Head and neck cancer of unknown primary: a nationwide analysis of hospital-based cancer registry data in Japan, 2018-2022.

Abstract

Background: Some head and neck cancers are metastatic tumors of unknown primary origin, but their epidemiology has seldom been studied. This study aimed to address this knowledge gap using a nationwide database in Japan. Furthermore, we examined the nationwide implementation of human papillomavirus (HPV) and Epstein-Barr virus (EBV) testing, assessed their inter-facility and temporal variations, and compared these findings with oropharyngeal cancer cases.

Methods: Head and neck squamous cell carcinoma of unknown primary origin and oropharyngeal squamous cell carcinoma diagnosed between 2018 and 2022 were identified from the Hospital-based Cancer Registries of Japan. Data on sex, age, TNM classification, HPV and EBV test results, and treatment facilities were collected. Temporal changes in viral diagnostic practices were analyzed.

Results: We identified 1636 new cases of head and neck cancers of unknown primary. The disease was more common in males and patients aged 70-74 years. HPV positivity was more frequent in patients aged 45-59 years, whereas EBV positivity was less frequent in all age groups. Of the patients, 67.6% were treated at certified head and neck cancer facilities, which had higher viral testing rates than non-certified facilities. Case numbers remained stable over time, whereas viral testing and HPV positivity increased; however, both remained lower than in oropharyngeal cancer cases.

Conclusions: This study visualized real-world virus testing for patients with head and neck cancers of unknown primary, providing insights into diagnostic equity, institutional capacity, and the need for standardized cancer care. Continued surveillance is essential to improve outcomes in this rare condition.