A recent study combined differential methylation data with clinical information to develop predictive risk score (RS) signatures based on methylation sites in overall HNSCC, such as a novel four-gene methylation signature (ZNF10, TMPRSS12, ERGIC2, and RNF215) associated with differential survival outcomes in HNSCC patients undergoing radiotherapy [85]; however, they were unable to develop separate scores based on HPV status. Here, RNF215 is linked to head and neck squamous cell carcinoma.