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目的 探究持续性高危型人乳头瘤病毒(high-risk human papillomavirus, HR-HPV)感染患者血清25-羟维生素D3[25-hydroxyvitamin D3, 25-(OH)D3]、宫颈p16蛋白表达及T辅助细胞(T helper, Th)1/Th2比值的变化及临床意义。方法 选择2021年10月至2022年9月秦皇岛市第一医院收治的108例HR-HPV感染患者为研究对象，根据HPV感染转归分为持续性感染组(n=62)与一过性感染组(n=46)；另选取同期在我院健康体检的50例女性为健康对照组。比较各组基线资料、血清25-(OH)D3、宫颈p16蛋白和Th1/Th2比值，采用Spearman秩相关分析3项指标与子宫颈上皮不典型增生(cervical intraepithelial neoplasia, CIN)分级的相关性，采用多因素Logistic回归筛选持续HR-HPV感染的独立影响因素，采用受试者工作特征(receiver operating characteristic, ROC)曲线分析3项指标单独及联合检测对持续性HR-HPV感染的评估价值。结果 3组在文化程度、初次性生活年龄、性生活频率、性伴侣数量、流产史及避孕套使用情况方面比较，差异均具有统计学意义(均P<0.05)；持续性感染组和一过性感染组在性伴侣数量、CIN Ⅰ级、CINⅢ级及HPV感染分型比较，差异均具有统计学意义(均P<0.05)。血清25-(OH)D3水平、Th1/Th2比值表现为持续性感染组<一过性感染组<健康对照组，而宫颈p16蛋白阳性表达率表现为持续性感染组>一过性感染组>健康对照组(均P<0.05)。Spearman相关性分析显示，持续性感染组患者血清25-(OH)D3水平和Th1/Th2比值与CIN分级呈负相关(P<0.05)，宫颈p16蛋白表达水平与CIN分级呈显著正相关(P<0.05)。多因素Logistic回归分析结果显示，25-(OH)D3、宫颈p16蛋白、Th1/Th2比值、性伴侣个数、CIN分级和HPV感染分型是持续性HR-HPV感染的独立影响因素(P<0.05)。ROC曲线分析结果显示，25-(OH)D3、宫颈p16蛋白和Th1/Th2比值单项检测评估持续性HR-HPV感染的ROC曲线下面积(area under the ROC curve,AUC)分别为0.803、0.716和0.751，敏感度分别为83.87%、75.81%和85.48%，特异度分别为77.72%、70.97%和72.58%,3项指标联合评估AUC为0.864，敏感度为95.16%，特异度为69.35%。结论 持续性HR-HPV感染发生与血清25-(OH)D3、宫颈p16蛋白表达及Th1/Th2比值的变化具有一定关联性，这3项指标或可作为辅助评估及风险分层的潜在参考指标。联合检测可提高敏感度和总体区分效能，但特异度相对降低，临床应用需结合HPV分型、细胞学及阴道镜结果综合判断。
Abstract：Objective To investigate the changes in serum 25-(OH)D3 levels, cervical p16 protein expression, and the T helper 1/T helper 2(Th1/Th2) ratio in patients with persistent high-risk human papillomavirus(HR-HPV) infection. Methods A total of 108 patients with HR-HPV infection admitted to the First Hospital of Qinhuangdao from October 2021 to September 2022 were selected as the study subjects. According to the HPV infection outcomes, the above patients were divided into persistent infection group(n=62) and transient infection group(n=46), and 50 healthy women who underwent health examinations at our hospital during the same period were included in healthy control group. The baseline data, serum 25-(OH)D3, p16 protein and Th1/Th2 ratio were compared among the groups. The correlations between the three indicators and CIN grading were explored by Spearman rank correlation analysis. Multivariate logistic regression analysis was used to identify the independent factors influencing persistent HR-HPV infection. Receiver operating characteristic(ROC) curve was adopted to analyze the evaluation value of the three indicators alone and in combination on persistent HR-HPV infection. Results There were statistically significant differences in education level, age at first sexual intercourse, frequency of sexual activity, number of sexual partners, abortion history, condom use status and pathological classification among the three groups(P<0.05). Statistical differences were found in the number of sexual partners, CIN grade I, CIN grade III and HPV infection type between persistent infection group and transient infection group(P<0.05). Serum 25-(OH) D3 level and Th1/Th2 ratio were lowest in the persistent infection group, intermediate in the transient infection group, and highest in the healthy control group, while the positive expression rate of p16 protein revealed the opposite trend(P<0.05). Spearman correlation analysis indicated that serum 25-(OH)D3 and Th1/Th2 ratio in persistent infection group were negatively correlated with CIN grading(P<0.05), and p16 protein expression was positively correlated with CIN grading(P<0.05). Multivariate logistic regression analysis demonstrated that 25-(OH)D3, p16 protein, Th1/Th2 ratio, number of sexual partners, CIN grading and HPV infection type were independent factors affecting persistent HR-HPV infection(P<0.05). ROC curve analysis revealed that the areas under the ROC curves of 25-(OH)D3, p16 protein and Th1/Th2 ratio in evaluating persistent HR-HPV infection were 0.803, 0.716 and 0.751, and the sensitivities were 83.87%, 75.81% and 85.48%, and the specificities were 77.72%, 70.97% and 72.58% respectively. The AUC, sensitivity and specificity of combined evaluation with the three indicators were 0.864, 95.16% and 69.35%. Conclusion The occurrence of persistent HR-HPV infection is related to the changes of serum 25-(OH)D3, p16 protein and Th1/Th2 ratio. These 3 indicators may serve as potential biological biomarkers for the clinical screening and assessment of persistent HR-HPV infection, and combined assessment showed better overall discriminative performance.
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基本信息:
中图分类号:R737.33;R711
引用信息:
[1]李秀福,姜丽,龚姗,等.持续性HR-HPV感染患者血清25-(OH)D_3、宫颈P16蛋白及Th1/Th2比值的变化及其相关性分析[J].传染病信息,2026,39(04):346-352.
基金信息:
河北省2022年度医学科学研究项目（20221606）
2026-08-30
2026-08-30