Detection of HPV and ras gene mutations in cervical smears from female genital lesions.

The collaboration of ras oncogenes with HPV E6/E7 genes inducing full transformation of cervical keratinocytes has been suggested. The purpose of this study was to detect and type HPV by PCR and to assess the extent of involvement of the ras oncogene activation by point mutations in cervical premalignant and malignant lesions, using stained PAP cervical smears. Specimens were obtained from 35 women with genital lesions, and codon 12 point mutations of the K-ras and H-ras oncogenes were detected, as well as HPV18 at a higher rate than HPV16 (48% vs 10%) in cervical lesions by PCR-RFLP and PCR analysis, respectively. Our study indicates that the mutational activation of the K-ras gene may be involved in the development of a small subset of cervical carcinomas and that mutationally activated ras oncogenes cooperate with HPV in the early stages of carcinogenesis in the cervix of the uterus.