H-RAS ONCOGENE MUTATION AND HUMAN PAPILLOMAVIRUS INFECTION IN ORAL CARCINOMAS

Objective: Previous in vitro studies have demonstrated that transfecti on of an activated uas gene induces malignant transformation in epithe lial cell lines infected with the human papillomavirus (HPV). The resu lts of these studies support the hypothesis that HPV may cooperate wit h an activated vas gene in epithelial tumor carcinogenesis. To test th is hypothesis in head and neck cancers, we screened 35 oral carcinomas for the presence of HPV DNA and for a mutated H-ras gene. Design: The design of the study was a screening survey type. Twenty-seven oral sq uamous cell carcinomas and eight verrucous carcinomas were analyzed fo r the presence of HPV DNA using the polymerase chain reaction, followe d by Southern blot and probe hybridization. The tumors were also scree ned for point mutations of the H-ras gene using the polymerase chain r eaction 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 positi ve for HPV DNA, with three tumors (11%) demonstrating both HPV DNA and H-ras gene point mutation. While the rate of simultaneous HPV infecti on and uns gene activation by point mutation was 11% in oral squamous cell carcinomas, 25% of oral verrucous carcinomas contained both HPV D NA and mutation in the H-ras gene. Conclusions: These results suggest a stronger association between HPV infection and activation of the H-r as gene in oral verrucous carcinomas. These results continue to confir m the multihit hypothesis of tumorigenesis and suggest that in some ca ses of oral cancer at least two of these events are H-ras gene mutatio n and HPV infection.