Head and Neck Cancer

Importance: Head and neck cancer, which arises in the lining or mucosa of the upper aerodigestive tract, specifically the oral cavity, oropharynx, larynx, hypopharynx, and paranasal sinuses, is the seventh most common cancer worldwide. In 2024, approximately 71 110 individuals in the US were diagnosed with head and neck cancer, and it accounted for 16 110 deaths. Observations: Approximately 90% of head and neck cancers are squamous cell carcinomas. Worldwide, tobacco and alcohol use are the most prevalent risk factors. In the US and Europe, 60% to 70% of newly diagnosed oropharynx cancers (a subset of head and neck cancers) are caused by human papillomavirus (HPV) infection. At presentation, approximately 30% of patients with head and neck cancer have early-stage or localized disease (tumor <4 cm without regional lymph nodes involvement), 60% have locoregionally advanced disease (tumor ≥4 cm with local invasion and/or regional lymphadenopathy) and 10% have metastatic disease. Up to 10% of oropharynx squamous cell carcinomas present as squamous cell carcinomas of unknown primary. Standard treatment for localized head and neck cancer is surgery or radiotherapy, which are each associated with a 5-year overall survival rate of 70% to 90%. For locoregionally advanced head and neck cancer, multimodality treatment includes surgery followed by postoperative radiation with or without chemotherapy or concomitant chemotherapy (with cisplatin as the preferred agent), and radiation with surgery is reserved for persistent or recurrent disease. With these treatments for locoregionally advanced head and neck cancer, 5-year overall survival rates are 25% to 60% and more than 80% for HPV-associated oropharynx cancer. Choice of treatment for locoregionally advanced head and neck cancer should involve shared decision-making and consideration of effects on speech and swallow function and appearance. First-line treatment for patients with incurable locoregional recurrences or distant metastatic disease is immunotherapy with programmed death ligand-1 inhibition (ie, pembrolizumab) alone or in combination with platinum-doublet chemotherapy. With treatment, patients with incurable locoregional recurrences or distant metastatic disease have a median survival of 12 to 15 months, and 5-year survival rates are less than 20%. Conclusions and Relevance: Head and neck cancer is the seventh most common cancer worldwide. In the US and Europe, 60% to 70% of incident oropharynx cancers are associated with HPV infection. Standard treatment for localized head and neck cancer is surgery or radiotherapy. Locoregionally advanced disease is treated with surgery followed by radiation with or without chemotherapy or concurrent chemoradiation. First-line treatment for advanced disease is immunotherapy alone or with chemotherapy.