Association of Human Papillomavirus (HPV) Infection with Oral Cancer: Review of Recent Research

Abstract

Human papillomavirus (HPV) infection is a major risk factor for cervical cancer, and may also be associated with the development of oropharyngeal cancer and prognosis of affected patients. However, the causal relationship between HPV infection and oral cancer has not been fully elucidated. In this review, we examined recent results of epidemiologic and basic research studies to elucidate risk factors associated with oral HPV infection, HPV prevalence in oral cancer patients, and the characteristics of the molecular mechanism of HPV-positive oral cancer. We found that HPV DNA was positive in 4.0-32.0% of oral cancer cases, with HPV16 being a common high-risk type found in oral cancer specimens. Also, the rate of HPV16-positivity was higher in epithelial dysplasia lesion and oral squamous cell carcinoma samples compared with normal epithelial tissues, suggesting that HPV16 is involved in oral cancer development. A low percentage of oral cancer cases showed E6 and E7 mRNA-positivity, and the positive rates of E6 and E7 mRNA were lower than those of HPV DNA; thus, we suggest that molecular mechanisms independent of stable E6 and E7 expression may be involved in the malignant transformation of HPV-related oral cancer (i.e., oral cancer caused by oral HPV infection). Although HPV16-positive oral cancers were associated with a better prognosis compared with HPV16-negative oral cancers, it remains unclear whether HPV-related oral cancers are associated with a better prognosis. Since oral HPV infection is associated with poor oral hygiene, oral health care and smoking cessation may play significant roles in its prevention. For the development of evidence-based prevention strategies for the treatment of HPV-related oral cancer, it is necessary to clarify the significance of the existence and role of HPV in HPV DNA-positive oral cancer. It is strongly anticipated that the results of basic and clinical studies of oral HPV infection will be presented in the near future.