Metastatic patterns, outcomes, and prognostic factors in de novo metastatic head and neck cancer by tumor HPV status.

Abstract

To describe metastatic characteristics and outcomes in patients with de novo metastatic (cM1) head and neck squamous cell carcinoma (HNSCC). cM1 HNSCC patients diagnosed between 2001 and 2024 were reviewed. Metastatic characteristics and management patterns were collected, including the timing of locoregional radiotherapy (LR-RT) relative to first-line systemic therapy. Overall survival (OS) was estimated using the Kaplan-Meier method, and multivariable Cox regression analyses (MVA) identified prognostic factors. Among 10,273 newly diagnosed HNSCC cases, 222 (2.2%) had cM1 disease (HPV-associated: 48/2593 [1.9%]; HPV-independent: 174/7680 [2.3%]). cM1 characteristics were similar between HPV-associated and HPV-independent disease, including oligometastatic presentation (1-5 lesions; 31% vs 43%, p = 0.21) and frequency of lung-only metastases (83% vs 77%, p = 0.46), although mediastinal involvement was more common in HPV-associated disease (40% vs 23%, p = 0.034). LR-RT was delivered to 191 (86%) patients: 127 (57%) as sole treatment, 55 (25%) before, and 9 (4%) after first-line systemic therapy. After median follow-up of 25 months, median OS was 7 months (6.0-8.8). On MVA, LR-RT (HR 0.49 [0.32-0.75]), HPV-associated disease (HR 0.62 [0.43-0.88]), ECOG 0-1 (HR 0.63 [0.47-0.86]), first-line immunotherapy (HR 0.52 [0.33-0.82]), and lung-only metastases (HR 0.67 [0.48-0.95]) were associated with longer OS. Among patients receiving LR-RT, a radiation dose ≥ 50 Gy was associated with improved OS (HR 0.53 [0.34-0.83]). cM1 HNSCC has a poor prognosis, highlighting a substantial unmet need. First-line immunotherapy and LR-RT, particularly with ≥ 50 Gy, were associated with improved OS and warrant prospective evaluation.