In HNSCC, it was revealed that SFRP1 and SFRP5 were methylated in OSCC patients who like chewing betel quid, while this was not observed in normal oral mucosa and precancerous lesions, suggesting that methylation changes were specific and sensitive to the carcinogenesis of OSCC [14]. The gene discussed is SFRP5; the disease is head and neck squamous cell carcinoma.