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There is evidence that the status of human papilloma virus subtype 16 (HPV-p16) alters the prognosis of patients with oropharyngeal squamous cell cancer (OSCC). We sought to establish whether there is a relationship between HPV-p16 status and 18F-FDG uptake in the prognosis of OSCC.Patients with newly diagnosed OSCC at our institution between June 2011 and June 2012 were retrospectively evaluated. All patients underwent a baseline 18F-FDG PET/computed tomographic scan and HPV-p16 testing. Tumour maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and total glycolytic activity (TGA) [defined as metabolic tumour volume (MTV) multiplied by SUVmean] were measured. All PET/computed tomographic scans were reviewed on a Siemens Syngo.via (version VA11B_HF03) workstation. A designated operator defined the region of the primary tumour with the MTV segmented by 40% of the SUVmax fixed threshold method.Seventy-nine patients aged 27–84 years met the criteria for inclusion in the study. The types of primary tumour were tonsillar squamous cell carcinoma in 48% and base of tongue squamous cell carcinoma in 29%. The mean SUVmax was 17.5 and 17.7 in HPV-p16-positive and HPV-p16-negative groups, respectively (P=0.90). The mean MTV was 8.36 and 7.07 ml in HPV-p16-positive and HPV-p16-negative patients, respectively (P=0.42). The mean TGA values were 96.3 and 82.5 g among the HPV-p16-positive and HPV-p16-negative patients (P=0.54). There was no significant difference between HPV-p16 status and tumour grading for any of the imaging markers.There were no statistically significant differences between HPV-p16-positive and HPV-p16-negative OSCC for any of the metabolic imaging markers (SUVmax, SUVmean, MTV and TGA) measured in this study.