Changing epidemiology and survival of HPV-associated oropharyngeal cancer in Denmark: four decades of population-based data

Abstract

Background Oropharyngeal squamous cell carcinoma (OPSCC) has undergone substantial epidemiological and clinical changes, with an increasing proportion of human papillomavirus (HPV)-associated tumours and declining tobacco exposure. We investigated temporal changes in patient characteristics, HPV/p16 status, treatment patterns, and survival among patients with OPSCC in Denmark. Methods Patients with OPSCC were identified from the Copenhagen Oropharyngeal Cancer Database (2000–2023) and the Danish National Patient Cancer Registry (DCR; 1980–2021). The Copenhagen database provided detailed clinical and pathological data, including HPV/p16 status, while the DCR enabled assessment of long-term survival trends. Temporal changes were evaluated across diagnostic periods. Overall survival, relative survival, and restricted mean survival time were estimated. Results Among 3,631 OPSCC patients in the Copenhagen database, median age at diagnosis increased from 59 years in 2000–2005 to 64 years in 2018–2023 (p<0.001). The proportion of HPV+/p16+ patients increased significantly from 43.5% in 2000–2005 to 62.8% in 2018-2023. The proportion of never smokers also increased from 0.5% to 23.5%, while ≥20 pack-years decreased from 73.2% to 52.1% (p<0.001). Treatment patterns changed substantially, with radiotherapy alone decreasing from 87.6% to 27.9% and chemoradiotherapy increasing from 1.6% to 46.3%. Among 9,379 patients in the DCR, five-year relative survival increased from 31.8% in 1980–1984 to 70.1% in 2015-2019. Among HPV+/p16+ patients, five-year overall survival increased from 63.1% in 2000–2005 to 83.7% in 2018–2023. Conclusion In Denmark, OPSCC has undergone substantial epidemiological and therapeutic changes accompanied by marked improvements in survival, including among HPV+/p16+ patients.