Smoking impact on HPV driven head and neck cancer’s oncological outcomes?

•HPV-driven OPC have overall a good prognosis.•Smoking status at cancer diagnosis is the strongest prognostic factor for survival.•Half of HPV-positive patients have a smoking history and almost 35% smoked more than 20 PY.•Smoking cessation remains a priority in head and neck oncology even for HPV-positve patients. HPV-driven oropharyngeal cancer (OPC) patients have a better prognosis than their HPV-negative counterparts but several studies have suggested that among HPV-positive patients those with a smoking history had worse oncological outcomes. The aim of our study is to characterize the interplay between tobacco consumption, patient and disease characteristics, and disease control. All patients diagnosed with HPV-driven OPC and treated with curative intent between 2007 and 2009 and 2011–2016 at Gustave Roussy cancer center were included (n = 282). Demographic, clinical, morphological and tobacco consumption were correlated with oncologic outcomes. 157 (56%) patients had a positive smoking history, including 23.8% who were smoking at the time of diagnosis and 37.6% who had a tobacco consumption exceeding 20 pack-years. In multivariate analysis, the strongest prognostic factor for survival was smoking status at cancer diagnosis, with a hazard ratio (HR) for non-smokers compared to smokers of 0.25 ([0.12, 0.50], p = 0.0001). Smoking history, either more than 20 pack-years or smoking at diagnosis, was associated with local relapse and distant relapse. There was no difference in terms of comorbidity (p = 0.32) and radiotherapy duration (p = 0.93) according to tobacco consumption. Smoking is frequent among patients with HPV-driven OPC and increases the risk of death and oncologic failure.