CHEMOPREVENTION OF CERVICAL CANCER WITH BETA-CAROTENE

宫颈癌是年轻女性常见的恶性肿瘤。这 肿瘤之前有一系列逐渐严重的发育不良。 病变(宫颈上皮内瘤变(CIN)I、II、III) 经过了充分的研究和刻画。强烈关联于特定的 人乳头瘤病毒(HPV)基因分型与宫颈上皮内瘤变和宫颈癌 已被记录在案。目前，CIN的治疗越来越多 积极的手术方式(从活检到子宫切除术)。我们的长期合作 目标是开发一种潜在的安全的医学预防疗法。 这些育龄妇女的可逆性创业。 大量的实验室和流行病学信息支持这一概念 维生素C、叶酸和β-胡萝卜素在调节中起作用 当然是CIN。我们的研究旨在确定低剂量(30毫克/天) β-胡萝卜素可调节宫颈可能的中间标志物 癌症风险。这些终点包括CIN程度、适当的状态 人乳头瘤病毒感染的HPV基因分型和形态特征， 即浅表角化细胞的凹陷细胞和角化不良，以及 将被连续监测。严格的资格标准一直是 确诊的CIN II和CIN III患者将接受β-胡萝卜素 长达两年的时间。主要终点将是CIN程度在6之后 几个月的β-胡萝卜素。试验成功的严格标准是 已经建立了。在疗程结束后，所有受试者 将监测停药治疗期间的复发率 记号笔也是。所有患者都将接受仔细的副作用评估。 和合规性。所有人的一般饮食和特殊营养状况 患者将接受监测，血浆维生素C、视黄醇、叶酸和β- 连续测定血浆和宫颈阴道脱落细胞中的胡萝卜素 也是。 基于这一有力和广泛的、随机和 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，随机的III期风险 将设计针对宫颈癌的减量试验。

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.