Top advances of the year: Head and neck cancer.

Advances in treatment deintensification for human papillomavirus-associated oropharyngeal cancer include use of transoral surgery to permit reduction in pathologic risk-based postoperative therapy after transoral resection. The E3311 cooperative group trial demonstrated 3-year progression-free survival (PFS) of 95% for intermediate risk patients treated with 50 Gy radiation alone, with no decrement for those with a smoking history. Favorable risk patients could be observed, with a 3-year PFS of 93%. Reduction in radiation dose is also feasible for favorable risk patients (low or no smoking history and low stage) treated with chemoradiation on the NRG HN002 trial, where 2-year PFS was 90.7%. For those favorable risk patients treated with radiation alone, 2-year PFS was 87.7% and this arm did not meet criteria for further testing. Important phase 3 trials of immunotherapy in first-line treatment of recurrent and/or metastatic head and neck cancer were also reported in 2022. For patients with nonnasopharyngeal sites of disease, the combination of the programmed death-1-directed antibody nivolumab plus the anti-CTLA-4 agent ipilimumab was not superior to chemotherapy plus cetuximab in the Checkmate 651 trial. However, in an important breakthrough for patients with nasopharyngeal cancer, the JUPITER-02 trial, conducted in China, Singapore, and Taiwan among patients with predominantly Epstein-Barr virus-related cancers, demonstrated a significant improvement in PFS (hazard ratio, 0.52) when toripalimab was added to gemcitabine/cisplatin chemotherapy. Immature survival data indicate overall survival will likely also be impacted.