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The eighth edition of the TNM classifies oropharyngeal squamous cell carcinomas (OSCCs) depending on p16 status. Some imaging features are reportedly associated more frequently with p16-positive (P16+) OSCC than p16-negative (p16−) OSCC. However, classical risk factors such as tobacco use were not specifically considered when assessing these imaging features. We aimed to evaluate whether P16+ OSCCs have different epidemiological, clinical, prognostic and imaging features depending on smoking status, and to compare P16+ and p16− groups. A retrospective study of data from 85 patients with P16+ OSCC (41 non-smokers, 44 smokers) and 36 with p16− OSCC from 2011 to 2020 was carried out, assessing epidemiological data, clinical aspects of the tumour and presence of adenopathy. Staging was assessed according to the seventh and eighth editions of the TNM. Compared with P16+ OSCC non-smokers, P16+ OSCC smokers had tumours that were less well-defined (36.6% vs 77.8%, p < 0.001), more ulcerated (85.4% vs 44.4%, p < 0.001) and more necrotic (53.7% vs 25%, p = 0.012). There was also less downstaging from N2 or N3 of the seventh edition of the TNM to N1 of the eighth edition for smokers than non-smokers (22.7% vs 43.9%, p = 0.042). Compared with p16− tumours, more P16+ tumours had well-defined contours (55.8% vs 22.2%, p = 0.001), were exophytic (89.6% vs 72.2%, p = 0.023), less necrotic (40.3% vs 80.6%, p < 0.001), less ulcerated (97.2% vs 66.2%, p = 0.006) and involved less muscle tissue (26.0% vs 47.2%, p = 0.027).P16+ OSCCs of smokers show clinical, imaging and prognostic differences with P16+ OSCCs of non-smokers.

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