H-ras oncogene mutation and human papillomavirus infection in oral carcinomas.
OBJECTIVE
Previous in vitro studies have demonstrated that transfection of an activated ras gene induces malignant transformation in epithelial cell lines infected with the human papillomavirus (HPV). The results of these studies support the hypothesis that HPV may cooperate with an activated ras gene in epithelial tumor carcinogenesis. To test this hypothesis in head and neck cancers, we screened 35 oral carcinomas for the presence of HPV DNA and for a mutated H-ras gene.


METHODS
The design of the study was screening survey type. Twenty-seven oral squamous cell carcinomas and eight verrucous carcinomas were analyzed for the presence of HPV DNA using the polymerase chain reaction, followed by Southern blot and probe hybridization. The tumors were also screened for point mutations of the H-ras gene using the polymerase chain reaction and restriction fragment length polymorphism analysis.


RESULTS
Six (22%) of the 27 oral squamous cell carcinomas demonstrated point mutation in the H-ras gene. In addition, six tumors (22%) were positive for HPV DNA, with three tumors (11%) demonstrating both HPV DNA and H-ras gene point mutation. While the rate of simultaneous HPV infection and ras gene activation by point mutation was 11% in oral squamous cell carcinomas, 25% of oral verrucous carcinomas contained both HPV DNA and mutation in the H-ras gene.


CONCLUSIONS
These results suggest a stronger association between HPV infection and activation of the H-ras gene in oral verrucous carcinomas. These results continue to confirm the multihit hypothesis of tumorigenesis and suggest that in some cases of oral cancer at least two of these events are H-ras gene mutation and HPV infection.
Anderson
J A
JA
Department of Otolaryngology, University of Toronto, Ontario.
Irish
J C
JC
McLachlin
C M
CM
Ngan
B Y
BY
D000328:Adult; D000368:Aged; D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D018289:Carcinoma, Verrucous / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D003043:Cocarcinogenesis; D004279:DNA, Viral / Q000032:analysis*; D003625:Data Collection; D006801:Humans; D008403:Mass Screening; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000150:complications* / Q000175:diagnosis / Q000517:prevention & control; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012307:Risk Factors; D015996:Survival Rate; D014162:Transfection; D014412:Tumor Virus Infections / Q000150:complications* / Q000175:diagnosis / Q000517:prevention & control
D004279:DNA, Viral; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)