Human Papillomavirus Integration into the Host Cell Genome during the Developmental Stage of Cervical Cancer

Abstract

The infectivity of human papillomavirus (HPV) is closely linked to characteristics of epithelial lesions in the uterine cervix. In our previous study, we reported amplification of c-myc gene, and pointed out the possibility that tumorigenesis might be enhanced by the amplification of this oncogene. Furthermore, we found that HPV exists in the host cell in various forms, such as the Episome or Integration form. Based on these results, we proposed the hypothesis that the chromosomal integration of HPV-DNA (deoxyribonucleic acid) might play a significant role in tumorigenesis of cervical cancer. In order to substantiate this hypothesis, we studied the state of HPV-DNA in tissue samples of patients with condyloma acuminatum, mild dysplasia or invasive carcinoma using a two-dimensional Southen hybridization technique. The HPV-DNA types found were: HPV6 in one patient with condyloma acuminatum, HPV16 in thirteen patients with mild dysplasia or invasive carcinoma, and HPV18 in two patients with invasive carcinoma. As for the form of HPV in host cells, it was notewothy that the DNA in all cases of benign lesions such as condyloma acuminatum and mild dysplasia existed as Episomes, whereas the DNA in 11 out of 12 cases of invasive carcinoma was Integrations.