Integration of human papillomavirus types 16 and 18 in cervical epithelial lesions using tyramide-amplified in situ hybridization

[Abstract] Highly sensitive in situ hybridization (ISH) and highly sensitive PCR methods were used to determine the infection of HPV type 16 (HPV 16) and type 18 (HPV 18) and the integration of them into the cells of squamous and glandular lesions of the uterine cervix. The frequency of HPV infection detected by ISH and PCR increased with progression of squamous lesions. All cases of ICC showed the integrated pattern of positive signals with ISH and all positive cases in CIN1 showed the episomal pattern. In CIN2 episomal patterns were more frequent than integrated pattern and in CIN3 integrated pattern were more frequent. Glandular lesions showed a greater frequency of HPV 18 than HPV 16 on nested PCR and ISH, and almost all of ISH-positive cases showed the integrated pattern. These data suggested that integration of HPV 16 and 18 is required for carcinogenesis in both squamous cell carcinoma and adenocarcinoma of the uterine cervix.