Oncogene activation: an informative marker for the human papillomavirus-lesions severity

The aim of this study was the detection of c-Ha-ras and c-myc activation and p21ras and p62myc expression in anogenital HPV-associated lesions. Thirty-two women with cervical and vaginal lesions and forty men with anal or penile warts were enrolled for the study. Biopsies were subjected to histological assessment, in situ hybridization with biotinylated probes, and immunohistochemistry. In both women and men, most of the biopsies showing no major histological abnormalities were negative for HPV detection. The low-grade squamous intraepithel-)ial lesions (SIL) harbored HPV in more than 50% of cases. The high-grade SIL contained mostly oncogenic HPV. C-Ha-ras and c-myc activation was detected in 31/41 HPV-positive lesions, especially in lesions harboring HPV 31/35/51 or multiple HPV. Simultaneous activated oncogenes were found in 7 out of 9 high-grade SIL and in 21 out of 45 low-grade SIL. In most of the lesions, we demonstrated concurrent detection of p21ras and p62myc proteins and oncogene activation. Our study shows that c-Ha-ras and c-myc activation is correlated with oncoprotein expression and associated with the presence of oncogenic HPV. Such activation might play a role in the development of high-grade anogenital dysplasia.