阴道灌洗液中炎症因子与CD4+和CD8+T细胞在高级别宫颈鳞状上皮内病变与早期宫颈癌发病中的作用研究

Study on the effect of inflammatory factors and CD4+ and CD8+T cells in vaginal lavage in high-grade cervical squamous intraepithelial lesions and early cervical cancer

  • 摘要:
    目的 探讨阴道灌洗液中CD4+与CD8+T细胞亚群分布及局部炎症因子水平在高级别宫颈鳞状上皮内病变(high-grade cervical squamous intraepithelial lesions,HSIL)与早期宫颈鳞癌发病中的作用。
    方法 收集桂林市人民医院高危型人类乳头状瘤病毒(high-risk human papilloma virus,HR-HPV)感染的HSIL患者120例和早期宫颈癌(cervical cancer,CC)患者144例的临床资料。并随机选取未感染HR-HPV的健康女性60例作为对照组。比较3组患者的临床资料、血清和宫颈灌洗液炎症因子(IL-2、INF-γ、IL-10、TNF-α)、CD4+与CD8+T细胞分布与比值。多因素逻辑回归分析HSIL进展至早期CC的影响因素,绘制ROC及校准图对模型评估。
    结果 对照组、HSIL组与早期CC组患者血IL-2、INF-γ、IL-10、TNF-α水平、CD4+细胞分布、CD8+T细胞分布与CD4+/CD8+比值比较,差异均无统计学意义(均P>0.05);3组患者阴道灌洗液中IL-2、INF-γ、IL-10、TNF-α水平、CD4+细胞分布、CD8+T细胞分布与CD4+/CD8+比值比较,差异均具有统计学意义(均P<0.05),且早期CC组高于HSIL组及对照组(均P<0.05),HSIL组高于对照组(P<0.05)。逻辑回归分析显示,模型2中产次>2次(OR=3.119,95%CI:4.353~6.737)与阴道灌洗液CD4+T细胞百分比(OR=0.327,95%CI:0.188~0.478)(P<0.001,AUC=0.908),模型3中CD4+/CD8+(OR=0.809,95%CI:0.356~1.868)(P<0.001,AUC=0.873)对HSIL发展至早期CC有独立影响;两模型ROC曲线无明显差异(Z=1.5504,P=0.121)。模型3中仅用CD4+/CD8+就能良好预测,该模型为优,该模型校准曲线与标准曲线接近。
    结论 HR-HPV感染后,宫颈局部免疫状态参与HSIL及HSIL进展至早期CC,且CD4+/CD8+T细胞比值可作为其独立保护因素。

     

    Abstract:
    Objective To investigate the effect of inflammatory factors (IL-2, INF-γ, IL-10, TNF-α) and CD4+ and CD8+T cells in vaginal lavage in high-grade cervical squamous intraepithelial lesions (HSIL) and early cervical cancer (CC).
    Methods To collect clinical data of HSIL (n=120) and early CC patients (n=44) after high-risk human papilloma virus (HR-HPV) infection. And healthy middle-aged women not infected with HR-HPV were randomly selected as control. The clinical data of the subjects in three groups were compared, inflammatory factors distribution and ratio of CD4+ and CD8+T cells in serum and vaginal lavage fluid were compared. Multivariate Logistic regression performed to analyze the influencing factors of HSIL progression to early CC, ROC and calibration plot were drawn to evaluate the model.
    Results The difference was not statistically significant in serum IL-2, INF-γ, IL-10, TNF-α levels, CD4+T cell distribution, CD8+T cell distribution and CD4+/CD8+ ratio in subjects of control group, HSIL group and early CC group (P>0.05). The difference was statistically significant in the vaginal lavage levels of IL-2, INF-γ, IL-10, TNF-α levels, CD4+T cell distribution, CD8+T cell distribution and CD4+/CD8+ ratio (P<0.05), plus the level of HSIL patients was higher than that of control subjects (P<0.05). Logistic regression analysis showed that parity >2 (OR=3.119, 95%CI: 4.353~6.737) and the percentage of CD4+T cells in vaginal lavage fluid (OR=0.327, 95%CI: 0.188-0.478) in model 2 (P<0.001, AUC=0.908), CD4+/CD8+(OR=0.809, 95%CI: 0.356-1.868) (P<0.001, AUC=0.873) in model 3 has an independent influence on the development of HSIL to early CC; the difference is not significant (Z=1.5504, P=0.121) in ROC curves of the two models. CD4+/CD8+ ratio as only one indictor in Model 3 can be good prediction, and the calibration curve of this model is close to the standard curve.
    Conclusions After HR-HPV infection, the systemic immune status does not participate in HSIL and HSIL progression to early CC, but the cervical local immune status is involved, in which CD4+/CD8+T cell ratio is an independent protective factor.

     

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