Diet and Duration of Cervical HPV Infection

在过去的五年中，我们建立了一个多种族的妇女队列进行长期随访，以确定影响宫颈人乳头瘤病毒（HPV）感染持续性的因素。对我们数据的初步分析表明，某些微量营养素（如类胡萝卜素）的饮食和血浆水平降低可能会增强致癌HPV感染的持续性。虽然这种反向关联的确切机制尚不清楚，但未能清除病毒导致诱导促炎细胞因子，如白细胞介素（IL）-1，这增加了细胞对DNA，蛋白质和脂质损伤的脆弱性。我们假设，具有抗氧化和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和复合维生素B对致癌HPV感染、致癌HPV持续性和宫颈SIL的影响; 2）检测宫颈局部IL-1 α、IL-1 β和肿瘤坏死因子（TNF）-α mRNA水平对致癌HPV感染持续性的影响;和3）检查饮食和免疫学标记物对宫颈致癌HPV感染持续性的联合关联。将在5年期间对751名致癌HPV DMA阳性女性的多种族队列进行随访。将在基线和每4个月采集一次访谈和生物样本，1年内至少进行4次访视，5年内最多进行16次访视。每次访视时，将进行妇科检查，并采集以下标本：a）宫颈内标本，用于细胞因子mRNA检测、HPV DNA分析、细胞学（Pap）涂片和未来的C.沙眼和单纯疱疹病毒-2; B）测量微量营养素水平的空腹血液样品; c）用于将来细胞因子蛋白检测的Merocel眼用海绵的宫颈内样本;和d）用于将来HPV检测的肛门样品。每次访视时将进行随访;每年重复一次饮食史。对两个资助周期收集的数据进行统计分析，将主要侧重于评估影响HPV感染持续性的饮食和血浆微量营养素水平以及免疫特征。增加对营养和炎症反应在HPV持续性中的作用的了解将有助于我们更好地了解HPV疫苗的反应性，可能有助于开发新的治疗方法，并可能提供宿主对HPV感染反应的更全面的了解。

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.