Journal: NPJ precision oncology
This study evaluated a tumor-informed circulating tumor DNA (ctDNA) assay as a tool for molecular residual disease (MRD) and recurrence detection in head and neck squamous cell carcinoma (HNSCC) treated with curative-intent surgery.
Key points:
- Cohort and sampling:
- Plasma ctDNA was analyzed in 76 patients; saliva ctDNA in 54 patients.
- Longitudinal testing included 656 plasma and 128 saliva samples collected before and after surgery.
- Baseline ctDNA shedding:
- High preoperative ctDNA shedding correlated with:
- More advanced pathological stage.
- Lymph node involvement.
- Adverse histologic features.
- Higher PD-1 expression and increased tumor mutational burden.
- Transcriptomic analysis of high-shedding tumors showed:
- Increased proliferative signaling.
- Elevated EGFR/MAPK pathway activity.
- Upregulation of EGFR-associated genes linked to invasion and metastasis.
- High preoperative ctDNA shedding correlated with:
- Postoperative surveillance and recurrence:
- Detection of plasma ctDNA at least 14 days after surgery identified 91.3% of patients who later recurred.
- ctDNA often preceded clinical or radiographic relapse, with lead times up to 500 days.
- Implications:
- Serial, tumor-informed ctDNA monitoring in plasma (and to a lesser extent saliva) provides sensitive early detection of molecular relapse after surgery in HNSCC.
- ctDNA shedding reflects underlying aggressive biology and may inform risk stratification.
- These findings support integrating ctDNA-based MRD assessment into postoperative surveillance and potentially treatment decision-making in HNSCC.