| Objective:To research the function of cervical mucosal cytokines in the process of body's resistance of cervical high-risk human papillomavirus(HR-HPV)infection and in the progression of cervical neoplasia,and analyze the immune response of different types of HR-HPV.Objective to screen the cytokine,which differently expressed and may exert immune function between transient and persistent infection and between low grade squamous intraepithelial lesion(LSIL)and high grade squamous intraepithelial lesion(HSIL),and to explore the immune mechanism of persistent HR-HPV infection and progression of cervical lesions.So as to provide new immune markers for distinguishing the status of HR-HPV infection and the degree of cervical lesions,and provides an immunological basis for the prevention of persistent infection and cervical lesions in HR-HPV.Method:Patients enrolled were selected in Colposcopy outpatient clinic of Tianjin Central Obstetrics and Gynecology Hospital from December 2015 to May 2016,and according to outcome of HC-II,150 subjects were selected.Among them,148 patients had TCT test and all the patients were examined by colposcopy.Every participant signed informed consent and the cervical vaginal lavage(CVL)and cervical exfoliated cell were obtained in the clinic as specimens.Cervical exfoliated cell samples were used for DNA extraction.Detection of 15 kinds of HR-HPV type(HPV16,18,31,33,35,39,45,51,52,56,58,59,66,68,69)was performed with nested PCR and later production were sequenced by pyrosequencing.9 cytokines(IL-1?,IL-2,IL-4,IL-8,IL-10,IL-12,IL-21,TNF-? and IFN-?)were tested by multiple microsphere technique from CVL to analyze the local cervical immune status.The SPSS.23 software was used to the analysis of variance(ANOVA)and the correlation of the data.The relationship between levels of cytokines and different HPV infection state,different HPV DNA load,different HR-HPV types,different HR-HPV cytology and different cervical biopsy results were analysed from HPV-DNA,cytological and histological level.Result:1.HR-HPV type were detected in 114 cases with HR-HPV infection,94(82.46%)cases were single HR-HPV type infection,of which,37(30.9%)cases were type HPV16 infection.20(17.54%)cases were mixed infection,of which,16(80%)cases were mixed infection of HPV16 and other types of HPV,included HPV18,HPV31,HPV52,HPV56,HPV58.2.In inflammatory group,LSIL and HSIL,the incidence of HPV16 were 20 %,30 %,47 % respectively;the incidence of HPV18 were 26.7 %,22.5 %,22.4 %respectively;the incidence of other HR-HPV were 53.3 %,47.5 %,30.6 %,respectively.In this study,HPV16 is the major type of cervical lesions.3.In the HPV16 and HPV18,the level of IL-8 was significantly higher than that of other cytokines(P<0.05),while this difference was not exit in HPV31,HPV33,HPV39,HPV52,HPV56 and HPV58 type(P > 0.05).4.Between 36 cases of HR-HPV transient infection and 40 cases of HR-HPV persistent infection,there was significant difference in the expression of IL-1?(P=0.041),the level of IL-1? in persistent infection group was significantly higher than that of transient infection group,while there was no significant correlation of this difference(r=0.136,P =0.327).5.Between 36 cases of LSIL and 38 cases of HSIL,there was significant difference in the expression of IL-1?,L-10,IL-21 and TNF-?(P value was 0.01,0.008,0.046 and 0.019 respectively),and their level in HSIL was significantly higher than that of LSIL.Furthermore,the level of TNF-? and IL-1? were positively correlated with the progression of cervical neoplasia(r=0.474,P= 0.001 and r=0.433,P=0.015,respectively).6.Compared with the regulation factors of lymphocyte(IL-2,IL-4,IL-21)and immune inflammatory factors(IL-10,IL-12,IFN-?),the expression of proinflammatory cytokines(IL-1?,IL-8,TNF-?)in four groups(HR-HPV transient and persistent infection,LSIL and HSIL)were significantly higher than those of the other 2 kinds of cytokine(P value were less than 0.001).Conclusion:1.The majority of HPV infected individuals were simple infection,of which HPV16 was the most common type followed by HPV 18.With the occurrenceand development of cervical lesions,the infection rate of HPV16 also increased,the infection rate of HPV 18 was stable,and the infection rate of other types of HR-HPV decreased.2.Contrasted with other HR-HPV types,HPV16 and HPV18 caused different cervical mucosal immune state,high level of IL-8 may conducive to their persistent infection and the occurrence of cervical lesions.3.IL-1? may provide favorable local mucosal immune microenvironment for persistent infection of HR-HPV.4.The high level of IL-1?,IL-10,IL-21 and TNF-? was not conducive to the maintenance of LSIL,which provides favorable immune condition for the development from LSIL to HSIL,and the level of IL-1? and TNF-? were positively correlated with the progression of cervical neoplasia.5.Proinflammatory cytokines(IL-1?,IL-8,TNF-?)played an important role in the process of cervical HR-HPV infection and the progression of cervical neoplasia. |
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