Several nutrients and dietary factors appear to be important in determining risk for cervical cancer. Evidence from epidemiologic studies strongly supports a role for a diet emphasizing fruits and vegetables, which provides carotenoids among an array of nutrients and other possibly protective factors, in promoting the regression of cervical intraepithelial neoplasia (CIN). Previous trials or interventions to reverse cervical dysplasia have focused on pharmacologic agents or dietary supplementation, but the most promising and least studied potential chemopreventive strategy is diet. The primary aim of the study is to determine if a carotenoid- rich diet high in fruits and vegetables will promote a significant increase in the regression rate of CIN I and CIN II. In order to understand the potential mechanism of the dietary intervention, the secondary aims are: to determine if the regression of CIN I and ll is reflected in the modulation of viral genome copy number of human papilloma virus (HPV) and HPV E6/E7 expression; and to determine if the regression of CIN I and II is associated with expression of retinoic acid receptors (RAR) and/or retinoid X receptors (RXR). HPV has clearly been determined to be a causal agent for CIN, therefore, it is essential to understand the impact of diet on HPV as a possible mechanism of action. A biological effect may be mediated by binding to specific nuclear protein receptors, RAR and RXR. These receptors regulate expression of specific target genes, therefore, they have been included to explore the possible mechanism of action. In order to achieve the above aims, a clinical trial of a carotenoid-rich diet high in fruits and vegetables is proposed among 326 women with CIN I and II. The primary endpoint will be the complete regression of CIN, based on biopsy specimens taken at baseline and end of study. The rates of regression will be compared between those women on the dietary intervention versus women continuing their usual diet. The sample size was determined assuming a base spontaneous regression rate of 25%, a 30% dropout rate (primarily nonadherence), a 10% novel HPV type (precluding study of mechanism), and available patient population for accrual. Dietary intake will be measured using the Fred Hutchinson Food Frequency Questionnaire and 7-Day Food Records. The women on the treatment arm of study will receive individualized dietary counseling with behavioral tactics to facilitate dietary changes. The goal of the dietary intervention is the simplest changes to achieve a fruit and vegetable intake that will result in plasma betacarotene >0.69 and sum of carotenoids >2.01 umol/L. Findings of this study may enable physicians to use diet as a management strategy for CIN, which would eliminate the need for millions of ablative procedures that are done each ear for CIN.
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