| BackgroundCervical cancer is one of the three major malignant tumors in the female reproductive system.Its occurrence and development are highly tight with HPV infection,and it takes an average of 8-12 years for HPV infection to eventually develop into cervical cancer via LSIL and HSIL,therefore,the diagnosis and treatment of CIN becomes one of the keys to prevent cervical cancer.Because of the higher progression rate in HSIL compared with LSIL,surgery is advocated for HSIL,and cervical conization is the best choice for most patients.Conization plays a role both in the removal of SIL lesions and HPV virus clearance in some degree,however even after treatment,risk of being cervical cancer is still 4-5 times higher than the normal,which requires close follow-up.Persistent HR-HPV infection is a risk factor for recurrence after surgery.Therefore,HPV outcome after HSIL conization affects patients’ prognosis in a long term.Vaginal microecology is composed of four parts: anatomical structure,periodic endocrine changes,vaginal microimmunity and microbial flora.In recent years,it has been found that vaginal microecological imbalance is related to the occurrence and development of cervical lesions closely.At present,vaginal microecological testing has been widely used in clinical practice,and the status of vaginal flora can be evaluated comprehensively from morphology(bacterial density,diversity,dominant bacteria,WBC count,Nugent score,etc.)and function(pH,hydrogen peroxide,sialic anhydride enzymes,leukocyte esterase,β-glucuronidase,acetylglucosidase).Patients with imbalanced vaginal flora are more susceptible to HPV,and their ability to clear themselves after infection is also reduced.Further,as a chronic stimulus,persistent HPV infection disrupts the vaginal microecology,so that a vicious cycle occurs,and then cervical lesions generate.Studies have shown that HPV clearance also depends on vaginal microimmunity.CD4+/CD8+ and Th1/Th2 are important indicators of immune balance.Under antigen stimulation,CD4+T lymphocytes are activated and differentiate into Th1 and Th2 cells.Th1 secretes IL-2,IL-12,IFN-γ and TNF-α,inducing cellular immunity and suppressing humoral immunity,and playing a major role in antitumor and anti-virus;Th2 cells express IL-4,IL-5,IL-6 and IL-10,etc.,are mainly involved in humoral immunity and suppress cellular immune response.Th1/Th2 balance is essential for establishing a good vaginal immune environment.Th1/Th2 balance was broken in people with abnormal vaginal microecology,and even it appears in HPV infected patients that Th1 drifts to Th2 cells.Disorder of T cell subsets increases the risk of persistent HPV infection,weakens abilities of HPV clearance,tumor immune surveillance and defense.Therefore,the vaginal microecology is closely related to cervical lesions,which can affect the outcome of consignation of HSIL patients in a way.There is a large population of patients with cervical lesions in China,but for HSIL,there are few comprehensive considerations of both vaginal flora and microimmunization in pre-operation,and HPV outcomes after surgery in China.ObjectiveTo compare the preoperative vaginal flora and its morphological function corresponding to different outcomes of HPV after conization in HSIL.To explore the characteristics of preoperative vaginal microimmunity in different postoperative HPV outcomes.To analyze the correlation between postoperative HPV outcome and vaginal microecology represented by vaginal flora and microimmunity.MethodsAccording to the inclusion and exclusion criteria,cases accepting cervical conization because of HSIL were selected from the Second Hospital of Jilin University from October 2018 to October 2019.General clinical data were gathered,and before surgery,vaginal secretions were collected for microecology test,vaginal lavage fluid as well.According to postoperative HR-HPV outcomes,a total of 61 HR-HPV negative patients(negative negative group)and 30 positive patients(positive group)were included.Another 57 patients were included as the control group who were negative for HPV and TCT during the physical examination.ELISA was used to detect the concentration of Th1 cytokine IL-2 and Th2 cytokine IL-10 in vaginal lavage fluid.We used statistical methods to compare vaginal flora,morphology,functional indicators,and IL-2,IL-10 and IL-2/IL-10 ratios in the lavage fluid between the three groups,and analyze the differences.Logistic regression analysis summarized the correlation between the different indicators and HPV outcomes after conization in HSIL.Results1.The general clinical data(age,menopausal status(yes / no),preoperative HPV16/18 as well as other 12 types of HR-HPV values,TCT,and surgical procedures(cold knife,LEEP,supplement total hysterectomy),pathological type)were not significantly different between the control group,negative group and positive group.2.Among the indicators of preoperative vaginal flora morphology,WBC count and Nugent score of the control group were significantly lower than those of negative group and positive group,and the differences were statistically significant,while there was no significant difference between negative group and positive group.There were no significant differences in population density,diversity,and dominant bacteria among the three groups.3.Among the functional indicators,the preoperative leukocyte esterase expression and pH value of the positive group were significantly higher than those of the negative group and control group,and the differences were statistically significant;the hydrogen peroxide level of the control group were significantly lower than those of the negative group,while the difference between negative and positive group of HSIL was not statistically significant;the remaining functional indicators such as sialidase,β-glucuronidase,acetylglucosidase,and comprehensive interpretation types as well as special infection,showed no significant difference among the three groups.4.The IL-2 concentration in preoperative vaginal lavage fluid had no significant difference between the three groups.IL-10 concentration in the positive group was significantly higher than that in both negative and control groups.In addition,ratio of IL-2/IL-10 was lower than that in negative group and control group,which was statistically significant.5.Preoperative vaginal leukocyte esterase and pH are independent risk factors for HR-HPV persistence after surgery in HSIL(OR = 5.738> 1,95% CI = 1.179-27.933,P = 0.030;OR = 21.549> 1,95 % CI = 1.386-334.954,P = 0.028),while IL-2/IL-10 is an independent protective factor(OR = 0.014 <1,95% CI = 0-0.918,P = 0.045).Conclusion1.The outcome of postoperative HR-HPV in HISL patients is related to the preoperative vaginal microecological functional status and vaginal microimmunity.2.The levels of leukocyte esterase,PH value and vaginal lavage fluid IL-10 concentration in positive group were significantly higher than those in negative group and control group,and in positive group IL-2/IL-10 ratio was significantly lower in negative and control group.In the vaginal microecology,low functional lactic acid bacteria and an inflammatory state,hyperfunction of Th2 cells in vaginal microimmunity,and Th1/Th2 cell drift are all related to the difficulty of postoperative HR-HPV clearance in patients with HSIL.3.Leukocyte esterase and PH are independent risk factors for HRHPV persistence after surgery in HSIL.The higher the degree of leukocyte esterase before surgery and the higher the PH value,the greater the risk of HR-HPV persistence after surgery.IL-2/IL-10 is an independent protective factor for postoperative persistent HR-HPV infection.The higher the preoperatinal IL-2/IL-10 ratio,the lower the risk of sustained positive HR-HPV after surgery.Preoperative vaginal microecological function and Th1/Th2 cell immune balance were significantly correlated with the outcomes of postoperative HR-HPV. |
