BackgroundTraditional imaging and pathological examinations lack sufficient sensitivity for detecting minimal residual disease (MRD), limiting early identification of subclinical recurrence in head and neck squamous cell carcinoma (HNSCC).Aims/objectivesTo explore the clinical utility of dynamic circulating tumor DNA (ctDNA) monitoring in detecting MRD after surgery for locally advanced HNSCC.Material and methodsSixteen patients with locally advanced HNSCC who underwent radical treatment were enrolled. Peripheral blood samples were collected preoperatively and one week to five years postoperatively for ctDNA analysis. Tumor tissue targeted sequencing and clinicopathological parameters were integrated to evaluate the sensitivity, specificity, and prognostic value of MRD detection.ResultsThe preoperative ctDNA positivity rate was 81.3% (13/16), with a median content of 22.6 hGE/ml (range: 0.45-131.92). High-frequency genetic alterations included TP53 mutations (81.3%, 13/16), with hotspot mutations such as p.R273C, p.H193L, and p.R342. Copy number reduction in CDKN2A (43.8%, 7/16) and PIK3CA mutations (18.8%, 3/16) were the main driver alterations. One patient with hypopharyngeal carcinoma (T3N2bM0) tested ctDNA-positive 1.5 months postoperatively, which was 6.5 months earlier than radiological recurrence (tongue metastasis detected 8 months postoperatively).Conclusions and significanceDynamic ctDNA monitoring effectively identifies postoperative MRD in HNSCC. (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(MRD)(sic)(sic)(sic)(sic)(sic)(sic), (sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(HNSCC)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)DNA(ctDNA)(sic)(sic)(sic)(sic)(sic)(sic)(sic)HNSCC(sic)(sic)(sic)(sic)MRD(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)(sic)16(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)HNSCC(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)1(sic)(sic)5(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)ctDNA(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic), (sic)(sic)MRD(sic)(sic)(sic)(sic)(sic)(sic),(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).(sic)(sic)(sic)(sic)ctDNA(sic)(sic)(sic)(sic)81.3%(13/16), (sic)(sic)(sic)(sic)(sic)22.6 hGE/ml((sic)(sic): 0.45-131.92).(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)TP53(sic)(sic)(81.3%, 13/16), (sic)(sic)(sic)(sic)(sic)(sic)p.R273C,p.H193L(sic)p.R342.CDKN2A(sic)(sic)(sic)(sic)(sic)(43.8%, 7/16)(sic)PIK3CA(sic)(sic)(18.8%, 3/16)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic).1(sic)(sic)(sic)(sic)(T3N2bM0)(sic)(sic)(sic)(sic)1.5(sic)(sic)(sic)(sic)ctDNA(sic)(sic), (sic)(sic)(sic)(sic)(sic)((sic)(sic)8(sic)(sic)(sic)(sic)(sic)(sic)(sic))(sic)6.5(sic)(sic).(sic)(sic)(sic)(sic)(sic)(sic)(sic)ctDNA(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(HNSCC)(sic)(sic)MRD.