高危型人乳头瘤病毒感染的不同级别子宫颈病变患者细胞免疫状态分析

Analysis of cellular immune status in patients with different grades of cervical lesions infected with high-risk human papillomavirus(HR-HPV)

目的探索高危型人乳头瘤病毒(HR-HPV)感染的不同级别子宫颈病变患者外周血T淋巴细胞亚群的表达情况及意义。方法选取2020年12月至2021年10月于北京大学人民医院拟行子宫颈锥切手术的194例子宫颈高级别鳞状上皮内病变(HSIL)患者(子宫颈HSIL组)、30例子宫颈癌患者(子宫颈癌组)和同期病房的230例子宫颈低级别鳞状上皮内病变(LSIL)患者及子宫颈息肉、子宫内膜息肉患者(对照组)。用流式细胞仪检测各组患者外周血的NK细胞、B细胞、CD8^(+)T细胞、CD4^(+)T细胞、总T细胞、总淋巴细胞计数及CD4^(+)T细胞计数与CD8^(+)T细胞计数的比值(CD4^(+)/CD8^(+))并进行比较。结果子宫颈HSIL组及子宫颈癌组HR-HPV阳性率达95.9%。对照组、子宫颈HSIL组、子宫颈癌组患者外周血NK细胞逐渐升高,差异具有统计学意义(P=0.012)。HR-HPV阳性患者外周血中NK细胞计数及总淋巴细胞计数比HR-HPV阴性者高,差异具有统计学意义(P值分别为0.007和0.036)。亚组分析中,在HR-HPV感染而未出现HSIL及以上子宫颈病变时,淋巴细胞亚群未见显著改变。而HPV16/18持续性感染相关的HSIL或子宫颈癌,患者CD8^(+)T细胞、总淋巴细胞计数显著高于HPV阴性的HSIL或子宫颈癌患者,且CD4^(+)T细胞、T总淋巴细胞计数有升高趋势,但差异无统计学意义。结论HR-HPV感染是子宫颈HSIL及子宫颈癌的高危因素,与外周血NK细胞及总淋巴细胞计数升高有关。HPV 16/18感染相关的HSIL及以上病变,CD8^(+)T细胞计数显著升高。HPV高危型感染与淋巴细胞亚群变化关系密切。

Objective To explore the expression and significance of T lymphocyte subsets in peripheral blood of patients with different grades of cervical lesions infected with high-risk human papillomavirus(HPV).Methods Totally 194 cases of high-grade cervical intraepithelial neoplasia(HSIL)and 30 cases of cervical cancer who were scheduled to undergo cervical conization in Peking University People's Hospital from December 2020 to October 2021 were selected as the case group.Totally 230 cases of CIN1 patients,cervical polyps and endometrial polyps in the same ward were selected as the control group.Flow cytometry was used to detect and compare NK cells,B cells,CD8^(+),CD4^(+),CD4/CD8^(+),total T cells and total lymphocytes in peripheral blood of patients with different levels of cervical lesions.ResultsThe positive rate of HPV high-risk type in cervical HSIL group and cervical cancer group was 95.9%.NK cells in lymphocytes of the control group,cervical HSIL group&cervical cancer group increased gradually,with significant differences(the P-values is 0.012).NK and total lymphocytes in peripheral blood of HPV high-risk positive patients were significantly higher than those of HPV negative patients(the P-values are 0.007 and 0.036,respectively).In subgroup analysis,when HPV high-risk infection did not cause HSIL or above cervical lesions,there was no significant difference in lymphocyte subsets.When HPV16/18+persistent infection causes HSIL or cervical cancer,the indexes of CD8^(+)and total lymphocytes of patients were significantly higher than those of HPV negative cervical HSIL or cervical cancer patients,while the indexes of CD4^(+)and total T lymphocytes had an upward trend,but the difference was not significant.Conclusions HR-HPV infection is a high risk factor for cervical in traepithelial neoplasia and cervical cancer,which may cause NK cells and total lymphocytes in peripheral lymphocytes to increase.When HPV 16/18 infection causes HSIL and above lesions,CD8^(+)T cells increase significantly.High-risk HPV infection is closely related to the change of lymphocyte subsets.