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Objective To analyse the association between high-risk human papillomavirus ( HR- HPV) and other risk factors in the aetiology of head and neck squamous cell carcinoma ( HNSCC) in an Asian population. Study Design This study is a cross-sectional analysis of 80 patients who were diagnosed with HNSCC. Patients' demographics, dietary habit, medical and social history were obtained. Surgical specimens from these patients were then histologically analysed using H&E stain and immunohistochemistry ( IHC) for the presence of HR- HPV primary antibody. Results High-risk human papillomavirus was detected in 41 patients, representing 51.3% of the 80 paraffin-embedded tissues of HNSCC; 27.5% of these were weak positive, 10.0% medium positive and 13.8% were strongly positive for the HR- HPV on IHC. The tongue lesions had the highest HR- HPV infection of 72.2%. No association existed between HR- HPV and patient's demographics, dietary habit and other predisposing factors. Conclusion The place of HR- HPV as a possible aetiological factor for HNSCC has further been established from this study. [ABSTRACT FROM AUTHOR]