Diet and Duration of Cervical HPV Infection

在过去的五年中，我们建立了一个长期随访的多民族妇女队列，以确定影响宫颈人乳头状瘤病毒(HPV)感染持久性的因素。对我们数据的初步分析表明，减少饮食和血浆中某些微量营养素的水平，如类胡萝卜素，可能会增强致癌性HPV感染的持久性。尽管这种反向关联的确切机制尚不清楚，但未能清除病毒会导致促炎细胞因子的诱导，如白细胞介素1，这增加了细胞对DNA、蛋白质和脂肪损伤的脆弱性。我们假设，具有抗氧化剂和DNA修复特性的饮食成分将保护免疫细胞免受氧化损伤，并减少HPV的持久性。我们的具体目标是：1)评估饮食和/或血浆中类胡萝卜素、生育酚、维生素C和B复合维生素的浓度对致癌HPV感染、致癌HPV持续感染和宫颈sIL的影响；2)检测局部宫颈IL-1α、IL-1β和肿瘤坏死因子-α的mRNA水平对致癌HPV感染持续的影响；以及3)检查饮食和免疫标记物联合对宫颈致癌HPV感染持续的影响。将在五年内对751名致癌HPV DMA阳性妇女的多种族队列进行跟踪调查。访谈和生物标本将在基线和每隔四个月收集一次，在一年中至少四次访问，在五年中最多访问16次。每次就诊都会进行妇科检查，并收集以下标本：a)宫颈标本，用于细胞因子mRNA检测、HPV DNA分析、细胞学(Pap)涂片，以及未来检测沙眼衣原体和单纯疱疹病毒-2；b)空腹血液样本，用于测量微量营养素水平；c)宫颈标本，用于未来细胞因子蛋白检测；d)肛门样本，用于将来检测HPV。每次访问都将进行后续访谈；每年将重复一次节食史。对两个赠款周期收集的数据的统计分析将主要侧重于评估影响HPV感染持久性的饮食和血浆微量营养素水平和免疫特征。增加对营养和炎症反应在HPV持久性中的作用的了解将有助于我们更好地了解对HPV疫苗的反应性，可能有助于开发新的治疗方法，并可能提供更全面的宿主对HPV感染的反应。

During the past five years, we have established a multiethnic cohort of women for long-term follow-up to identify factors that influence the persistence of human papillomavirus (HPV) infection of the uterine cervix. Preliminary analyses of our data suggest that reduced dietary and plasma levels of certain micronutrients, such as carotenoids, may enhance the persistence of oncogenic HPV infection. Although the precise mechanism for this inverse association is unknown, failure to clear the virus results in the induction of proinflammatory cytokines, such as interleukin (IL)-1, which increases cellular vulnerability to DNA, protein and lipid damage. We hypothesize that dietary components that possess antioxidant and DNA repair properties will protect immune cells from oxidative damage and reduce HPV persistence. Our specific aims are to 1) evaluate the effect of dietary and/or plasma concentrations of carotenoids, tocopherols, vitamin C and B complex vitamins on incident oncogenic HPV infection, oncogenic HPV persistence, and SIL of the cervix; 2) examine the influence of local cervical mRNA levels of IL-1alpha, IL-1beta, and tumor necrosis factor (TNF)-alpha on the persistence of oncogenic HPV infection; and 3) examine the joint association of dietary and immunological markers on the persistence of oncogenic HPV infections of the cervix. A multiethnic cohort of 751 oncogenic HPV DMA-positive women will be followed during a five year period. Interviews and biological specimens will be collected at baseline and at four month intervals for a minimum of four visits in one year and a maximum of 16 visits in five years. At each visit a gynecologic examination will be performed and the following specimens will be collected: a) endocervical specimens for cytokine mRNA detection, HPV DNA analysis, a cytological (Pap) smear, and future detection of C. trachomatis and Herpes Simplex Virus-2; b) a fasting blood sample to measure micronutrient levels; c) an endocervical specimen by Merocel ophthalmic sponge for future cytokine protein detection; and d) an anal sample for future detection of HPV. A follow-up interview will be conducted at each visit; a diet history will be repeated annually. Statistical analyses of data collected in both grant cycles will focus primarily on the evaluation of dietary and plasma micronutrient levels and immune characteristics that influence the persistence of HPV infection. Increased knowledge of the role of nutrition and the inflammatory response in HPV persistence will help us to better understand the responsiveness to HPV vaccines, may assist in the development of novel therapies, and may provide a fuller picture of the host's reaction to HPV infection.