How Can We Address the Challenge of Distant Metastases in HNSCC Prognosis?

Head and neck squamous cell carcinoma (HNSCC) is the eighth most common cancer worldwide. Distant metastasis is the cause of treatment failure in up to 15 - 30% of HNSCC patients; prognosis is generally dismal with a median overall survival of 6-8 months. Three main strategies can be implemented to address this serious clinical issue. First, risk factors have to be managed with strategies aimed to quit smoking and alcohol consumption as well as to improve the worldwide HPV vaccination coverage. Second, increasing the treatment intensity; new therapeutic strategies, including immunotherapy and proton therapy combined with multi-omics data, i.e. artificial intelligence and radiomics, will be helpful to improve high-risk patients' selection. Lastly, early detection of the minimal residual disease with circulating ctDNA and management of oligometastatic patients, could contribute in the burden reduction of distant metastases.