Reviewing the role of human papillomavirus in oral cancer using the Bradford Hill criteria of causation.

Human papillomavirus is a well-established risk factor for oropharyngeal cancer, although its role in oral cancer is still debated. Inconclusive evidence of its role in oral cancer is due to conflicting data arising from methodological differences, mostly due to the use of diagnostic tests with varying sensitivity and specificity. In addition, there is a lack of experimental data linking HPV to oral cancer. Recent epidemiological studies provide data on HPV prevalence in oral squamous cell carcinoma and other potentially malignant oral disorders. Further, molecular data from in vivo and in vitro models have led to new insights into the role of human papillomavirus in oral cancer. The clinical significance of identifying HPV as an etiology for oral squamous cell carcinoma is that if proven, vaccination could be an effective prevention tool. Further, like oropharyngeal squamous cell carcinoma, prognostic differences may exist between human papillomavirus positive and negative oral squamous cell carcinoma. This manuscript reviews data from the published literature using Bradford Hill criteria of causation to assess the role of human papillomavirus in oral cancer. Due to the advancement in molecular biology, the requirements of each of the Bradford Hill criteria of causation are modified to include integrated data from both epidemiological studies and experimental studies exploring molecular carcinogenesis.