Survival outcomes in head and neck squamous cell carcinoma of unknown primary: A national cohort study.

INTRODUCTION: To investigate factors influencing survival in head and neck squamous cell carcinoma of unknown primary (HNSCCUP). METHODS: A retrospective observational cohort study was conducted, over 5 years from January 2015, in UK Head and Neck centres, of consecutive adults undergoing 18F-Fluorodeoxyglucose-PET-CT within 3 months of diagnosis with metastatic cervical squamous cell carcinoma. Patients treated as HNSCCUP underwent survival analysis, stratified by neck dissection and/or radiotherapy to the ipsilateral neck, and by HPV status. RESULTS: Data were received from 57 centres for 965 patients, of whom 482 started treatment for HNSCCUP (65.7% HPV-positive, n = 282/429). Five-year overall survival (OS) for HPV-positive patients was 85.0% (95% CI 78.4-92.3) and 43.5% (95% CI 32.9-57.5) for HPV-negative. HPV-negative status was associated with worse OS, disease-free (DFS), and disease-specific (DSS) survival (all p < .0001 on log-rank test) but not local control (LC) (p = .16). Unilateral HPV-positive disease treated with surgery alone was associated with significantly worse DFS (p < .0001) and LC (p < .0001) compared to radiotherapy alone or combined modalities (5-year DFS: 24.9%, 82.3% and 94.3%; 5-year LC: 41.8%, 98.8% and 98.6%). OS was not significantly different (p = .16). Unilateral HPV-negative disease treated with surgery alone was associated with significantly worse LC (p = .017) (5-year LC: estimate unavailable, 93.3% and 96.6%, respectively). Small numbers with bilateral disease precluded meaningful sub-group analysis. CONCLUSIONS: HPV status is associated with variable management and outcomes in HNSCCUP. Unilateral neck disease is treated variably and associated with poorer outcomes when managed with surgery alone. The impact of diagnostic oropharyngeal surgery on primary site emergence, survival and functional outcomes is unestablished.