Objective:
Human papillomavirus (HPV) infection is a major risk factor for cervical cancer and may also be related to development of oral cancer. The objective of this study was to provide updated information regarding association between oral HPV prevalence and smoking in people without oral cancer.

Methods:
We systematically reviewed 29 studies which reported the prevalence of oral HPV infection that included 22,756 subjects (age range 2-89 years) and were published from January 2012 to June 2015. Additionally, we investigated oral HPV16 prevalence by PCR using type specific primer in 256 patients who visited Hiroshima University Hospital from 2014 to 2018. The study design was approved by the Ethical Committee of Hiroshima University.

Results:
The prevalence of overall HPV was considerably higher in males who had sex with males (12.2%) as compared to heterosexual men (4.7%) and women (2.9%). A meta-analysis revealed a significant statistical association of sexual behavior and smoking with oral HPV infection (OR = 1.90, 95% CI = 1.51-2.39, P <0.0001; OR = 2.13, 95% CI = 1.32-3.43, P = 0.002, respectively). Men showed a significantly higher rate of HPV16 than females (P=0.021). In addition, female smokers showed an increased percentage of HPV16 infection as compared with male smokers, but there was no significant difference. The association of smoking with oral HPV prevalence may be stronger among women than men.

Conclusions:
Our findings suggest that smoking is importantly related to oral HPV infection. Local immunosuppressive effects of smoking may affect susceptibility to HPV infection and prolong the duration of virus infection in the oral cavity. These results imply that there would be a future potential risk factor and increase risk of oral and head and neck cancer.