Epstein-Barr virus in the proliferative diseases of squamous epithelium in the oral cavity.

The presence of Epstein-Barr virus was analyzed in 79 cases of oral epithelial proliferative diseases by polymerase chain reaction, in situ hybridization for Epstein-Barr virus-deoxyribonucleic acid and Epstein-Barr virus-encoded small messenger ribonucleic acid and immunohistochemistry for Epstein-Barr virus latent membrane protein. These lesions were histologically categorized as invasive squamous cell carcinoma (n = 36), carcinoma in situ (n = 10), verrucous carcinoma (n = 4), leukoplakia (n = 19), and papilloma (n = 10). Epstein-Barr virus genomes were detected in 19 squamous cell carcinoma (52.8%), four carcinoma in situ (40%), and one leukoplakia (5.3%); none of the verrucous carcinoma or papilloma cases were positive with polymerase chain reaction. By deoxyribonucleic acid in situ hybridization, positive signals were observed in the nuclei of cancer cells in 10 cases, in infiltrating lymphocytes in three, and both in one case. In patients with carcinoma in situ, only a single case was positive. In one case of leukoplakia positive signals were found in upper and middle layer squamous cells. The results by Epstein-Barr virus-encoded small messenger ribonucleic acid in situ hybridization revealed the same distribution as that by deoxyribonucleic acid in situ hybridization. Latent membrane protein was expressed only in the epithelial cells of leukoplakia but not in cases with squamous cell carcinoma and carcinoma in situ. These findings suggest that Epstein-Barr virus infection of oral squamous epithelium may be carcinogenic; alternatively, the virus may merely exist in epithelial cells of squamous cell carcinoma, carcinoma in situ, and leukoplakia as a passenger.