Distribution pattern of human papilloma virus 16 genome in cervical neoplasia by molecular in situ hybridization of tissue sections

Using a highly sensitive method with single-stranded RNA probes, we analyzed the distribution pattern of HPV 16 DNA by in situ hybridization in CIN 11 (10 cases), CIN III (11 cases) and in invasive cervical carcinoma (17 cases). The technique used detected as little as 20–50 viral genomes per cell. This sensitive technique unmasked HPV 16 genomes in the basal cells of all forms of CIN. In CIN III viral genomes were present throughout the entire thickness of the epithelium. There was a striking difference in the distribution of viral DNA in CIN II compared with CIN III and invasive cancer. Variable viral genome distribution was observed in CIN II with the highest copy number in the area of epithelial differentiation. In contrast, CIN III showed a uniform distribution pattern of HPV genomes reflecting the lack of epithelial maturation. The majority of invasive carcinomas showed the same uniform distribution of the HPV 16 genomes as CIN III.