neoadjuvant strategies.