Novel Immunotherapeutic Approaches for Patients with Head and Neck Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (CSCC) is the second most common type of skin cancer and typically involves the head and neck. Systemic therapy is often required for patients with advanced CSCC to achieve optimal disease control. Immune checkpoint inhibitors (ICIs) are now the standard of care for these patients, with a 50%–60% response rate and sustainable remission for at least 30% of patients. Given the activity of ICIs in advanced head and neck CSCC, ICIs are being studied in early-stage disease or neoadjuvant situations. The purpose of this review is to provide an overview of the innovative perioperative strategies in resectable disease and discuss novel immunotherapeutic strategies designed to overcome treatment resistance. In conclusion, neoadjuvant ICIs have demonstrated impressive response rates with unclear survival benefit. The effectiveness of adjuvant ICIs is currently being explored. Emerging biomarkers, such as circulating tumor DNA (ctDNA), will be crucial for optimizing patient selection and improving treatment outcomes.