title: Epstein-Barr virus (EBV)-related oral squamous cell carcinoma in Okinawa, a subtropical island, in southern Japan--simultaneously infected with human papillomavirus (HPV).
abstract: Up to now, many authors have reported on the EBV infection and its carcinogenic importance in undifferentiated nasopharyngeal carcinoma (WHO classification, type III), but the infection of the virus in well differentiated oral squamous cell carcinoma has not been well described. We introduce the EBV-related well differentiated oral squamous cell carcinomas in Okinawa, a subtropical island in the southernmost part of Japan. This study aimed to clarify the pathogenesis of this malignancy in this area by carrying out analysis of the histology and the Epstein-Barr (EBV) and human papillomavirus (HPV) infection. In the Department of Oral Surgery, Ryukyu University Hospital Okinawa, 188 cases of oral malignant tumours were encountered from 1996 to 2000. The histopathological examination and the sequence analysis of LMP-1 carboxy terminal region and EBNA2 region of EBV were carried out, as were the analysis of virus subtypes, A and B, BamHI-F and f, and C and D. Additionally, HPV infection in the squamous cell carcinomas were demonstrated using E6 and E7 region primer sets by PCR method. In Okinawa, 94% (177/188) of the cases were squamous cell carcinomas. A surprisingly large number of EBV (72%) and HPV (78%) infections in the oral squamous cell carcinomas were demonstrated. EBV type B virus infection was found in 36% of EBV-related oral squamous cell carcinoma in Okinawa, but in only 2-5% of the mainland cases. In both regions the incidence of the BamHI- f variant infection was very low. The infected virus in 79 out of 80 (39 Okinawan and 41 mainland) cases was BamHI- F type. In Okinawa, the numbers of C and D variants were almost equal, whereas in the mainland the D variant was rare. Further, a 30 bp deletion in LMP-1 gene was frequently demonstrated in Okinawan and mainland cases of type A virus, but not in type B virus. Lastly, single nucleotide mutations in EBNA2 region of type A virus when compared with B95-8 strain were demonstrated in Okinawan cases. The prognosis for (mostly EBV/HPV infected) squamous cell carcinomas in Okinawa was better than that in the mainland where most cases were negative for EBV and/or HPV.
authors.affiliation: Department of Pathology, Ryukyu University School of Medicine, 207 Uehara, Nishihara, Okinawa 903-0215, Japan. igbucho@jim.u-ryukyu.ac.jp
authors.forename: Mayumi
authors.initials: M
authors.lastname: Higa
authors.forename: Takao
authors.initials: T
authors.lastname: Kinjo
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kamiyama
authors.forename: Katsuni
authors.initials: K
authors.lastname: Chinen
authors.forename: Teruo
authors.initials: T
authors.lastname: Iwamasa
authors.forename: Akira
authors.initials: A
authors.lastname: Arasaki
authors.forename: Hajime
authors.initials: H
authors.lastname: Sunakawa
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000453:epidemiology / Q000473:pathology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D016679:Genome, Viral; D005838:Genotype; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications* / Q000453:epidemiology / Q000473:pathology; D017354:Point Mutation; D014412:Tumor Virus Infections / Q000150:complications / Q000453:epidemiology / Q000473:pathology; D014763:Viral Matrix Proteins / Q000235:genetics; D014764:Viral Proteins
chemical_list: C402641:EBNA-2 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D014763:Viral Matrix Proteins; D014764:Viral Proteins