宫颈癌手术清除HPV效果及Th17/Treg细胞变化

Effect of cervical cancer surgery on eradication of HPV and change of Th17/Treg cells

目的分析宫颈癌(cervical carcinoma,CC)手术对人乳头瘤病毒(Human Papilloma Virus,HPV)感染和外周血辅助性T细胞17(T Helper cell 17,Th17)、调节性T细胞(Regular T cell, Treg)及炎症因子的影响,为评价和优化手术治疗效果提供依据。方法选取2016年10月-2019年10月于海口市妇幼保健院住院的40例HPV阳性早期CC患者作为研究组,选取同期40例HPV阳性宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)Ⅱ~Ⅲ级患者作为对照组,对两组患者术后宫颈HPV检测情况进行分析;对两组患者手术前、后血清白细胞介素(Interleukin,IL)-6、IL-17、IL-23、转化生长因子-β(Transforming Growth Factor-β,TGF-β)、IL-10水平进行检测和对比;对两组患者手术前、后外周血CD_(4)^(+)CD_(25)^(+)Treg细胞比例、CD_(4)^(+)CD_(17)^(+)Th17细胞比例、Th17/Treg细胞比值进行检测和对比。结果研究组和对照组术后分别有25例、20例患者术后宫颈HPV检测由阳性转为阴性,两组HPV转阴率比较差异无统计学意义;研究组患者术前血清TGF-β、IL-6、IL-23水平高于对照组,外周血CD_(4)^(+)CD_(25)^(+)Treg细胞比例、CD_(4)^(+)CD_(17)^(+)Th17细胞比例、Th17/Treg细胞比值均高于对照组,术后1个月,两组患者的上述指标均较术前下降,研究组患者血清TGF-β、IL-6、IL-23水平的降低幅度高于对照组,外周血CD_(4)^(+)CD_(17)^(+)Th17细胞比例、Th17/Treg细胞比值的降低幅度高于对照组,差异均有统计学意义(P<0.05);术后1个月,宫颈HPV检测阳性CC患者的外周血CD_(4)^(+)CD_(25)^(+)Treg细胞比例、CD_(4)^(+)CD_(17)^(+)Th17细胞比例、Th17/Treg细胞比值均高于宫颈HPV检测阴性CC患者,差异均有统计学意义(P<0.05)。结论 CC及癌前病变患者均存在着Th17/Treg细胞功能失衡,且CC患者更加严重,手术治疗能够有效纠正此种免疫失衡状态,但术后HPV阳性患者的Th17/Treg细胞功能失衡程度仍高于HPV转阴患者,临床医生应重视复查术后宫颈HPV、充分评价术后免疫炎症状态,从而预测复发风险。

OBJECTIVE To observe the influence of cervical carcinoma(CC)surgery on human papilloma virus(HPV)infections,peripheral blood T helper cell 17(Th17)/T regulatory cell(Treg)and inflammatory factors so as to provide guidance for evaluation and optimization of effects of surgical treatment.METHODS Totally 40 early CC patients who were positive for HPV and hospitalized in Haikou Maternal and Child Health Care Hospital from Oct 2016 to Oct 2019 were assigned as the study group,meanwhile,40 HPV-positive patients with grageⅡ-Ⅲcervical intraepithelial neoplasia(CIN)were set as the control group.The status of detection of HPV in cervical secretions of the two groups of patients was analyzed after the surgery,the levels of serum interleukin(IL)-6,IL-17,IL-23,transforming growth factor-β(TGF--β)and IL-10 were compared between the two groups of patients before and after the surgery,the percentage of peripheral blood CD_(4)^(+)CD_(25)^(+)Treg cells,percentage of CD_(4)^(+)CD17+Th17 cells and ratio of Th17/Treg were compared between the two groups of patients before and after the surgery.RESULTS There were 25 cases with postoperative cervical HPV tested from positive to negative in the study group and 20 cases in the control group,and there was no significant difference in the negative rate of HPV between the two groups.The levels of preoperative serum TGF-β,IL-6 and IL-23 of the study group were higher than those of the control group;the percentage of peripheral blood CD_(4)^(+)CD_(25)^(+)Treg cells,percentage of CD_(4)^(+)CD17+Th17 cells and Th17/Treg ratio of the study group were higher than those of the control group;the levels of above indexes of the two groups of patients were reduced after the surgery for 1 month;the levels of serum TGF-β,IL-6 and IL-23 were reduced more significantly in the study group than in the control group,the percentage of peripheral blood CD_(4)^(+)CD17+Th17 cells and Th17/Treg ratio were reduced more significantly in the study group than in the control group(P<0.05).The percentage of peripheral blood CD_(4)^(+)CD_(25)^(+)Treg cells,percentage of CD_(4)^(+)CD17+Th17 cells and Th17/Treg ratio of the cervical HPV-positive CC patients were significantly higher than those of the cervical HPV-negative CC patients after the surgery for 1 month(P<0.05).CONCLUSION The CC and precancerous lesions patients have the imbalance of Th17/Treg cell function,which is more severe in the CC patients,the surgical procedures can effectively rectify the immune imbalance,however,the imbalance of Th17/Treg cell function of the HPV-positive patients is more severe than that of the HPV-negative patients after the surgery,and it is necessary for clinicians to attach great importance to reexamination of postoperative cervical HPV and evaluation of postoperative immune inflammation state so as to predict the risk of recurrence.