In addition to the conventional aetiological risk factors for oropharyngeal squamous cell carcinoma (OPSCC), including tobacco use, alcohol consumption, and betel quid chewing, persistent infection with oncogenic human papillomavirus (HPV) has been established as an important causative factor in a subset of OPSCC cases. Patients with HPV-associated OPSCC have consistently been shown to exhibit improved survival outcomes compared with those with HPV-independent OPSCC, leading to the development of a distinct staging system for HPV-associated disease. Nevertheless, much of the current evidence regarding the prevalence, clinicopathological characteristics, and clinical outcomes of HPV-associated OPSCC has been derived predominantly from Caucasian populations. Consequently, the prevalence and clinical profile of HPV-associated OPSCC among Asian patients remain inadequately characterised. To address this knowledge gap, a cross-sectional multicentre study involving tissue analysis was conducted among Malaysian patients diagnosed with primary OPSCC over a five-year period from 1 January 2015 to 31 December 2019. HPV status was determined using p16INK4a immunohistochemistry performed on tissue microarrays constructed from archived formalin-fixed paraffin-embedded (FFPE) tissue specimens.