CHEMOPREVENTION OF CERVICAL CANCER WITH BETA CAROTENE

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Cancer of the uterine cervix is a common malignancy in young women. This tumor is preceded by a sequence of progressively more severe dysplastic lesions (cervical intraepithelial neoplasia (CIN) I, II, III) which have been well-studied and characterized. A strong association of specific genotypes of human papillomavirus (HPV) with CIN and cervical cancer has been documented. Currently CIN is treated with progressively more aggressive surgical approaches (biopsy to hysterectomy). Our long-term goal is to develop a safe medical preventive therapy of this potentially reversible preneoplasia in these women of child-bearing age. Substantial laboratory and epidemiologic information supports the notion that vitamin C, folic acid, and beta-carotene play a role in the modulation of CIN. Our study is designed to determine whether a low dose (30mg/day) of beta-carotene can modulate putative intermediate markers of cervical cancer risk. These endpoints include degree of CIN, status of appropriate HPV genotypes, and morphologic features of the papillomavirus infection, namely koilocytosis and dyskeratosis of superficial keratinizing cells, and will be monitored serially. Strict eligibility criteria have been established and patients with CIN II and III will receive beta-carotene for up to two years. The primary endpoint will be degree of CIN after 6 months of beta-carotene. Strict criteria for success of the trial have been established. Following the end of the treatment period all subjects will be monitored off therapy for rate of recurrence of intermediate markers as well. All patients will be evaluated carefully for side effects and compliance. The general dietary and specific nutrient status of all patients will be monitored and plasma vitamin C, retinol, folate and beta- carotene measured serially in plasma and exfoliated cervico-vaginal cells as well. Based on the results of this vigorous and extensive, randomized and placebo-controlled, cancer control phase II trial of the modulation of intermediate biological endpoints of CIN, a randomized phase III risk reduction trial for cervical cancer will be designed.