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

项目说明 与高危(Hr)HPV持久性和暂时性相关的辅助因素并没有明确的定义。的不足之处 维生素D等营养素可通过DNA损伤、免疫功能低下、 和基因改变。而最近的一项研究报告称，维生素D缺乏与 据我们所知，hrHPV感染流行的可能性增加，还没有研究探索两者之间的联系 维生素D水平与hrHPV持续或重新激活之间的关系。从2011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，女性都会自我 采集阴道样本进行基于聚合酶链式反应的基因特异性hrHPV DNA检测，并完成健康和 性行为问卷。此外，还收集了用于hrHPV血清学测试和将来的血清 生物标记物检测。我们建议有效利用储存的血清、每月的hrHPV基因分型结果，以及 HrHPV血清学结果评估维生素D水平与存在、持续和重新激活 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 确定维生素D的充分性，包括1，25-二羟基维生素D(1，25(OH)2D)、游离维生素D和 生物可利用维生素D我们的目标是：1)评估血清维生素D的横断面相关性 水平与hrHPV感染的流行；2)评估血清维生素D水平与持续性 与一过性类型特异性hrHPV感染的对比；3)在基线水平有hrHPV感染证据的女性 (血清学阳性/DNA阴性)，评估血清维生素D水平与随后 重新激活相同类型的hrHPV。我们假设较高的血清维生素D水平将是相反的 与流行的、持续的和重新激活的hrHPV感染有关。收集到的信息将帮助我们 了解血清维生素D水平是否影响中年女性的hrHPV自然病史。最终， 这些先导数据将对开发未来的纵向研究至关重要，这些研究旨在评估 达到或维持足够的血清维生素D水平可以积极改变糖尿病的自然病程 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.