Prognostic significance of distant metastasis site at diagnosis in HPV-related oropharyngeal cancer.

INTRODUCTION: This study aimed to determine whether different distant metastasis (DM) sites at the time of diagnosis exhibit distinct survival outcomes human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC), and to assess whether intensifying treatment with local surgery or radiotherapy (RT) offers particular advantages for specific subcategories of patients. METHODS: A retrospective cohort study included patients with invasive OPSCC with single-site DM at diagnosis between 2010 and 2020 from the US National Cancer Database (NCDB). Hazard ratios (HR) for overall survival were estimated with the corresponding 95% confidence interval (95% CI). RESULTS: A total of 780 patients were included. Patients with distant lymph node demonstrated better survival compared to lung (adjusted HR: 1.45; 95 % CI: 1.10 - 1.93; p = 0.009), liver (adjusted HR: 1.97; 95 % CI: 1.35 - 2.88; p < 0.001), and bone (adjusted HR: 1.90; 95 % CI: 1.39 - 2.59; p < 0.001) metastases. Locoregional RT showed survival benefit compared to no treatment (adjusted HR: 0.71; 95 % CI: 0.57 - 0.88; p = 0.002), particularly for patients with distant lymph node (adjusted HR: 0.64; 95 % CI: 0.41 - 1.00; p = 0.05) and lung (adjusted HR: 0.72; 95 % CI: 0.51 - 1.00; p = 0.05) metastases. CONCLUSIONS: Patients diagnosed with isolated distant lymph node metastases in HPV-positive OPSCC demonstrate a more favorable prognosis compared to those with metastases at other sites. Our results suggest that RT may confer a survival advantage for patients with distant lymph node and lung metastases, potentially enhancing their long-term outcomes.