Circulating biomarkers of iron storage and clearance of incident human papillomavirus infection.
Circulating biomarkers of iron storage and clearance of incident human papillomavirus infection.
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铁储存和清除人乳头瘤病毒感染事件的循环生物标志物。
DOI：
10.1158/1055-9965.epi-12-0073
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Giuliano,AnnaR
中科院分区：
文献类型：
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作者：
Siegel,ErinM;Patel,Nitin;Lu,Beibei;Lee,Ji-Hyun;Nyitray,AlanG;Huang,Xi;Villa,LuisaL;Franco,EduardoL;Giuliano,AnnaR
背景：铁是细胞和病原体生存的必需矿物质，也是病毒复制所必需的。反过来，铁代谢已被证明会因几种病毒感染而改变。然而，人们对铁状态与人乳头瘤病毒（HPV）自然史之间的关系知之甚少。我们假设铁是一种 HPV 辅助因子，与较长的感染持续时间相关。方法：对 Ludwig-McGill 队列中 327 名女性的基线血清样本中的铁蛋白和可溶性转铁蛋白受体 (sTfR) 进行测量。根据考虑多种感染之间相关性的 Cox 比例风险模型估计了 3 年期间的事件 HPV 清除率（任何类型、致癌 HPV、非致癌 HPV 和 HPV-16）。结果：铁蛋白水平高于中位数的女性清除事件致癌 HPV 的可能性较小[调整后风险比 (AHR)，0.73； 95% 置信区间 (CI)，0.55–0.96] 和 HPV-16 感染（AHR，0.29；95% CI，0.11–0.73）。使用生理临界点，与铁含量低（<20 μg/L；AHR，0.34；95% CI，0.15–0.81）的女性相比，铁储备丰富（>120 μg/L）的女性清除致癌 HPV 感染的可能性较小。结论：本研究观察到，铁蛋白水平最高的女性清除致癌和 HPV-16 感染的可能性较小。 感染率高于铁蛋白水平低的女性。铁储存量增加可能会降低清除新 HPV 感染的可能性，这可能是通过促进病毒活性和氧化 DNA 损伤造成的。影响：这项新研究表明，铁储存量增加可能会使女性面临持续 HPV 感染的风险，这是宫颈癌发生的早期事件。有必要进一步检查铁状态与 HPV 自然史之间的关联。 21(5)； 859–65。 ©2012 AACR。
Background:Iron is an essential mineral for both cellular and pathogen survival and is essential for viral replication. In turn, iron metabolism has been shown to be altered by several viral infections. However, little is known about the association between iron status and human papillomavirus (HPV) natural history. We hypothesize iron to be an HPV cofactor that is associated with longer duration of infection.Methods:Ferritin and soluble transferrin receptor (sTfR) were measured in baseline serum samples from 327 women enrolled in the Ludwig–McGill cohort. Incident HPV clearance rates (any-type, oncogenic HPV, nononcogenic HPV, and HPV-16) over a 3 year time period were estimated from Cox proportional hazard models accounting for correlations between multiple infections.Results:Women with ferritin levels above the median were less likely to clear incident oncogenic HPV [adjusted hazard ratio (AHR), 0.73; 95% confidence interval (CI), 0.55–0.96] and HPV-16 infections (AHR, 0.29; 95% CI, 0.11–0.73). Using physiologic cutoff points, women with enriched iron stores (>120 μg/L) were less likely to clear incident oncogenic HPV infections than those with low levels of iron (<20 μg/L; AHR, 0.34; 95% CI, 0.15–0.81).Conclusion:This study observed that women with the highest ferritin levels were less likely to clear incident oncogenic and HPV-16 infections than women with low ferritin. Rising iron stores may decrease probability of clearing new HPV infection, possibly by promoting viral activity and contributing to oxidative DNA damage.Impact:This novel study suggests that elevated iron stores may put women at risk for persistent HPV infection, an early event in cervical carcinogenesis. Further examination of the association between iron status and HPV natural history is warranted.Cancer Epidemiol Biomarkers Prev; 21(5); 859–65. ©2012 AACR.