In situ hybridization for human papillomavirus as a method of predicting the evolution of cervical intraepithelial neoplasia.

Twenty-four women with cervical condylomata which were immunohistochemically positive for human papillomavirus (PV-Ag) (15 with CIN 1 and 9 with CIN 2) were followed for a period of 2-65 months. Fifty-seven biopsies were studied by the in situ hybridization (ISH) procedure for the detection of HPV 6/11 and 16/18 DNA. ISH positivity was found in 13/24 cases (54.2%); HPV 16/18 was evident in 7/9 CIN 2 (77.8%) as against 3/15 CIN 1 (20%) (P = 0.017) and in 8/13 cases with koilocytosis affecting up to 2/3 of the epithelial thickness (61.5%) as against 2/11 cases with koilocytosis affecting more than 2/3 of the epithelial layer (18.2%) (P = 0.03). Progression to CIN 3 occurred in 4 cases (2 CIN 1 and 2 CIN 2), the degree of dysplasia remained static in 5 cases (1 CIN 1 and 4 CIN 2) and regression occurred in 15 cases (9 CIN 1 and 6 CIN 2). The immunoperoxidase (IP) positive staining for PV-Ag persisted in 5/24 cases and disappeared in 19/24; 6/13 ISH positive cases maintained ISH positive and 7/13 became negative. The progression of dysplasia was significantly related to disappearance of the IP positivity (P less than 0.0001), to the ISH positivity (P = 0.05), to the persistence of ISH positivity (P = 0.008) and to HPV 16/18 positivity (P = 0.01). We believe that ISH positivity for HPV 16/18 in CIN 1 or 2 with low degrees of koilocytosis and conversion from PV-Ag positive to negative indicate a high risk of progression to CIN 3.