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

• Published in: Cancer science Vol. 115; no. 8; pp. 2808 - 2818
• Main Authors: Nibu, Ken‐ichi, Oridate, Nobuhiko, Saito, Yuki, Roset, Montserrat, Forés Maresma, Marta, Cuadras, Daniel, Morais, Edith, Roberts, Craig, Chen, Ya‐Ting, Spitzer, Jacque, Sato, Kayo, Saito, Itori, Tazaki, Ichiro, Clavero, Omar, Schroeder, Lea, Alemany, Laia, Mehanna, Hisham, Mirghani, Haitham, Giuliano, Anna R., Pavón, Miquel Angel, Waterboer, Tim
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.08.2024
• Subjects: Alcohol; Data collection; Deoxyribonucleic acid; DNA; Epidemiology; Genotypes; Head & neck cancer; Head and neck; HPV attributability; HPV genotype; HPV‐driven HNC; HPV‐driven vaccine; Human papillomavirus; Immunohistochemistry; INK4a protein; Laboratories; Larynx; mRNA; Oncology; Oral cavity; Oropharyngeal cancer; Oropharynx; p16 Protein; Patients; Polymerase chain reaction; Women; Japan; HPV attributability; oropharyngeal cancer; HPV‐driven HNC; HPV genotype; HPV‐driven vaccine
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/cas.16230

There is limited understanding of epidemiology and time trends of human papilloma virus (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 mRNA positivity for non‐oropharynx sites. Nineteen hospitals included a total of 1108 patients, of whom 981 had valid samples. Men accounted for 82% of HNC diagnoses. Patients in the earlier cohort were younger and included a higher percentage of smokers. There was an increasing trend of HPV‐driven oropharyngeal cancer over the last decade, from 44.2% to 51.7%. HPV attribution in nasopharyngeal cancers was 3.2% in 2008–2009 and 7.5% in 2018–2019; and 4.4% and 0% for larynx respectively. In total, 95.2% of HPV‐driven HNC were attributed to HPV genotypes included in the 9‐valent HPV vaccine being HPV16 the most prominent genotype. These results suggest that an epidemiologic shift is happening in Japan, with a decrease in smoking and alcohol use and an increase in HPV‐driven HNC. The increasing trend of HPV‐driven HNC in Japan highlights the need for preventive strategies to mitigate the rise of HPV‐driven HNC. The BROADEN study is one of the largest observational studies conducted in Japan assessing human papilloma virus (HPV) in head and neck cancer (HNC). The study includes 1108 patients diagnosed in 2008–2009 and 2018–2019 across 19 hospitals. Overall 981 HNC samples were tested by HPV‐DNA PCR, p16INK4a, and HPV E6*I mRNA in a central laboratory using strict quality control processes for all laboratory steps. This study demonstrates an increasing trend of HPV attributability in oropharyngeal cancer over this 10‐year period, from 44.2% in 2008–2009 to 51.7% in 2018–2019 reflecting an annual percentage change (APC) of 1.58%, as well as in nasopharyngeal cancers from 3.2% to 7.5% representing an APC of 8.92%. Men accounted for 82% of HNC diagnoses, and patients in the earlier cohort were younger and had a higher percentage of smokers. Notably, the study found that 94.6% of these HPV‐driven HNC cases were attributed to HPV genotypes included in the prophylactic 9‐valent HPV vaccine highlighting the value of potential preventive strategies.