HPV感染对宫颈免疫微环境的影响
|
摘要
目的比较高危型和低危型人乳头瘤病毒(HPV)感染后宫颈局部细胞因子和阴道微生态指标变化情况,分析不同HPV感染对宫颈局部免疫微环境的影响。方法收集2017年3月～2018年7月在湖南医药学院第一附属医院门诊就诊的妇女宫颈和阴道分泌物标本,用PCR-反向点杂交法检测HPV,根据检测结果将155例标本分为高危型HPV组(55例)、低危型HPV组(40例)和未感染HPV的对照组(60例),用酶联免疫吸附试验测定宫颈细胞保存液中的γ干扰素(IFN-γ)、白细胞介素4(IL-4)和IL-21含量,并按全国临床检验操作规程做真菌、阴道滴虫、线索细胞、清洁度和pH检查。结果与对照组和低危型HPV组比较,高危型HPV组的IFN-γ和IL-21含量均显著降低(P <0.01),但IL-4含量显著升高(P <0.01);与对照组比较,低危型HPV组的IFN-γ含量显著降低(P <0.01),但IL-4和IL-21含量比较,差异无统计学意义(P> 0.05)。经相关性分析,高危型HPV组、低危型HPV组和对照组的IL-21与IFN-γ含量均呈正相关(r=0.74,P <0.01;r=0.70,P <0.01;r=0.66,P <0.01),高危型和低危型HPV组的IL-4与IFN-γ含量均呈负相关(r=-0.33,P <0.05;r=-0.44,P <0.01);高危型HPV组的IL-21与IL-4含量呈负相关(r=-0.30,P <0.05)。此外,三组间真菌、阴道滴虫、线索细胞、清洁度和pH等微生态指标的比较,差异均无统计学意义(P> 0.05)。结论高危型HPV比低危型HPV感染后更易引起宫颈局部IL-4和IFN-γ的表达异常,可能与具有免疫促进作用的IL-21低表达有关。因此,维持宫颈局部正常免疫微环境、恢复机体的免疫调节功能对机体清除HPV、阻断HPV的持续感染非常重要。
Objective To compare the changes of cervical local cytokines and vaginal microecological indicators after the infection of high-risk and low-risk human papillomavirus(HPV), and to analyze the effects of different HPV infections on the cervical local immune microenvironment. Methods Collection in March 2017 to July 2018 in the First Affiliated Hospital of Hu′nan University of Medicine Outpatient Clinic women specimens of cervical and vaginal secretions was carried out, PCR-reverse dot hybridization method was used to detect HPV, according to the results, the 155 cases were divided into high risk type HPV group(55 cases), low-risk HPV group(40 cases) and control group(60 cases), who were not infected with HPV. Cervical cell preservation solution enzyme linked immunosorbent test was carried out in the gamma interferon(IFN-γ), interleukin 4(IL-4) and IL-21 content, and according to the national clinical inspection procedures, the fungi, vaginal trichomoniasis, clue cell, cleanliness, and pH checks were carried out. Results Compared with the control group and low-risk HPV group, the content of IFN-γ and IL-21 in high-risk HPV group was significantly decreased(P < 0.01), but the content of IL-4 was significantly increased(P < 0.01). Compared with the control group, the IFN-γ content of low-risk HPV group was significantly reduced(P < 0.01), but the difference between IL-4 and IL-21 was not statistically significant(P > 0.05). After correlation analysis, IL-21 was positively correlated with IFN-γ content in high-risk HPV group, low-risk HPV group and control group(r = 0.74, P < 0.01), r = 0.70, P <0.01; r = 0.66, P < 0.01), IL-4 and IFN-γ contents in the high-risk and low-risk HPV groups were negatively correlat ed(r =-0.33, P < 0.05; r =-0.44, P < 0.01); IL-21 was negatively correlated with IL-4 in the high-risk HPV group(r =-0.30, P < 0.05). In addition, there were no statistically significant differences among the three groups in microecological indicators such as fungi, vaginal trichomonas, clue cells, cleanliness and pH(P > 0.05). Conclusion High-risk HPV is more likely to cause abnormal expression of local IL-4 and IFN-γ in the cervix after HPV infection than low-risk HPV infection, which may be related tothe low expression of IL-21 with immune-promoting effect. Therefore, it is very important to maintain the local normal immune microenvironment in the cervix and restore the immune regulatory function of the body to remove HPV and block the continuous infection of HPV.
Objective To compare the changes of cervical local cytokines and vaginal microecological indicators after the infection of high-risk and low-risk human papillomavirus(HPV), and to analyze the effects of different HPV infections on the cervical local immune microenvironment. Methods Collection in March 2017 to July 2018 in the First Affiliated Hospital of Hu′nan University of Medicine Outpatient Clinic women specimens of cervical and vaginal secretions was carried out, PCR-reverse dot hybridization method was used to detect HPV, according to the results, the 155 cases were divided into high risk type HPV group(55 cases), low-risk HPV group(40 cases) and control group(60 cases), who were not infected with HPV. Cervical cell preservation solution enzyme linked immunosorbent test was carried out in the gamma interferon(IFN-γ), interleukin 4(IL-4) and IL-21 content, and according to the national clinical inspection procedures, the fungi, vaginal trichomoniasis, clue cell, cleanliness, and pH checks were carried out. Results Compared with the control group and low-risk HPV group, the content of IFN-γ and IL-21 in high-risk HPV group was significantly decreased(P < 0.01), but the content of IL-4 was significantly increased(P < 0.01). Compared with the control group, the IFN-γ content of low-risk HPV group was significantly reduced(P < 0.01), but the difference between IL-4 and IL-21 was not statistically significant(P > 0.05). After correlation analysis, IL-21 was positively correlated with IFN-γ content in high-risk HPV group, low-risk HPV group and control group(r = 0.74, P < 0.01), r = 0.70, P <0.01; r = 0.66, P < 0.01), IL-4 and IFN-γ contents in the high-risk and low-risk HPV groups were negatively correlat ed(r =-0.33, P < 0.05; r =-0.44, P < 0.01); IL-21 was negatively correlated with IL-4 in the high-risk HPV group(r =-0.30, P < 0.05). In addition, there were no statistically significant differences among the three groups in microecological indicators such as fungi, vaginal trichomonas, clue cells, cleanliness and pH(P > 0.05). Conclusion High-risk HPV is more likely to cause abnormal expression of local IL-4 and IFN-γ in the cervix after HPV infection than low-risk HPV infection, which may be related tothe low expression of IL-21 with immune-promoting effect. Therefore, it is very important to maintain the local normal immune microenvironment in the cervix and restore the immune regulatory function of the body to remove HPV and block the continuous infection of HPV.
引文
[1]赵静,陈汶,刘植华,等.常见阴道微生态异常与高危型HPV感染及子宫颈癌相关性研究进展[J].中国热带医学,2018,18(11):1099-1102.
[2]Piersma SJ.Immunosuppressive tumor microenvironment in cervical cancer patients[J].Cancer Microenviron,2011,4(3):361-375.
[3]Barros MR,de Melo CML,Barros MLCMGR,et al.Activities of stromal and immune cells in HPV-related cancers[J].J Exp Clin Cancer Res,2018,37(1):137.
[4]曹建芳,郝敏,赵卫红.宫颈微环境免疫功能与宫颈癌[J].国际妇产科学杂志,2015,42(3):249-252.
[5]尚红,王毓三,申子瑜.全国临床检验操作规程[M].4版.北京:人民卫生出版社,2015:196-197.
[6]Stone SC,Rossetti RA,Lima AM,et al.HPV associated tumor cells control tumor microenvironment and leukocytosis in experimental models[J].Immun Inflamm Dis,2014,2(2):63-75.
[7]Haedicke J,Iftner T.Human papillomaviruses and cancer[J]Radiother Oncol,2013,108(3):397-402.
[8]茹普霞,李东燕.阴道微生态平衡与持续性高危型HPV感染分析[J].山西医科大学学报,2017,48(12):1288-1290.
[9]陶瑞,朱丹,孙鹥,等.人乳头瘤病毒感染与宫颈局部细胞因子相关性研究[J].国际检验医学杂志,2017,38(15):2028-2033.
[10]Xue J,Wang Y,Chen C,et al.Effects of Th17 cells and IL-17 in the progression of cervical carcinogenesis with high-risk human papillomavirus infection[J].Cancer Med,2018,7(2):297-306.
[11]洪慧,王鹤.HPV16、58型感染导致宫颈微环境中免疫因子变化及宫颈细胞中病毒整合的初步研究[J].中国免疫学杂志,2014,30(10):1378-1382.
[12]Feng Q,Wei H,Morihara J,et al.Th2 type inflammation promotes the gradual progression of HPV-infected cervical cells to cervical carcinoma[J].Gynecol Oncol,2012,127(2):412-419.
[13]Hamming OJ,Kang L,Svensson A,et al.Crystal structure of interleukin-21 receptor(IL-21R)bound to IL-21 reveals that sugar chain interacting with WSXWS motif is integral part of IL-21R[J].J Biol Chem,2012,287(12):9454-9460.
[14]Davis MR,Zhu Z,Hansen DM,et al.The role of IL-21 in immunity and cancer[J].Cancer Lett,2015,358(2):107-114.
[15]方丽娟.IL-21在肿瘤免疫治疗中的应用及研究进展[J].国际免疫学杂志,2006,29(3):189-193.
[16]Castro Sobrinho JM,Rabelo Santos SH,Fugueiredo Alves RR,et al.Bacterial vaginosis and inflammatory response showed association with severity of cervical neoplasia in HPV-positive women[J].Diagn Cytopathol,2016,44(2):80-86.
[17]杨少岩,吴潇,李杰,等.阴道微环境改变与宫颈病变的相关性分析[J].中国临床保健杂志,2017,20(3):247-250.
[18]陈忆,吴丹,李柱南,等.细菌性阴道病和阴道微生态改变与高危型人乳头瘤病毒感染的临床分析[J].中国医药导报,2018,15(21):86-89.
[19]Godoy-Vitorino F,Romaguera J,Zhao C,et al.Cervicovaginal Fungi and Bacteria Associated With Cervical Intraepithelial Neoplasia and High-Risk Human Papillomavirus Infections in a Hispanic Population[J].Front Microbiol,2018,23(9):2533.
[20]谢建萍,杨志红,伊芳,等.宫颈高危型人乳头瘤病毒感染与阴道菌群及宫颈局部免疫功能的关系[J].中华医院感染学杂志,2017,27(10):2336-2339.
[2]Piersma SJ.Immunosuppressive tumor microenvironment in cervical cancer patients[J].Cancer Microenviron,2011,4(3):361-375.
[3]Barros MR,de Melo CML,Barros MLCMGR,et al.Activities of stromal and immune cells in HPV-related cancers[J].J Exp Clin Cancer Res,2018,37(1):137.
[4]曹建芳,郝敏,赵卫红.宫颈微环境免疫功能与宫颈癌[J].国际妇产科学杂志,2015,42(3):249-252.
[5]尚红,王毓三,申子瑜.全国临床检验操作规程[M].4版.北京:人民卫生出版社,2015:196-197.
[6]Stone SC,Rossetti RA,Lima AM,et al.HPV associated tumor cells control tumor microenvironment and leukocytosis in experimental models[J].Immun Inflamm Dis,2014,2(2):63-75.
[7]Haedicke J,Iftner T.Human papillomaviruses and cancer[J]Radiother Oncol,2013,108(3):397-402.
[8]茹普霞,李东燕.阴道微生态平衡与持续性高危型HPV感染分析[J].山西医科大学学报,2017,48(12):1288-1290.
[9]陶瑞,朱丹,孙鹥,等.人乳头瘤病毒感染与宫颈局部细胞因子相关性研究[J].国际检验医学杂志,2017,38(15):2028-2033.
[10]Xue J,Wang Y,Chen C,et al.Effects of Th17 cells and IL-17 in the progression of cervical carcinogenesis with high-risk human papillomavirus infection[J].Cancer Med,2018,7(2):297-306.
[11]洪慧,王鹤.HPV16、58型感染导致宫颈微环境中免疫因子变化及宫颈细胞中病毒整合的初步研究[J].中国免疫学杂志,2014,30(10):1378-1382.
[12]Feng Q,Wei H,Morihara J,et al.Th2 type inflammation promotes the gradual progression of HPV-infected cervical cells to cervical carcinoma[J].Gynecol Oncol,2012,127(2):412-419.
[13]Hamming OJ,Kang L,Svensson A,et al.Crystal structure of interleukin-21 receptor(IL-21R)bound to IL-21 reveals that sugar chain interacting with WSXWS motif is integral part of IL-21R[J].J Biol Chem,2012,287(12):9454-9460.
[14]Davis MR,Zhu Z,Hansen DM,et al.The role of IL-21 in immunity and cancer[J].Cancer Lett,2015,358(2):107-114.
[15]方丽娟.IL-21在肿瘤免疫治疗中的应用及研究进展[J].国际免疫学杂志,2006,29(3):189-193.
[16]Castro Sobrinho JM,Rabelo Santos SH,Fugueiredo Alves RR,et al.Bacterial vaginosis and inflammatory response showed association with severity of cervical neoplasia in HPV-positive women[J].Diagn Cytopathol,2016,44(2):80-86.
[17]杨少岩,吴潇,李杰,等.阴道微环境改变与宫颈病变的相关性分析[J].中国临床保健杂志,2017,20(3):247-250.
[18]陈忆,吴丹,李柱南,等.细菌性阴道病和阴道微生态改变与高危型人乳头瘤病毒感染的临床分析[J].中国医药导报,2018,15(21):86-89.
[19]Godoy-Vitorino F,Romaguera J,Zhao C,et al.Cervicovaginal Fungi and Bacteria Associated With Cervical Intraepithelial Neoplasia and High-Risk Human Papillomavirus Infections in a Hispanic Population[J].Front Microbiol,2018,23(9):2533.
[20]谢建萍,杨志红,伊芳,等.宫颈高危型人乳头瘤病毒感染与阴道菌群及宫颈局部免疫功能的关系[J].中华医院感染学杂志,2017,27(10):2336-2339.