Multicentre study of inoperable HPV-negative head and neck cancer: a persistent real-world challenge.

BACKGROUND: HPV-negative head and neck squamous cell carcinoma (HNSCC) has a poorer prognosis than HPV-positive tumours, yet real-world outcomes remain understudied. This study analyses a multicentre cohort of HPV-negative HNSCC patients, including those over 65 years of age. MATERIALS AND METHODS: This retrospective study included HPV-negative HNSCC patients treated with definitive radiotherapy (RT) or chemoradiotherapy (CRT) between 2015 and 2020. RT protocols included standard fractionation (70 Gy, 35 fractions), simultaneous integrated boost (69.96 Gy, 33 fractions), or concomitant boost (72.5 Gy, 50 fractions). RESULTS: Among 225 patients (62 over 65 years), 138 (61%) received CRT. Local progression occurred in 83 (37%), and 177 (79%) died. Median overall survival (OS) was 23.1 months, with 3-year OS and local control (LC) rates of 37% and 35%, respectively. ECOG predicted outcomes (p < 0.001 for OS, p = 0.040 for LC), while comorbidity burden and disease stage were significant only for OS (p < 0.001 and p = 0.006). CRT improved OS over RT alone (p = 0.059). Older patients more often had hypopharyngeal/laryngeal tumours (p = 0.033), received CRT less frequently (29% vs. 74%, p < 0.001), and chemotherapy did not affect outcomes. CONCLUSIONS: Real-world outcomes for inoperable HPV-negative HNSCC remain poor. Personalized approaches are needed to improve care for this challenging population.