ArticleThe journal of liquid biopsy2026
Prognostic utility of copy number variations in circulating tumor DNA in head and neck cancer.
Article in The journal of liquid biopsy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Plasma circulating tumor DNA (ctDNA) is a minimally invasive biomarker in head and neck squamous cell carcinoma (HNSCC). Most commercially available assays for human papillomavirus-unrelated HNSCC are tumor-informed assays that require tissue sampling and may not comprehensively capture tumor heterogeneity. We evaluated a tumor-agnostic approach using genome-wide ctDNA copy-number variation (CNV) profiling to derive blood copy-number burden (CNB) for prognostication in non-surgically treated HNSCC. Methods: ctDNA was extracted from 250 longitudinal plasma samples from 33 patients and analyzed using PredicineSCORE low-pass whole-genome sequencing (LP-WGS). CNB was dichotomized as positive (CNB+) or negative (CNB-) using a predefined threshold. Associations with overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier models. Results: Median age was 63 years; 67% were male; 67% had recurrent/metastatic disease; 15% were HPV-associated. Treatment included chemoradiation (39%) and immune checkpoint blockade-based regimens (60%). The most frequent CNV was 3q gain. Baseline plasma was available for 30 patients, of whom 17 (56%) were CNB+. Baseline CNB+ was associated with inferior OS (HR 4.38, 95% CI 1.22-15.72; p = 0.01) but not PFS (HR 1.41, 95% CI 0.62-3.20; p = 0.41) over a median follow-up of 23.4 months. CNB + at any post-treatment timepoint occurred in 26/33 (79%) and showed a non-significant trend toward worse OS (HR 3.03; p = 0.12) and PFS (HR 2.70; p = 0.06). Detection rates were modest, highlighting potential utility mainly in CNV-high, HPV-independent tumors over time. Conclusions: LP-WGS enables tumor-agnostic detection of CNV signals in plasma from non-surgically treated HNSCC, and baseline CNB stratifies OS. Larger, more homogeneous cohorts with matched tumor sequencing are needed to validate ctDNA-derived CNV metrics and define which molecular subtypes benefit most from blood-based CNB detection and monitoring. Level of evidence: 3.
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