Background: Smoking, alcohol consumption, and human papillomavirus (HPV) infection are known risk factors for oral cancer. Researchers have examined each of these risk factors independently, but few have observed the potential risk of their interaction. In this study, we investigated the interactions among smoking, alcohol consumption, and HPV exposure and their effect on risk of oral cancer.
Methods: Totally 377 patients with newly diagnosed oral cancer and 433 cancer-free controls who were frequency-matched by age and sex were included. Multivariable logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
Results: Consistent with historical evidence, we found that oral cancer risk was independently associated with smoking (adjusted OR(aOR): 1.3, 95% CI: 1.0-1.9), alcohol consumption (aOR: 1.4, 95% CI: 1.1-2.0), and HPV16 seropositivity (aOR: 3.3, 95% CI: 2.2-4.8), respectively. Additionally, we found that HPV16 seropositivity increased the risk of oral cancer in ever-smokers (aOR: 6.4, 95% CI: 3.3-12.7) and ever-drinkers (OR: 4.4, 95% CI: 2.6-7.3), while HPV16-seronegative ever-smokers and ever-drinkers had less than a twofold increase in risk of oral cancer (aORs: 1.1, 95% CI: 0.8-1.7 and 1.6, 95% CI: 1.1-2.4, respectively). Furthermore, the increased risk was particularly high for oropharyngeal cancer in HPV16-seropositive ever-smokers (aOR: 12.3, 95% CI: 5.7-26.3) and in HPV16-seropositive ever-drinkers (aOR: 9.8, 95% CI: 5.3-18.3).
Conclusion: These results suggest a strong combined effect of HPV16 exposure, smoking, and alcohol on oral cancer, which may indicate a strong interaction between HPV16 infection and smoking and alcohol consumption, particularly for oropharyngeal cancer.