Background Persistent human papillomavirus (HPV) infection is an important risk factor for a subset of head and neck cancers (HNCs). However, estimates of the HPV-attributable fraction of oropharyngeal cancers vary greatly, and the proportion is increasing. Growing evidence indicates smaller proportions of oral cavity and laryngeal cancers are also HPV-attributable, but this requires further investigation. The primary objective of the BROADEN study is to estimate the fraction of HNCs attributable to HPV in selected European and Asian countries by anatomic site. Secondary objectives are to determine HPV genotypes involved and to describe primary tumor and patient characteristics by HPV status. Methods BROADEN is a non-interventional, cross-sectional study of patients with HNC in China, France, Germany, Italy, Japan, Portugal, and Spain. The HPV-attributable HNC fraction will be determined within pre-defined time-periods (2008–2009, 2013–2014 [China only], 2018–2019). Approximately 9000 patients from an estimated 90 hospitals with reference HNC diagnostic units and local reference pathology laboratories will participate. Sample size estimates were generated by grouped anatomic site (oropharynx, oral cavity, nasopharynx, hypopharynx, and larynx) and country. HPV testing (HPV-DNA and p16 immunohistochemistry [IHC]) will be performed at a central laboratory on formalin-fixed paraffin-embedded tissue samples. All HPV-DNA-positive samples and HPV-DNA-negative/p16 IHC-positive samples, plus 10% of remaining HPV DNA-negative (control) samples will be tested for HPV mRNA. Discussion BROADEN is a large global epidemiologic study to estimate current and recent past HPV burden in oropharyngeal and non-oropharyngeal HNCs. BROADEN is expected to provide robust estimates of HPV attributability by anatomic site in participating countries.