Postoperative circulating tumor DNA (ctDNA) may predict recurrence risk in HPV-negative head and neck squamous cell carcinoma, according to a meta-analysis of eight studies. Detectable ctDNA after surgery was associated with a roughly ten-fold elevated recurrence risk. The authors caution that sensitivity analyses suggest limitations, underscoring the need for careful interpretation and standardized testing workflows before routine adoption. Still, the signal strengthens the case for using postoperative ctDNA as a practical stratification tool in a high-recurrence subgroup. For trial designers, these results support refining risk-adapted adjuvant strategies based on measurable molecular residual disease rather than solely pathologic factors.