Promoter hypermethylation of TIMP3 detected in pretreatment salivary rinse ctDNA of HNSCC patients is associated with disease-free survival; even if without tumor site differentiation, hypermethylation of TIMP3 can be considered a salivary independent prognostic factor of HNSCC recurrence, including OSCC. The gene discussed is TIMP3; the disease is head and neck squamous cell carcinoma.