A randomized, double blind, phase III trial using oral beta-carotene supplementation for women with high-grade cervical intraepithelial neoplasia

Ka. Keefe et al., A randomized, double blind, phase III trial using oral beta-carotene supplementation for women with high-grade cervical intraepithelial neoplasia, CANC EPID B, 10(10), 2001, pp. 1029-1035
Citations number
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
ISSN journal
1055-9965 → ACNP
Year of publication
1029 - 1035
SICI code
To evaluate the effect of daily beta -carotene (30 mg) versus placebo over a 2-year period on cervical intraepithelial neoplasia (CIN) 2 and 3 lesions . Human papillomavirus (IPV) typing was done to determine whether lesion re gression was related to HPV. Micronutrient levels were measured to determin e whether levels were predictive of regression. Variables that influence th e risk of HPV infection and CIN, such as cigarette smoking and sexual behav ior, were evaluated. Women were randomized to beta -carotene or placebo, wi th cytology and colposcopy every 3 months. Cervical biopsies were performed before treatment and after 6 and 24 months to evaluate response. Persisten ce of or progression to CIN 3 resulted in removal from the study, whereas t reatment continued for 2 years on all others. The presence and type of HPV was determined by PCR. Response was defined as an improvement in CIN by 2 g rades. Mantel-Haenszel chi (2) test was used to analyze response to treatme nt. Fisher's exact test was used to determine the effect of HPV and CIN gra de on response Wilcoxon's rank-sum tests were used to compare micronutrient levels between groups. Twenty-one of 124 enrolled women were not randomize d because they either moved, became pregnant, voluntarily withdrew, or the pathological review of their initial cervical biopsies did not confirm CIN 2 or 3. Of the remaining 103 women, 33 experienced lesion regression, 45 ha d persistent or progressive disease, and 25 women did not complete the stud y and were considered nonresponders in the final analysis. The overall regr ession rate (32%) was similar between treatment arms and when stratified fo r CIN grade. Data on 99 women with HPV typing showed that 77% were HPV-posi tive and 23% HPV-negative at enrollment. HPV-positive lesions were subdivid ed into indeterminate-, low-, and high-risk categories; the response rate w as highest for women with no HPV detected (61%), lower for indeterminate/lo w-risk (30%), and lowest for high-risk (18%; P = .001). CIN regression was negatively correlated with retinol levels. In conclusion, beta -carotene do es not enhance the regression of high-grade CIN, especially in HPV-positive subjects.