Cellular manifestations of human papillomavirus infection in the oral mucosa

Background and Objectives: Human papillomavirus infection has been suggeste d to play a role in the development of epithelial carcinomas, particularly those of the uterine cervix. Less information is available on the role of t he virus in oral lesions. It has been proposed that the viral oncoproteins specifically complex with the products of cellular tumor suppressor gene, n amely E6 with p53 and E7 with retinoblastoma gene product. Inactivation or mutation in p53 gene is also known to result in loss of control over the ce ll cycle and increases in tumor proliferation rates. The present study exam ines the role of HPV infection in relation to p53 and the extent of the tum or proliferative compartment reflected by cyclin D1 and Ki-67 expression du ring various phases of tumor progression in the oral epithelium. Method: Nonisotopic in situ hybridization (NISH) was performed to detect HP V 6/11 and 16/18. Expression of p53, cyclin D1, Ki-67, and the HPV 16/18 E6 protein were detected by immunocytochemistry. Results: There was significant correlation between the extent of histologic al abnormality and HPV infection. A correlation (r = 0.250, P = 0.0089) was evident between the presence of HPV 16 and occurrence of invasive cancer. Expression of the tumor suppressor p53 protein also showed significant posi tive correlation with histology (r = 0.475, P = 0.00004). The tumor prolife rative fraction also increased with the extent of histological abnormality (r = 0.387, P = 0.0003 for cyclin D1 and r = 0.463, P = 0.0001 for Ki 67). Accumulation of p53 and increase in tumor proliferation also correlated to the presence of HPV infection (r = 0.511, P = 0.00003 for p53; r = 0.478, P = 0.00002 for cyclin D1 and r 0.521, P = 0.00004 for Ki-67). Conclusions: The present study thus demonstrates the importance of HPV infe ction in oral tissue. Expression of the high-risk HPV 16/18 E6 protein also appears to be a critical event along with aberrant p53 expression. These r esults are of significance to the molecular epidemiology of oral cancer and may also be used to supplement and elaborate the diagnosis of Oral lesions . J. Surg. Oncol. 1999;71:10-15. (C) 1999 Wiley-Liss, Inc.