In the early stage of HNCs with no lymph node metastasis, we found that higher expression of caspase-8 alone or in combination with higher DR5 expression significantly correlated with better disease-free survival and overall survival [46], suggesting an inhibitory role of DR5/caspase-8 signaling in the regulation of cancer development and progression. This evidence concerns the gene TNFRSF10B and metastatic malignant neoplasm in the lymph nodes.