Rachel Galot

Presentation
Circulating tumor DNA (ctDNA) has emerged as a promising non-invasive biomarker across multiple tumor types, with applications ranging from early detection to treatment response monitoring and surveillance. In head and neck squamous cell carcinoma (HNSCC), the majority of research and clinical development has focused on HPV-positive disease, leveraging the presence of viral DNA as a highly specific and sensitive target. However, for the more biologically heterogeneous and prognostically poorer HPV-negative subset, the clinical utility of ctDNA remains less clearly defined.

This presentation will critically evaluate the current evidence supporting the use of ctDNA in HPV-negative HNSCC, focusing on key areas such as minimal residual disease (MRD) detection, early relapse identification, and response-adaptive therapy strategies.

Emerging prospective data and proof-of-concept studies suggest that ctDNA may have prognostic value in HPV-negative disease, correlating with risk of recurrence. However, many challenges remain before ctDNA can be integrated into routine clinical practice in this setting. These include defining the optimal gene panels, assay timing, clinical thresholds for actionability, and demonstrating impact on clinical outcomes in well-powered trials.

We will discuss ongoing and planned clinical studies aiming to validate ctDNA as a tool for treatment personalization—such escalation in high-risk patients identified via molecular surveillance.

This session aims to answer the question: Is ctDNA ready for prime time in HPV-negative HNSCC? While the answer may still be evolving, the growing body of evidence indicates that ctDNA holds significant potential, and integration into clinical trials is a crucial next step.