Dysplasia of the uterine cervix is a recognized preneoplastic condition. Because of the observed ability of retinoids to reverse other dysplastic conditions in vitro and in vivo, a number of clinical studies have been carried out of the effect of these agents on cervical dysplasia, with the object of developing a means of chemoprevention of cervical malignancies in women at risk. We have conducted phase I and II trials of topical tretinoin (retinoic acid and Retin-A) delivered by means of a cervical cap and inert collagen sponge system. The results of these studies warranted a phase III trial, which is now underway. The outcome of the latter investigation will have important implications, not only for the management of patients with cervical dysplasia but also for therapeutic approaches to other precancerous conditions.

Retinoids are effective suppressors of the phenotypic development of cancer in many animal systems, whether the process is initiated by chemical, physical or viral carcinogens. Cases of cervical intraepithelial neoplasia are excellent for studying the effectiveness of retinoids as chemopreventive agents because the process can be closely followed by serial colposcopic and pathologic (cytology or biopsy) means and changes in the condition safely monitored. We have previously conducted a phase I study of trans-retinoic acid (Tretinoin) given topically by a collagen sponge and cervical cap. A dose of 0.372% was selected for phase II trial. We have treated 20 patients with topical retinoic acid, and a complete response with total regression of disease was obtained in 50%. Systemic and cervical side effects were mild and vaginal side effects moderate but tolerable. These results provide a clinical basis for a randomized, double-blind phase III study to definitely answer the question of whether retinoic acid is an effective chemopreventive agent for cervical cancer.