Integrating Immunotherapy Into Head and Neck Surgery: Bridging Tumor Biology to Perioperative Decision-Making, a...

To provide a comprehensive review of the biological rationale, clinical evidence, and practical perioperative management of immunotherapy for the head and neck surgeon.

Standard treatment for resectable head and neck squamous cell carcinoma (HNSCC) has reached a survival plateau, with over 50% of patients experiencing recurrence. The integration of immune checkpoint inhibitors (ICIs) into the neoadjuvant window represents a paradigm shift toward biologically adapted surgical intervention.

Neoadjuvant immunotherapy capitalizes on an intact immune substrate to create an in situ vaccine, avoiding the post-surgical immune desert that limits adjuvant efficacy. Emerging phase III data confirm that perioperative ICI significantly improves event-free survival. Successful implementation requires the surgeon to navigate unique diagnostic challenges, such as distinguishing rare but anatomically risky pseudoprogression from true progression. While combination therapies (chemoimmunotherapy or immunoradiotherapy) yield higher pathologic complete response rates, they also increase toxicity. Intraoperatively, ICI monotherapy generally preserves tissue planes without increasing surgical delays or major wound complications. Standard biomarkers like PD-L1 and TMB, alongside emerging tools such as liquid biopsy (ctDNA), are essential for patient selection and dynamic monitoring.

The transition to neoadjuvant immunotherapy facilitates future surgical de-escalation and function-preserving approaches. To optimize outcomes, the modern surgeon must act as a surgical immunologist, interpreting translational data to guide real-time operative planning.