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<p>Despite advances in multimodal therapy, survival in advanced head and neck squamous cell carcinoma (HNSCC) has improved only modestly. Tumor-informed circulating tumor DNA (ctDNA) assays allow early detection of molecular residual disease (MRD) and recurrence after curative treatment. We analyzed ctDNA in plasma from 76 and saliva from 54 HNSCC patients before and after curative-intent surgery, testing 656 plasma and 128 saliva samples longitudinally. High preoperative ctDNA shedding correlated with advanced pathological stage, lymph node involvement, adverse histologic features, and molecular markers including PD-1 expression and tumor mutational burden. Transcriptomic profiling showed associations between high shedding and increased proliferation, EGFR/MAPK pathway activity, and upregulation of EGFR-related invasion and metastasis genes. Plasma ctDNA detected ≥14 days post-surgery identified 91.3% of recurrences, with lead times up to 500 days before clinical confirmation. These results highlight the value of serial ctDNA monitoring for early relapse detection and potentially improved treatment guidance in HNSCC.</p>

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Personalized ctDNA analysis for detection of residual disease and recurrence in surgically treated HNSCC patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月3日

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  • Susanne Flach,
  • Christodoulos Pipinikas,
  • Tom Huberty,
  • Axel Lechner,
  • Clodagh Murray,
  • Giovanni Marsico,
  • Karen Howarth,
  • Christoph Walz,
  • Lukas Käsmann,
  • Andreas Mock,
  • Philipp Jurmeister,
  • Kristian Unger,
  • Sophia Stöcklein,
  • Gizem Abaci,
  • Nitzan Rosenfeld,
  • Christoph A. Reichel,
  • Olivier Gires,
  • Martin Canis,
  • Philipp Baumeister

摘要

Despite advances in multimodal therapy, survival in advanced head and neck squamous cell carcinoma (HNSCC) has improved only modestly. Tumor-informed circulating tumor DNA (ctDNA) assays allow early detection of molecular residual disease (MRD) and recurrence after curative treatment. We analyzed ctDNA in plasma from 76 and saliva from 54 HNSCC patients before and after curative-intent surgery, testing 656 plasma and 128 saliva samples longitudinally. High preoperative ctDNA shedding correlated with advanced pathological stage, lymph node involvement, adverse histologic features, and molecular markers including PD-1 expression and tumor mutational burden. Transcriptomic profiling showed associations between high shedding and increased proliferation, EGFR/MAPK pathway activity, and upregulation of EGFR-related invasion and metastasis genes. Plasma ctDNA detected ≥14 days post-surgery identified 91.3% of recurrences, with lead times up to 500 days before clinical confirmation. These results highlight the value of serial ctDNA monitoring for early relapse detection and potentially improved treatment guidance in HNSCC.