Vitamin D and Natural History of Human Papillomavirus (HPV) Infections in Women

项目描述 与高危（hr）HPV持续性与一过性相关的辅助因素尚未明确定义。缺陷 维生素D等营养素可通过DNA损伤，免疫功能不全， 和基因改变。虽然最近的一项研究报告说，维生素D缺乏与 普遍hrHPV感染的可能性增加，据我们所知，没有研究探讨相关性 维生素D水平和hrHPV持续或再激活之间的关系。从2011年到2012年，我们招募了409名健康 中年妇女参加为期6个月的hrHPV感染纵向研究。每个月，女性自我- 收集阴道样本进行基于PCR的基因型特异性hrHPV DNA检测，并完成健康检查， 性行为问卷此外，收集血清用于hrHPV血清学检测和将来的检测。 生物标志物检测我们建议有效利用储存的血清，每月hrHPV基因分型结果， hrHPV血清学结果，以评价维生素D水平与HPV感染的存在、持续和再激活的关系。 hrHPV感染。为了探索维生素D参与的不同潜在机制，将对血清进行检测， 几种不同的生物标志物：25-羟基维生素D（25（OH）D）和几种可能更好的替代措施 表征维生素D充足性，包括1，25-二羟基维生素D（1，25（OH）2D）、游离维生素D，以及 生物可利用的维生素D我们的目的是：1）评估血清维生素D与糖尿病之间的横向联系。 水平和普遍hrHPV感染; 2）评估血清维生素D水平和持续性HRHPV感染之间的关联 vs.一过性型特异性hrHPV感染;和3）在基线时有既往hrHPV感染证据的女性中 （血清学阳性/DNA阴性），评估血清维生素D水平与随后的 相同hrHPV类型的再活化。我们推测，血清维生素D水平越高， 与普遍、持续和再活化的hrHPV感染相关。收集到的信息将帮助我们 了解血清维生素D水平是否会影响中年女性的hrHPV自然史。最后， 这些试点数据将是至关重要的，在发展未来的纵向研究，旨在评估是否 达到或维持足够的血清维生素D水平可以积极改变自然史， hrHPV感染。

PROJECT DESCRIPTION Co-factors linked to high-risk (hr) HPV persistence versus transience are not well-defined. Deficiencies in nutrients such as vitamin D can increase the risk of carcinogenesis via DNA damage, immune incompetence, and genetic alterations. While a recent study reported that vitamin D deficiency was associated with an increased likelihood of prevalent hrHPV infection, to our knowledge, no study has explored associations between vitamin D levels and hrHPV persistence or reactivation. From 2011-2012, we recruited 409 healthy mid-adult women to participate in a 6-month longitudinal study of hrHPV infections. Each month, women self- collected vaginal samples for PCR-based genotype-specific hrHPV DNA testing and completed health and sexual behavior questionnaires. In addition, sera were collected for hrHPV serology testing and future biomarker testing. We propose to make efficient use of stored sera, monthly hrHPV genotyping results, and hrHPV serology results to evaluate vitamin D levels in relation to presence, persistence, and reactivation of hrHPV infection. To explore different potential mechanisms of vitamin D involvement, sera will be tested for several different biomarkers: 25-hydroxyvitamin D (25(OH)D) and several alternative measures that may better characterize vitamin D sufficiency, including 1,25-dihydroxyvitamin D (1,25(OH)2D), free vitamin D, and bioavailable vitamin D. Our aims are to: 1) Evaluate cross-sectional associations between serum vitamin D levels and prevalent hrHPV infection; 2) Evaluate associations between serum vitamin D levels and persistent vs. transient type-specific hrHPV infection; and 3) In women with evidence of prior hrHPV infection at baseline (positive serology / negative DNA), evaluate the association between serum vitamin D levels and subsequent reactivation of the same hrHPV type. We hypothesize that higher serum vitamin D levels will be inversely associated with prevalent, persistent, and reactivated hrHPV infection. Information gleaned will help us to understand whether serum vitamin D levels impact the hrHPV natural history in mid-adult women. Ultimately, these pilot data will be crucial in developing future longitudinal studies designed to evaluate whether achievement or maintenance of sufficient serum vitamin D levels can positively alter the natural history of hrHPV infections.