A research for the relationship between human papillomavirus and human uterine cervical carcinoma. I. The identification of viral genome and subgenomic sequences in biopsies of Chinese patients.

Biopsies from 318 cases with squamous cell carcinoma of the uterine cervix, 48 with cervical and vulvar condylomata, 14 with cervical intraepithelial neoplasia (CIN), 34 with chronic cervicitis and 24 with normal cervical epithelium were collected from different geographic regions with different cervical cancer mortalities. The DNA.DNA dot-blot and Southern blot hybridization results show that there is a close relationship between HPV-16 and the uterine cervical squamous cell carcinoma in China. One very interesting observation is that the finding of HPV-16-homologous DNA differs significantly among five geographic regions, and corresponds with the mortalities from cervical cancer of these five regions. HPV-11 was found mainly in benign lesions. The rate of detection of HPV-16 in Chinese women increased from 8.3% in normal cervical epithelium to 20% in chronic cervicitis, 28% in cervical condyloma, 50% in CIN and 60.4% in cervical cancer. It is suggested that HPV-16 infection may be an etiological factor in the development of human cervical carcinoma. From the results of Southern blot hybridization, it appeared that HPV-16 DNA had been integrated into the genome of the host cell in cervical cancer. Whereas the HPV-16 DNA sequence was only present as an episome in normal cervical epithelium and cervical benign lesions. The rate of occurrence of E6-E7 genes is the highest (88.9%) compared with that of other subgenomic fragments of HPV-16 in specimens of human cervical cancer in China. This implies that E6 and E7 may be the oncogenic genes of HPV-16 and play an important role in the carcinogenesis of human cervical epithelial cells. The amplification and rearrangement of the c-myc protooncogene are closely associated with the occurrence of cervical cancer. The results presented here revealed that the activated c-myc oncogene may cooperate with HPV-16 in the carcinogenic processes.