| Cervical cancer is one of the common malignant tumors of female genital tract,which seriously affects the physical and mental health of patients and brings great financial and psychological burden to patients’families.High risk human papilloma virus(hr-HPV)persistent infection is an important cause of cervical cancer.HPV infection mainly occurs in sexually active women.About 80%of women will have been infected with HPV once before the age of 50,while about 90%of patients could completely clear the HPV infection within 2 years,while only a small number of persistent HPV infections.HPV persistent invasion of undifferentiated cervical keratinocytes and differentiation of molecular mechanisms to escape clearance from the host immune response.Given that there are no specific drugs available to completely cleared HPV infections.Clinical treatment is mainly to treat"disease"rather than"cause",that is,to take timely treatment measures when cervical lesions are found,there is no treatment for the"cause".Therefore,if we can clarify the immune escape factors of hr-HPV infection leading to cervical lesions,and early detection of cervical lesions,which provides a theoretical basis for blocking the occurrence and development of cervical precancerous lesions and cervical cancer associated with hr-HPV infection.Immune escape is one of the important causes of cancer development.Tumor suppressor immune cells and factors in tumor microenvironment,such as regulatory T(Treg)cell and transforming growth factor-β(TGF-β)can weaken the function of the body’s immune,decreasing the ability of clearing damaged DNA and abnormal cells,lead to sustained replication of damaged DNA and proliferation of abnormal cells,and then the occurrence and development of cancer.NLR family pyrin domain containing 3protein(NLRP3)is a member of the pattern recognition receptors(PRRs)family,which can recognize pathogen associated molecular patterns(PAMPs)and damage associated molecular patterns(DAMPs)to promote the production and secretion of inflammatory mediators,involvement in inflammatory response and innate immune response.Neutrophil-to-Lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)play an important role in immune and inflammatory response,if the imbalance of expression may lead to the occurrence and development of tumor.It has been demonstrated that PLR and NLR are involved in clinicopathological features and prognosis of endometrial cancer,ovarian cancer and gastritis cancer of numerous malignant tumors.Hr-HPV persistent infection with cervical tissue can lead to cervical lesions or even carcinogenesis,which may be related to hr-HPV inhibition of the body’s immune response.NLR,PLR and NLRP3 have an important role in innate immune response,but there are few studies on the relationship between early cervical lesions and PLR,NLR,NLRP3 with hr-HPV infection.Immunohistochemistry(IHC)was used to detect the expression of NLRP3inflammasome in chronic cervicitis,cervical lesions and early cervical cancer.The expression of PLR,NLR in the preoperative peripheral serum of hr-HPV infected cervical lesions and cervical cancer were detected and analyzed,analysis of the relationship between NLRP3 PLR,NLR expression and clinicopathological factors of early cervical cancer.The purpose of this study is to investigate the situation of innate immunity and inflammation PLR,NLR,NLRP3 in hr-HPV persistent infection of cervical lesions.Retrospective analyzed clinical and pathological datas of 139 patients with surgical treatment or cervical biopsy were selected to the First Hospital of Qinhuangdao during the period from Jan.2019 to Aug.2020,there were 46 cases at early(IA1-IB2,IIA1)cervical cancer,32 cases at high grade squanmous intraepithelial leision(HSIL),30 cases at low grade squamous intraepithlial leision(LSIL)and 31cases at chronic cervicitis,HPV DNA typing of cervical exfoliated cells was performed in the laboratory of our hospital,and at least one hr-HPV typing was positive.The expression of NLRP3 in cervical tissue samples of the above groups by IHC,to analysis the difference of NLRP3 expression in cervical lesions and their correlation with the clinicopathological factors of early cervical cancer.The peripheral serum neutrophil,platelet and lymphocyte counts were collected from all patients within 1 week before operation or biopsy,PLR and NLR were calculated,analysising PLR and NLR expression in preoperative peripheral serum of cervical lesions.Using the ROC curve to determine PLR and NLR critical value of benign and malignant cervical lesions.Discuss the relationship of NLR,PLR expression level and clinicopathological factors of early cervical cancer.IHC results showed that the expression of NLRP3 mainly in the cytoplasm and the expression level of NLRP3 decreased gradually with the severity of cervical lesions.The positive rate of NLRP3 in chronic cervicitis,LSIL,HSIL and early cervical cancer were 45.16%(14/31),40.00%(12/30),28.13%(9/32)and 13.04%(6/46),respectively.The expression level of NLRP3 was significantly downregulated in early cervical cancer group compared to chronic cervicitis group and LSIL group,and the difference was statistically significant(P<0.05).However,there were no significant difference between other groups(P>0.05).Corrrelation between NLRP3 and clinicopathologic factors of early cervical cancer patients,the expression level of NLRP3 in early cervical cancer lesions≤2cm was significantly higher than that in cervical cancer lesions>2cm,the expression differences were statistically significant(P<0.05).However,NLRP3 expression level was no significant related topathological staging,HPV16/18 infection,the degree of pathological differentiation,vascular infiltration,pathological types and depth of cervical interstitial infitration(P>0.05).The expression level of PLR and NLR increased gradually in chronic cervicitis,LSIL,HSIL and early cervical cancer.PLR expression level were significantly higher than chronic cervicitis and LSIL in early cervical cancer,and significantly higher than chronic cervicitis and LSIL in HSIL,the above expression differences were statistically significant(P<0.05).NLR expression level were significantly higher than chronic cervicitis in early cervical cancer,and were significantly higher than chronic cervicitis in HSIL,the above expression differences were statistically significant(P<0.05).However,NLR,PLR expression level were no significant difference between other groups(P>0.05).According to the ROC curve,PLR=133 was selected as the cut-off value to define early cervical cancer and chronic cervicitis.NLR=1.57 was selected as the cut-off value to define early cervical cancer and chronic cervicitis.According to PLR,NLR values,the cervical cancer cases were divided into PLR≥133 and PLR<133,NLR≥1.57 and NLR<1.57.There were no significant difference in the differentiation in clinicopathological factors between the PLR≥133 group and PLR<133 group(P>0.05).There were significant difference in the differentiation degree of early cervical cancer between the NLR≥1.57 group and NLR<1.57 group(P<0.05).there were no significant difference in other clinicopathological factors(P>0.05).Spearman rank correlation analysis showed was correlation between NLR and PLR(r_s=0.453,P<0.05),there were no correlation between PLR and NLRP3,NLR and NLRP3 in early cervical cancer.In conclusion,NLRP3 expression level in early cervical cancer was lower than in chronic cervicitis and LSIL,and the expression levels of PLR and NLR were gradually increased in chronic cervicitis,LSIL,HSIL and early cervical cancer.PLR,NLR and NLRP3 are related to immunity and inflammation,which provide new theoretical ideas for clearancing of HPV and blocking the occurrence and development of cervical lesions. |
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