DETECTION OF HUMAN PAPILLOMAVIRUS DNA-SEQUENCES IN ORAL SQUAMOUS-CELLCARCINOMAS AND THEIR RELATION TO P53 AND PROLIFERATING CELL NUCLEAR ANTIGEN EXPRESSION

Background. The etiology of oral squamous cell carcinoma (SCC) is stil l obscure. Since human papillomavirus (HPV) DNAs are associated with c arcinoma of the uterine cervix, carcinomas of the oral cavity were inv estigated to ascertain if these viruses are present in squamous carcin omas of this anatomic site. Methods. Seventy-seven oral mucosal SCCs w ere examined for the presence of HPV DNAs by polymerase chain reaction and dot blot hybridization. Immunohistochemical detection of prolifer ating cell nuclear antigen (PCNA) and p53 was performed and single str and conformation polymorphism analysis for p53 was undertaken. In situ hybridization detection of HPV-16 DNA also was performed. Results. Hu man papillomavirus-16 DNA was detected in 23 cases of oral SCC and bot h HPV-16 and HPV-18 DNA were detected in one case of tongue SCC. Humin papillomavirus DNAs were detected of 11 of 33 tongue, 4 of 15 gingiva l, 2 of 4 palate, 2 of 5 buccal mucosa, 3 of 7 maxillary sinus, and 2 of 11 the floor of the mouth SCCs. None were detected in SCCs of the r etromolar region (0/ 2). Immunohistochemical examination for p53 was p erformed in 26 cases of oral SCC and the accumulation of p53 protein w as observed in 6 cases (i.e., in 4 of 17 HPV DNA-negative cases and in 2 of 9 HPV DNA-positive cases). Single strand conformation polymorphi sm analysis confirmed gene mutations in all 6 cases. Human papillomavi rus-18 DNA was predominantly identified in cancer cells that showed a morphologic resemblance to basal cells and its hybridized signal in ke ratinized cells was reduced by in situ hybridization detection. Immuno histochemical detection of PCNA revealed its cooccurrence with HPV-16 DNA in cancer cells. Conclusions. These results suggest that HPV-16 DN A sequences may have the capability to maintain the proliferative stat e of epithelial cells, and may contribute to the production of maligna nt phenotypes.