Evolution of human papillomavirus infections in the uterine cervix during a long-term prospective follow-up.

Abstract

A series of 513 women presented with cervical human papillomavirus (HPV) infections (with or without cervical intraepithelial neoplasia; CIN) have been prospectively followed up since 1981 (mean 25.6 months), at 6-month intervals, by colposcopy with PAP smears and/or punch biopsies. The latter were analyzed by light microscopy, as well as immunohistochemically for HPV structural proteins. HPV DNA typing was accomplished by Southern blot, spot, and in situ hybridization techniques using the DNA probes for HPV 6, 11, 16, 18 and 31. Of the 513 lesions, 24.8% regressed, 59.8% persisted, and 14.1% progressed, 11.9% having been coned due to progression to carcinoma in situ (CIS). So far, 1.1% of lesions have recurred after such a treatment. The natural history was significantly associated with the grade of CIN (HPV-NCIN versus HPV-CIN, p less than 0.01). The progression rate was highest (33.3%) and regression lowest (5.6%) in HPV 16 lesions. All the recurrent lesions disclosed HPV 16 DNA, this type being found most frequently in the severest lesions (CIN III). Depending on the hybridization technique used, changes in HPV type were found in 11-17% of the lesions during the follow-up. Noteworthy is the discovery of all the HPV types also in biopsies with no signs of HPV infection on light microscopy, suggesting a latent HPV infection in these 'regressor' lesions. The results confirm that cervical HPV infections show a natural history comparable to that of classical CIN. Although the high-risk character of HPV 16 (and HPV 18) was clearly established, the inherent potential for progression (25.6%) of the HPV 6/11 lesions should not be neglected in therapeutic considerations.