Locally advanced head and neck squamous cell carcinomas (HNSCC) have very limited
prognosis due to frequent treatment failure and recurrence. Currently TNM-classification
and human papillomavirus (HPV) infection are the sole clinical prognosticators of
outcome. Tumor heterogeneity based on epithelial-mesenchymal-transition reportedly
associates with therapy resistance of carcinomas. Therefore, expression of epithelial
marker EpCAM (EpEX), reprogramming factor Sox2 and mesenchymal marker vimentin were
assessed in a discovery cohort of HNSCC patients treated with surgery and adjuvant
radio(chemo)therapy (n = 94). Expression of all three markers was heterogeneous in
HNSCC. EpEX(high) and Sox2(high) predicted enhanced overall, disease-free and disease-specific
survival in the entire cohort and, importantly, in the HPV-negative subgroup of the
discovery cohort. Sox2(high) and EpEX(high) were confirmed as prognosticators in a
validation cohort of HNSCC patients treated with definitive radio(chemo)therapy (n
= 94). However, only EpEX(high) allowed identification of patients with improved survival
endpoints within the HPV-negative subgroup of the validation cohort. Hence, Sox2(high)
and particularly EpEX(high) have potential as tools for the prediction of clinical
performance of HNSCC patients, foremost HPV-negative cases, in the frame of molecular-guided
treatment decision-making.
