Abstract
Rare tumor entities in the head and neck region are biologically heterogeneous, frequently only investigated in small cohorts, and therapeutically challenging. The current article critically contextualizes clinically relevant studies presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting on salivary gland, thyroid, and nasopharyngeal cancer and cutaneous squamous cell carcinoma. In adenoid cystic carcinoma, several molecularly targeted strategies have shown early activity, including MYB degradation, NOTCH inhibition, and a B7-H4-directed antibody-drug conjugate. In other salivary gland cancers, HER2-directed therapy and androgen receptor blockade were relevant. In thyroid cancer, selective tyrosine kinase inhibition and multimodal concepts for anaplastic carcinoma confirmed the importance of molecular diagnostics and repeated assessment of operability. In nasopharyngeal cancer, cadonilimab in combination with chemotherapy prolonged progression-free survival after failure of immunotherapy. In cutaneous squamous cell carcinoma, definitive irradiation with cemiplimab and adjuvant immunotherapy were investigated. Overall, the data support biomarker-based and interdisciplinary treatment pathways; however, given the small, often single-arm studies, the data should be interpreted with caution.