Incidence and outcome of oropharynx carcinoma in Denmark 1986–2020: A population based DAHANCA study

Purpose The global incidence of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) varies widely. Long-term, population-based studies with consistent treatment protocols are essential for understanding geographic differences in viral impact, treatment response and survival. With this nationwide population-based study, we aimed to examine gender- and age-specific incidence and survival trends in Danish patients with OPSCC from 1986 to 2020, in relation to HPV-status and treatment intensification. Methods All Danish patients diagnosed with OPSCC were prospectively collected via the Danish Head and Neck Cancer Group (DAHANCA) database and national health registries. Patients were treated according to prevailing national clinical guidelines. Age-standardized, gender-specific incidence rates were calculated. Five-year disease-free (DFS) and overall survival (OS) were estimated using Cox proportional hazards models with HPV-related p16 expression and radiotherapy-based treatment intensification as exposures. Confounding and indirect effects were assessed using a counterfactual framework adjusted for calendar period, age, stage, smoking and gender. Results A total of 8499 patients were identified, with a 2.8:1 male:female ratio. Overall crude incidence increased from 1.4 to 7.7 (men:2.1–11.5, women:0.8–3.9) in parallel with an increasement in HPV-relation from 30% to 69%. Five-year OS improved by 35% in the total cohort (from 31% to 66%), and treatment intensification resulted in improved adjusted 5-year OS by 29% (HR 0.22, 95% CI, 0.15–0.33), irrespective of HPV-status. Conclusions Denmark is a high-incidence area for HPV-related OPSCC. Improved survival over the 35-year period is largely attributable to nationally implemented intensified treatment strategies, with benefits observed regardless of HPV-status.