Prevalence of human papillomavirus16 DNA and p16INK4a protein in oral squamous cell carcinoma: A systematic review and meta-analysis

BACKGROUND AND AIM Indian patients with oral squamous cell carcinoma (OSCC) are etiologically associated with the use of tobacco and alcohol; yet, a proportion of tumors that may harbor human papillomavirus (HPV) infections cannot be neglected. The following meta-analysis was conducted to address the association of p16INK4a and HPV DNA with OSCC. In addition, the study also provides the updated prevalence of HPV-induced OSCC. MATERIALS AND METHODS Literature survey was performed using databases such as PubMed with the help of the following keywords - "HPV infection," "oral squamous cell carcinoma," "p16INK4a," "HPV DNA," "E6," "E7," "L1," "L2" and "LCR." Proportion method was performed to derive the forest plot using MedCalc statistical software version 16.4.3. RESULTS Among 145 research articles, 33 articles were selected for further analysis, in which 13 articles were related to HPV DNA detection in tissues, 11 articles detected the overexpression of p16INK4a and nine articles reported the detection of both HPV DNA and p16INK4a expression. Meta-analysis revealed significant heterogeneity (P < 0.0001) among the articles. Overall, the study consisted of 3339 patients with OSCC, among which 559 patients were diagnosed with the presence of HPV16 DNA with a random proportion of 20.1% at 95% confidence interval (CI) (13.9-27.1, P < 0.0001). Overexpression of p16INK4a protein was observed in 709 patients with a random proportion of 25.4% at 95% CI (14.3-38.3, P < 0.0001). CONCLUSION HPV DNA and expression of p16INK4a was suggested as gold standard for the detection of HPV infection in many cases of cancers. Frequency of HPV infection is significantly higher in patients with OSCC as identified through the detection of HPV DNA and p16INK4a expression. Even though the association of HPV infection has been established in head and neck cancer, this review could further the establishment of molecular level interaction of HPV in patients with oral cancer.