title: Detection of human papillomavirus DNA sequences in oral squamous cell carcinomas and their relation to p53 and proliferating cell nuclear antigen expression.
abstract: BACKGROUND
  The etiology of oral squamous cell carcinoma (SCC) is still obscure. Since human papillomavirus (HPV) DNAs are associated with carcinoma of the uterine cervix, carcinomas of the oral cavity were investigated to ascertain if these viruses are present in squamous carcinomas of this anatomic site.
  
  
  METHODS
  Seventy-seven oral mucosal SCCs were examined for the presence of HPV DNAs by polymerase chain reaction and dot blot hybridization. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and p53 was performed and single strand conformation polymorphism analysis for p53 was undertaken. In situ hybridization detection of HPV-16 DNA also was performed.
  
  
  RESULTS
  Human papillomavirus-16 DNA was detected in 23 cases of oral SCC and both HPV-16 and HPV-18 DNA were detected in one case of tongue SCC. Human papillomavirus DNAs were detected of 11 of 33 tongue, 4 of 15 gingival, 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 retromolar region (0/2). Immunohistochemical examination for p53 was performed in 26 cases of oral SCC and the accumulation of p53 protein was 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 polymorphism analysis confirmed gene mutations in all 6 cases. Human papillomavirus-16 DNA was predominantly identified in cancer cells that showed a morphologic resemblance to basal cells and its hybridized signal in keratinized cells was reduced by in situ hybridization detection. Immunohistochemical detection of PCNA revealed its cooccurrence with HPV-16 DNA in cancer cells.
  
  
  CONCLUSIONS
  These results suggest that HPV-16 DNA sequences may have the capability to maintain the proliferative state of epithelial cells, and may contribute to the production of malignant phenotypes.
authors.affiliation: Department of Oral Pathology, Hokkaido University School of Dentistry, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shindoh
authors.forename: I
authors.initials: I
authors.lastname: Chiba
authors.forename: M
authors.initials: M
authors.lastname: Yasuda
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Funaoka
authors.forename: T
authors.initials: T
authors.lastname: Kohgo
authors.forename: A
authors.initials: A
authors.lastname: Amemiya
authors.forename: Y
authors.initials: Y
authors.lastname: Sawada
authors.forename: K
authors.initials: K
authors.lastname: Fujinaga
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D009154:Mutation; D027383:Papillomaviridae / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53