Recent highlights and breakthroughs in immunotherapy for head and neck cancers

PURPOSE OF REVIEW: This review highlights recent advances in immunotherapy for head and neck oncology, focusing on pivotal studies, both early-stage and late-stage, published or presented in 2025. RECENT FINDINGS: Noteworthy results were reported with immune checkpoint inhibitors in mucosal squamous cell carcinoma of the head and neck (SCCHN) (KEYNOTE-689 and NIVOPOSTOP trials evaluating pembrolizumab and nivolumab, respectively, in the perioperative setting); in nasopharyngeal carcinoma (DIPPER and DIAMOND trials evaluating camrelizumab and toripalimab, respectively, in the curative setting with radiotherapy, and tagitanlimab in recurrent and/or metastatic disease); in cutaneous squamous cell carcinoma of the head and neck region (C-POST trial in the adjuvant setting and the combination of avelumab with cetuximab in the palliative setting); and in BRAF V600E-mutated anaplastic thyroid carcinoma (pembrolizumab with dabrafenib and trametinib). Passive immunotherapy targeting tumor-associated antigens also showed encouraging activity in R/M-SCCHN (petosemtamab, ficerafusp-alfa, amivantamab, enfortumab vedotin) and in heavily pretreated R/M nasopharyngeal carcinoma (antibody-drug conjugates becotatug vedotin and izalontamab brengitecan [iza-bren]). SUMMARY: Recent advances highlight a rapid surge in positive immunotherapy trials across different head and neck cancer entities, with clinical benefit observed both when immune checkpoint inhibitors are moved earlier in the disease course and when they are combined with agents targeting resistance mechanisms or enabling more precise drug delivery to tumors.