HPV DNA负荷量、辅助性T细胞17、FoxP3+调节性T细胞及炎症因子与高危型HPV感染的相关性分析

Correlation analysis of HPV DNA load,helper T cell 17,FoxP3+regulatory T cells and inflammatory factors with high-risk HPV cervical infection

目的探讨人乳头瘤病毒(HPV)DNA、辅助性T细胞17(Th17)、叉头状转录因子3阳性(FoxP3^(+))调节性T细胞(Treg)及宫颈灌洗液中炎症因子与高危型HPV感染的相关性,为高危型HPV感染防治提供新思路。方法将2020年9月至2021年2月该院收治的高危型HPV感染患者100例纳入研究作为研究组,然后将其中50例高危型HPV16/18阳性患者作为HPV16/18组,50例其他12种高危型阳性病例作为其他亚型组。另外,选取同期体检的健康女性作为对照组(n=50)。比较研究组和对照组HPV DNA负荷量、Th17、FoxP3^(+)Treg及宫颈灌洗液中炎症因子[白细胞介素(IL)-10、肿瘤坏死因子α(TNF-α)、IL-17A]水平,比较HPV16/18组和其他亚型组各项指标水平,比较不同宫颈病变患者各项指标水平。分析各项指标与高危型HPV感染、宫颈病变的相关性,以及对宫颈病变患者高危型HPV感染的诊断价值。结果研究组HPV DNA负荷量、Th17、FoxP3^(+)Treg及宫颈灌洗液中IL-10、TNF-α、IL-17A水平均高于对照组(P<0.05),HPV16/18组各项指标水平均高于其他亚型组(P<0.05)。不同宫颈病变患者各项指标水平比较,差异有统计学意义(P<0.05)。HPV DNA负荷量、FoxP3^(+)Treg、Th17及宫颈灌洗液中IL-10、TNF-α、IL-17A水平与高危型HPV感染分型(HPV16/18=1,其他亚型=2)均呈负相关(P<0.05),与宫颈病变(宫颈上皮内瘤变Ⅰ级=1,宫颈上皮内瘤变Ⅱ级=2,宫颈上皮内瘤变Ⅲ级=3,宫颈癌=4)均呈正相关(P<0.05)。各项指标联合诊断高危型HPV16/18阳性的曲线下面积(AUC)为0.911(95%CI:0.837~0.959),大于各指标单独诊断。结论高危型HPV感染患者HPV DNA负荷量、Th17、FoxP3^(+)Treg及炎症因子水平异常,与高危型HPV感染分型、宫颈病变密切相关,而且HPV DNA负荷量与Th17、FoxP3^(+)Treg、炎症因子相关,各项指标联合检测可为临床防治高危型HPV持续感染提供可靠依据。

Objective To investigate the correlation of human papillomavirus(HPV)DNA,T helper cell 17(Th17),forkhead transcription factor 3 pisitive(FoxP3^(+))regulatory T cells(Treg)and inflammatory factors in cervical lavage fluid with high-risk HPV infection,and to provide new ideas for the prevention and treatment of high-risk HPV infection.Methods A total of 100 patients with high-risk HPV infection admitted to the hospital from September 2020 to February 2021 were enrolled in the study as the study group,and then 50 of those patients with high-risk HPV16/18 positive were selected as the HPV16/18 group,and 50 other 12 high-risk HPV positive cases were selected as the other subtype group.In addition,healthy women who underwent physical examination during the same period were enrolled as the control group(n=50).The HPV DNA load,Th17,FoxP3^(+)Treg and inflammatory factors[interleukin(IL)-10,tumor necrosis factorα(TNF-α),IL-17A]in cervical lavage fluid were compared between the study group and the control group,and the levels of the indicators between HPV16/18 group and other subtypes group were compared.The levels of the indicators in patients with different cervical lesions were compared.The correlation between the indicators and high-risk HPV infection,cervical lesions,and their diagnostic value for high-risk HPV infection in patients with cervical lesions were analyzed.Results The HPV DNA load,Th17,FoxP3^(+)Treg and the levels of IL-10,TNF-αand IL-17A in cervical lavage fluid in the study group were higher than those in the control group(P<0.05),and the levels of the indicators in the HPV16/18 group were higher than those in the other subtypes(P<0.05).There were statistically significant differences in the levels of the indicators in patients with different cervical lesions(P<0.05).HPV DNA load,FoxP3^(+)Treg,Th17 and the levels of IL-10,TNF-αand IL-17A in cervical lavage fluid were negatively correlated with high-risk HPV infection type(HPV16/18=1,other subtypes=2,P<0.05),and cervical lesions(cervical intraepithelial neoplasia gradeⅠ=1,cervical intraepithelial neoplasia gradeⅡ=2,cervical intraepithelial neoplasia gradeⅢ=3,cervical cancer=4)were positively correlated(P<0.05).The area under curve(AUC)of the combined detection of the indicators in the diagnosis of high-risk HPV16/18 infection was 0.911(95%CI:0.837—0.959),which was greater than those of the indicators detected alone.Conclusion HPV DNA load,Th17,FoxP3^(+)Treg and inflammatory factors are abnormal in patients with high-risk HPV infection,which are closely related to high-risk HPV infection classification and cervical lesions.Moreover,HPV DNA load is related to Th17,FoxP3^(+)Treg and inflammatory factors.The combined detection of the indicators can provide a reliable basis for the clinical prevention and treatment of high-risk HPV persistent infection.