Time trends of human papillomavirus-attributable head and neck cancers: the BROADEN study

BACKGROUND: The incidence of human papillomavirus (HPV)-driven oropharyngeal cancer (OPC) is increasing in several Western countries, but this trend is less well understood in other geographical regions and for other head and neck cancers (HNC). The BROADEN (absolute BuRden Of HPV relAteD hEad and Neck) study assessed HPV-attributable fractions (HPV-AFs) of HNC including OPC in France, Germany, Italy, Portugal, Spain, China, and Japan over a 10-year period. METHODS: This retrospective study included patients diagnosed with HNC (oropharynx, oral cavity, nasopharynx, hypopharynx, and larynx cancer) in two time periods, 2008-2009 and 2018-2019. Formalin-fixed tissue samples were centrally tested for HPV-DNA, HPV-E6*I mRNA, and p16INK4a immunohistochemistry. HPV attributability required positive results in two of the three tests for OPC, and both HPV-DNA and HPV-E6*I mRNA positivity for other HNC. RESULTS: Among 6043 patients from 88 hospitals, the HPV-AF in OPC shown an increasing trend across all countries, with an HPV-AF ranging between 0% in Portugal and 44.2% in Japan in 2008-2009, and 20.0% and 51.7%, respectively, in 2018-2019. The increasing trend reached the statistical significance at 0.05 in all countries except China and Japan. Japan had the highest HPV-AF in 2008-2009. Other HNC showed lower HPV-AF (≤5%) with no time trends. CONCLUSION: BROADEN is the first and largest study to date to investigate HPV causality and its time trends across five HNCs in seven countries. These results support the understanding of time trends and geographic variation in HPV-AF and are essential for global HNC prevention and treatment.