高危型人乳头状瘤病毒载量和Th1/Th2不均衡表达预测宫颈癌变进程的研究

doi:10.11904/j.issn.1002-3070.2018.06.010

实用肿瘤学杂志 ›› 2018, Vol. 32 ›› Issue (6): 533-537.doi: 10.11904/j.issn.1002-3070.2018.06.010

高危型人乳头状瘤病毒载量和Th1/Th2不均衡表达预测宫颈癌变进程的研究

付艳丽, 余杨, 卫玮, 邹晶晶, 孙翔

河南理工大学第一附属医院(河南省焦作市第二人民医院)检验科(焦作 454100)

收稿日期:2018-04-24 出版日期:2018-12-28 发布日期:2018-12-27
通讯作者: 余杨, E-mail:yy5834lyr@126.com
作者简介:付艳丽, 女, (1970-), 本科, 主管技师, 从事临床免疫学检验和科研工作的研究。
基金资助:
河南省医学科技攻关项目(编号:201702356)

Study on predicting the cervical cancinogenesis by high-risk human papillomavirus load and the unbalanced expression of Th1/Th2

FU Yanli, YU Yang, WEI Wei, ZOU Jingjing, SUN Xiang

Department of Laboratory, The First Affiliated Hospital of Henan Polytechnic University, Jiaozuo Second People's Hospital of Henan Province, Jiaozuo 454100, China

Received:2018-04-24 Online:2018-12-28 Published:2018-12-27

摘要/Abstract

摘要： 目的比较高危型人乳头状瘤病毒载量(HR-HPV DNA)、Th1和Th2型细胞因子在不同宫颈局部微环境的表达差异, 探讨其预测宫颈癌变的可能性和意义。方法将339例HR-HPV持续感染者分为宫颈上皮内瘤变(CIN)和宫颈癌两组, 以HPV阴性且细胞学检查为正常宫颈的40例作为对照, 采用PCR荧光法和双抗体夹心ELISA法分别检测宫颈分泌物HPV-DNA以及Th1型细胞因子:白细胞介素-2(IL-2)、干扰素-γ(IFN-γ)、肿瘤坏死因子-ɑ(TNF-ɑ)和Th2型细胞因子IL-4、IL-6、IL-10的表达水平, 以TNF-ɑ/IL-10比值作为衡量Th1/Th2免疫平衡的指标, 对数据资料进行单因素方差分析和多因素Logistic回归分析, 筛选宫颈癌预测指标。结果单因素方差分析显示, HR-HPV DNA、IL-2、IL-4、IL-6、IL-10、IFN-γ、TNF-ɑ、TNF-ɑ/IL-10在CIN和宫颈癌组均存在统计学差异(P＜0.05), 可以作为预测宫颈癌变的危险因素, 而多因素Logistic回归分析显示, 仅IL-10、IFN-γ、TNF-ɑ、TNF-ɑ/IL-10是宫颈癌发生的影响因素, 回归模型拟合优度检验Nagelkerke R²=0.982, 对CIN的预判率为99.5%, 宫颈癌的预判率为100.0%, 总的正判率为99.7%, 提示拟合效果好, 预测准确度高。结论 CINⅠ和CINⅡ有Th细胞因子的异常表达, 但不影响Th1/Th2平衡, CINⅢ阶段Th1/Th2失衡, Th2优势表达促进宫颈癌发生, 基于预测宫颈癌变的回归模型, 局部免疫失衡造成的宫颈免疫抑制微环境是HR-HPV持续感染和宫颈癌变的关键环节, 与HR-HPV DNA无关。

关键词: 宫颈局部免疫微环境, 宫颈癌变, Th1/Th2细胞因子, 高危型人乳头状瘤病毒载量, 预测模型

Abstract: Objective The aims of this study were to compare the different expression between high-risk human papillomavirus load(HR-HPV DNA)and Th1/Th2 type cytokines in local different microenvironments of cervix, and to explore the possibility and significance of predicting cervical cancer. Methods A total of 339 patients with persistent HR-HPV infection were divided into cervical intraepithelial neoplasia(CIN)and cervical cancer.Forty patients with HPV-negative and cytological examination of normal cervix were used as controls.PCR fluorescence assay and double antibody sandwich were used.ELISA assay were used to detect HPV-DNA and Th1 type cytokines including IL-2, IFN-γ, TNF-ɑ and Th2 type cytokines including IL-4, IL-6 and IL-10 from cervical secretion.The ratio of TNF-ɑ/IL-10 was used as an index to measure the immune balance of Th1/Th2.Univariate and multivariate logistic regression were performed to analyze the data and then to screen the predicting indicators of cervical cancer. Results Univariate analysis showed that HR-HPV DNA, IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-ɑ and TNF-ɑ/IL-10 were significantly different between CIN and cervical cancer groups(P＜0.05), which could be used as a risk factor for predicting cervical cancer.Multivariate logistic regression analysis showed that IL-10, IFN-γ, TNF-ɑ, TNF-ɑ/IL-10 were the influencing factors of cervical cancer.The regression model fitted goodness test was Nagelkerke(R²= 0.982), the pre-judgment rate for CIN was 99.5%, the pre-judgment rate of cervical cancer was 100%, and the total positive rate was 99.7%, suggesting good fitting effect was good and the prediction accuracy was high. Conclusion CINⅠ and CINⅡ have abnormal expression of Th cytokine, but they do not affect Th1/Th2 balance.Th1/Th2 imbalance in CINⅢ stage and Th2 dominant expression promote the occurrence of cervical cancer.Based on the regression model for predicting cervical carcinogenesis, cervical immunity caused inhibitory microenvironment by local immune imbalance is the key link in HR-HPV persistent infection and cervical cancer, and has nothing to do with HR-HPV DNA.

Key words: Local immune microenvironment of cervix, Cervical carcinogenesis, Th1/Th2 type cytokines, High risk human papillomavirus load, Prediction model

中图分类号:

R446.6

付艳丽, 余杨, 卫玮, 邹晶晶, 孙翔. 高危型人乳头状瘤病毒载量和Th1/Th2不均衡表达预测宫颈癌变进程的研究[J]. 实用肿瘤学杂志, 2018, 32(6): 533-537.

FU Yanli, YU Yang, WEI Wei, ZOU Jingjing, SUN Xiang. Study on predicting the cervical cancinogenesis by high-risk human papillomavirus load and the unbalanced expression of Th1/Th2[J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(6): 533-537.

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高危型人乳头状瘤病毒载量和Th1/Th2不均衡表达预测宫颈癌变进程的研究

Study on predicting the cervical cancinogenesis by high-risk human papillomavirus load and the unbalanced expression of Th1/Th2

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