The changing therapeutic landscape of head and neck cancer

Head and neck cancers are a heterogeneous collection of malignancies of the upper aerodigestive tract, salivary glands and thyroid. In this Review, we primarily focus on the changing therapeutic landscape of head and neck squamous cell carcinomas (HNSCCs) that can arise in the oral cavity, oropharynx, hypopharynx and larynx. We highlight developments in surgical and non-surgical therapies (mainly involving the combination of radiotherapy and chemotherapy), outlining how these treatments are being used in the current era of widespread testing for the presence of human papillomavirus infection in patients with HNSCC. Finally, we describe the clinical trials that led to the approval of the first immunotherapeutic agents for HNSCC, and discuss the development of strategies to decrease the toxicity of different treatment modalities. The authors of this Review discuss treatments currently available for patients with head and neck squamous cell carcinomas (focusing in those of the oral cavity, oropharynx, hypopharynx and larynx). Advances in surgical and non-surgical approaches (mainly combinations of radiotherapy and chemotherapy) are discussed, including the first immunotherapeutic agents approved for these malignancies. Key points Current treatments for human papillomavirus-driven (HPV + ) oropharyngeal squamous cell carcinoma (OPSCC), primarily derived from those for the more aggressive HPV − head and neck squamous cell carcinoma (HSNCC), might be more intensive than necessary for patients with favourable risk features and an excellent prognosis. Multiple prospective studies have investigated various treatment de-intensification strategies with promising early results; however, pending definitive conclusions, HPV + OPSCC should continue to be treated with established standard-of-care therapies, known to yield very high survival. Minimally invasive transoral surgical techniques provide an alternative treatment option for OPSCC; retrospective evidence is promising, but results from prospective randomized trials are required to fully integrate these approaches into the treatment armamentarium. More-precisely targeted radiotherapy (with incorporation of intensity-modulated radiation therapy, molecular imaging-guided therapy, adaptive therapy and proton beam therapy) has the potential to decrease the long-term toxicity of radiotherapy. Anti-EGFR therapy with cetuximab improves survival in the curative and recurrent and/or metastatic settings; however, no other mol