Stratifying HNSCC patient data from TCGA into ‘CD109 high/IL6Rα high’ versus ‘CD109 low/IL6Rα low’ reveals worse disease-specific and overall survival (OS) probabilities in ‘CD109 high/IL6Rα high’ patients, suggesting the potential of CD109/IL6Rα co-expression as a prognostic signature for SCC progression. Here, IL6R is linked to head and neck squamous cell carcinoma.