, respectively), with outcomes significantly worsening with increasing smoking exposure. The 5-year OS for more than 10, 20, and 30 pack-year smoking history was 73.2%, 64.7%, and 59.1% respectively. Current smokers managed with CRT had a 5-year OS of 64.2% compared with former and never smokers (93.1% and 78.2%, respectively). For current smokers managed primarily by surgery, the 5-year OS was 57.6% compared with former and never smokers (69.6% and 73.5%, respectively). Conclusion: Smoking is an independent prognostic factor in HPVassociated locally advanced OPC. Current smokers and those with higher smoking exposure had poorer outcomes irrespective of their primary modality of treatment, and therefore it is not possible to recommend a preferential modality of treatment for patients with HPV positive tumors who have a significant smoking history. Outcomes were worse for patients managed surgically compared to CRT; however, as this review did not specifically compare outcomes between the two treatment modalities, this requires further evaluation.