Perioperative immunotherapy in head and neck squamous cell carcinoma

Abstract

Outcomes for patients with resectable head and neck squamous cell carcinoma (HNSCC) remain suboptimal despite multimodal therapy, with high rates of recurrence and patients suffering from toxicity of treatments. Immune checkpoint inhibitors, which have transformed the management of recurrent and metastatic disease, have been advanced into the perioperative and adjuvant settings. Recent phase III trials mark a turning point: the addition of adjuvant nivolumab improved disease-free survival in pathologic high-risk resected HNSCCs, while perioperative pembrolizumab significantly prolonged event-free survival in resectable locally advanced HNSCCs, supporting a shift toward integrated perioperative immunotherapy strategies. Although the former approach fits into a conventional adjuvant framework, biological insights suggest that neoadjuvant delivery enables effective immune priming extending therapeutic approaches. Together, these advances redefine therapeutic strategies in resectable HNSCC and highlight the potential of perioperative immunotherapy to improve long-term outcomes.