High prevalence of HPV18 in correlation with ras gene mutations and clinicopathological parameters in cervical cancer studied from stained cytological smears.

The multi-event nature of carcinogenesis has led to extensive studies of oncogenes, onco-suppressor genes and viruses involved in human cancers. The collaboration of ras oncogene with HPV E6/E7 genes inducing full transformation of cervical keratinocytes has also been suggested. The purpose of this study was to detect the presence of codon 12 point mutations of ras genes, as well as to detect and identify the human papillomaviruses in stained smears of cervical malignancies and to correlate them with the clinicopathological parameters of the Greek patients. Specimens were obtained from 88 women, codon 12 point mutations of the K-ras (30%) and H-ras (10%) oncogenes, as well as HPV18 were detected at a higher rate than HPV16 (66% vs 7%) in cervical lesions by PCR-RFLP and PCR analysis, respectively. The statistical analysis of the data demonstrates correlation between the presence of K-ras mutations and FIGO stage and between FIGO stage and survival of the patients. It is suggested that ras activation combined with HPV infection may be an important step in the carcinogenesis of a substantial number of cervical carcinomas.