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HPV-attributable fraction in oropharyngeal cancer rose in seven countries over a decade

Central testing of 6,043 head and neck cancer specimens found HPV attributability in oropharyngeal cancer rose in all seven countries.

The BROADEN study measured HPV-attributable fractions in head and neck cancers in France, Germany, Italy, Portugal, Spain, China and Japan. Tissue from 6,043 patients at 88 hospitals was centrally tested for HPV-DNA, HPV-E6*I mRNA and p16INK4a. Oropharyngeal cancer required two of three positive tests; other sites required both DNA and mRNA positivity. In oropharyngeal cancer the fraction rose from 0% to 20.0% in Portugal and from 44.2% to 51.7% in Japan. Increases were significant in all countries except China and Japan; other sites stayed at 5% or less. The study is retrospective and uses hospital samples rather than population registries.

Why it is interesting: Gives like-for-like HPV attribution across seven countries using one central testing protocol. Shows the rise is confined to the oropharynx, with other head and neck sites flat.

Source
JNCI: Journal of the National Cancer Institute, 19 October 2026
Paper
Time trends of human papillomavirus-attributable head and neck cancers: the BROADEN study
Authors
Waterboer T, Zhao F, Giuliano A, Pavón MÀ, Qiao Y, Mirghani H et al.
DOI
10.1093/jnci/djag375
Type
Peer-reviewed article
Design
Retrospective multicentre tissue-based study, 6043 head and neck cancer patients, 88 hospitals, seven countries, two periods (2008-2009 and 2018-2019), central HPV-DNA, E6*I mRNA and p16 testing
Verdict
Refines prior evidence
Driver
Cancer
Driver
Revisions and new sources
Free full text
Free to read at the publisher
Abstract — the authors' own words, CC BY

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.

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