CHEMOPREVENTION OF CERVICAL CANCER WITH BETA CAROTENE

子宫颈癌是年轻女性常见的恶性肿瘤。 这 肿瘤发生之前，会出现一系列进行性更严重的发育异常 病变（宫颈上皮内瘤样病变（CIN）I、II、III）， 被充分研究和描述。 一个强关联的具体 人乳头瘤病毒（HPV）基因型与CIN和宫颈癌的关系， 被记录下来。 目前，CIN的治疗方法越来越多， 积极的手术方法（活检至子宫切除术）。 我们的长期 目的是开发一种安全的医学预防疗法， 这些育龄妇女的可逆性癌前病变。 大量的实验室和流行病学信息支持这一观点 维生素C、叶酸和β-胡萝卜素在调节 的CIN。 我们的研究旨在确定低剂量（30 mg/天） β-胡萝卜素可以调节宫颈癌的假定中间标志物， 癌症风险。 这些终点包括CIN的程度、适当的治疗状态、以及适当的治疗方法。 HPV基因型和乳头瘤病毒感染的形态学特征， 即挖空细胞症和浅表角化细胞的角化不良，和 将被连续监测。 严格的资格标准一直是 CIN II和III患者将接受β-胡萝卜素 长达两年 主要终点将是6天后的CIN程度。 几个月的β-胡萝卜素 试验成功的严格标准 确立了习 治疗期结束后，所有受试者 将在治疗结束后监测中度复发率 标记也是。 所有患者都将接受仔细的副作用评估 和遵守。 所有人的一般饮食和特定营养状况 将对患者进行监测，并监测血浆维生素C、视黄醇、叶酸和β- 在血浆和宫颈阴道脱落细胞中连续测定胡萝卜素 也 根据这一有力的和广泛的，随机的， 安慰剂对照，癌症控制II期试验的调制 CIN的中间生物学终点，随机III期风险 将设计宫颈癌的减少试验。

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.