Human papillomavirus-driven head and neck cancers in Japan during 2008–2009 and 2018–2019 - The BROADEN study

Sep 21, 2026

Uploaded by Oliver

Limited understanding of epidemiology and time trends of human papillomavirus (HPV)-driven head and neck cancers in Japan—especially outside the oropharynx—motivates the BROADEN non-interventional study. Patients diagnosed in 2008–2009 and 2018–2019 were evaluated across oropharyngeal, nasopharyngeal, laryngeal, hypopharyngeal, and oral cavity sites. HPV was centrally tested with p16INK4a immunohistochemistry, HPV-DNA PCR, and HPV E6*I mRNA, using multi-test positivity for attribution. Results report increasing HPV-driven oropharyngeal cancer, subtype attribution linked to vaccine genotypes, and an epidemiologic shift alongside changing smoking and alcohol patterns.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages11

Reading Time28 min

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Abstract

Study design and HPV testing

Patient cohorts and key results

Introduction

Burden and incidence of head and neck cancer

Risk factors and emerging HPV trends

Received: 7 November 2023 | Revised: 18 April 2024 | Accepted: 11 May 2024 | DOI: 10. 1111/cas.16230 | | | --- | --- | | OR I G I NAL ART I C L E
| | | Human papillomavirus-driven head and neck cancers in Japan during 2008–2009 and 2018–2019: The BROADEN study
Ken-ichi Nibu1 | Nobuhiko Oridate2 | Yuki Saito3 | Montserrat Roset4 | Marta Forés Maresma4 | Daniel Cuadras4 | Edith Morais5 | Craig Roberts6 | Ya-Ting Chen6 | Jacque Spitzer6 | Kayo Sato7 | Itori Saito7 | Ichiro Tazaki7 | Omar Clavero8,9 | Lea Schroeder10 | Laia Alemany8,9 | Hisham Mehanna11 |
Haitham Mirghani12 | Anna R. Giuliano13 | Miquel Angel Pavón8,9 | Tim Waterboer10
1Department of Otolaryngology-Head and Neck Surgery, Kobe University, Graduate School of Medicine, Kobe, Hyogo, Japan 2Department of Otolaryngology, Head and Neck Surgery, School of Medicine, Yokohama City University, Yokohama, Kanagawa, Japan 3 Department of Otolaryngology, Head and Neck Surgery, University of Tokyo, Tokyo, Japan
4IQVIA, Barcelona, Spain
5MSD France, Puteaux, France
6Merck & Co. , Inc. , Rahway, New Jersey, USA 7MSD K. K. , Tokyo, Japan
8Cancer Epidemiology Research Program, Catalan Institute of Oncology, IDIBELL, EPIBELL, Barcelona, Spain
9Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain 10German Cancer Research Center (DKFZ), Heidelberg, Germany
11Institute of Head & Neck Studies and Education (InHANSE), University of Birmingham, Birmingham, UK
12Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Hôpital Européen Georges Pompidou, APHP, Université Paris-Cité, Paris, France 13Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA | | | Correspondence
Tim Waterboer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Email: t.waterboer@dkfz-heidelberg.de
Funding information
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. , Inc. , Rahway, NJ, USA. |
Abstract
There is limited understanding of epidemiology and time trends of human papillomavirus (HPV)-driven head and neck cancers (HNC) in Japan, especially outside of the oropharynx. To assess HPV-driven HNC, a non-interventional study (BROADEN) of HNC patients diagnosed in 2008–2009 and 2018–2019 was conducted in Japan. Adult patients with oropharyngeal, nasopharyngeal, laryngeal, hypopharyngeal or oral cavity cancers were included in this study. HPV was centrally tested using p16INK4a immunohistochemistry, HPV-DNA PCR and HPV E6*I mRNA. HPV attributability required positivity in at least two tests (p16INK4a immunohistochemistry, HPV-DNA PCR, HPV E6*I mRNA) in the oropharynx, and HPV-DNA and HPV E6*I | | Abbreviations: AF, attributable fraction; AJCC, American joint committee on cancer; APC, annual percentage change; BML, biomedical laboratory; DEIA, DNA enzyme immunoassay; DKFZ, Deutsches Krebsforschungszentrum; EBV, Epstein–Barr virus; ERC, ethics review committee; FFPE, formalin-fixed paraffin-embedded; HNC, head and neck cancer; HPV, human papilloma virus; ICO, Institute of Oncology; IHC, immunohistochemistry; IRB, institutional review board; LIPA, line probe assay; NCR, national cancer registry; OPC, oropharyngeal cancer; OR, odds ratio; SCC, squamous cell carcinoma; SPF, short-fragment.
Miquel Angel Pavón and Tim Waterboer contributed equally to this work. | | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2024 Merck Sharp and Dohme LLC and The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. NIBU et al. 2809 mRNA positivity for non-oropharynx sites. Nineteen ho

FAQs

What is the main purpose of the BROADEN study in Japan?

The study evaluates epidemiology and time trends of HPV-driven head and neck cancers in Japan, with particular attention to disease sites outside the oropharynx.

Which HPV assays were used to test HPV status in tumors?

HPV was centrally tested using p16INK4a immunohistochemistry, HPV-DNA PCR, and HPV E6*I mRNA, with attribution requiring positivity in at least two tests in the oropharynx.

What trends were observed for HPV-driven oropharyngeal and other head and neck cancers?

HPV-driven oropharyngeal cancer increased over the last decade, while HPV attribution in nasopharyngeal cancers rose, and laryngeal cancers showed very low or no HPV attribution in the later cohort.

Sep 21, 2026

Uploaded by Oliver