| Part one:Analysis of pathological results of 871 cases with HPV16 / 18Background and Objective:In 2015,ASCCP recommended that people aged 25 and above can be screened by Cobas HPV.If HPV16/18 is positive,colposcopy should be performed directly.In2019,ASCCP recommended risk-based management of abnormal cervical cancer screening tests and cancer precursors.The purpose of this study is to establish a fine management for HPV16 / 18 positive patients.Method:HPV16/18 positive patients,who were screened at the first affiliated hospital of Nanchang University from January 2016 to January 2018,were biopsied in the suspicious parts under colposcopy.The age,TCT,and the pathological results were collected and analyzed retrospectively.A total of 871 patients were included in this study.Result:Of 871 patients included in this study,469 cases(53.8%)were cervicitis,111cases(12.7%)were cervical intraepithelial neoplasia ?(CIN ?),84 cases(9.6%)were CIN ?,124 cases(14.3%)were CIN ?,83 cases(9.6%)were cervical cancer,all in together 291 cases(33.4%)were CIN ?+ lesions.There were 396 cases of HPV16 positive exclusively,of which 160 cases were CIN ?+ lesions(40.4%),while 119 cases were HPV18 positive exclusively,of which 21 cases(17.6%)were CIN ?+ lesions,the difference is significant(x~2=20.79,P < 0.01).Among all the patients,there were 631 cases who are pre-menopausal,of which194 cases(30.7%)were detected as CIN ?+ lesions,while 240 cases who are post-menopausal,of which 97 cases(40.4%)were detected as CIN ?+ lesions,the difference is significant(x~2=7.31,P < 0.01).HPV16/18 infected patients were grouped further to?20 years,20?25 years,25?30 years,30?35 years,35?40 years,40?45 years,45?50 years,50?55 years,55?60 years,and > 60 years,and the risk of CIN?+ lesions was 10.0%(2/20)?10.0%(2/20)?25.5%(25/98)?26.9%(25/93)?29.5%(39/132)?40.0%(53/156)?45.5%(56/123)?35.3%(30/85)?41.2%(21/51)?52.2%(36/69)respectively.The risk of high grade cervical lesions with HPV 16/18 increased gradually according the the age.The same population were grouped according to the results of TCT as NILM(562 cases),ASCUS(123 cases),LSIL(60 cases),HSIL+(126 cases),and the risk of CIN ?+ lesions was 18.3%(103/562),38.2%(47/123),56.7%(34/60),and 84.9%(107/126)respectively.Therefore,18.3%(103/871)may be missed if screened only by means of TCT.Conclusion:The immediate transfer of patients to colposcopy while HPV16/18 shows positive is very helpful for early detection of cervical intraepithelial neoplasia.For HPV16/18 positive patients with LSIL/ASCUS,colposcopy or rapid treatment is recommended.For HPV16/18 positive patients coupled with HSIL can be recommended for rapid treatment.Part two:Effect of Cobas HPV on the management of ASCUSBackground and Objective:ASCUS(atypical squamous cells of undetermined significance,ASCUS)is the most common abnormal cytological report during cervical screening,accounts for more than 50%,which is also the focus of management.The purpose of this study is to find out how to carry out reasonable clinical management of ASCUS.Method:The patients screened at the first affiliated hospital of Nanchang University from January 2016 to January 2018,whose TCT reports were ASCUS,were collected.A total of 855 cases were included in this study.After referral to colposcopy,biopsy was performed in the suspicious part.The age,HPV test and pathological results were collected and analyzed retrospectively.Result:Of 855 cases included in this study,138 cases(16.1%)were CIN ?+ lesions,77cases(8.8%)were CIN ?+ lesions.Among 855 cases,700 cases were tested by HPV simultaneously,219 cases were HPV negative,in which the risk of CIN ?+ lesions was 4.1%(9 / 219),the risk of CIN ?+ lesions was 0.9%(2 / 219),481 cases were HPV positive,the risk of CIN ?+ lesions was 22%(106 / 481),and the risk of CIN?+ lesions was 12.7%(61 / 481).401 cases were detected by Cobas HPV,110 cases were HPV16 / 18 positive,the risk of CIN ?+ lesions was 37.3%(41 / 110),and the risk of CIN ?+ lesions was22.7%(25 / 110).291 cases were HPV other types positive,the risk of CIN ?+ and CIN ?+ were 15.8%(46/291),CIN ?+(24/291)respectively.Among 253 postmenopausal patients,the risk of CIN ?+ and CIN ? + were17.0%(43 / 253)and 9.1%(23 / 253),while in the 602 cases of premenopausal patienst,the risk of CIN ?+ and CIN ?+ were 15.8%(95 / 602)and 9.0%(54 / 602)respectively.855 cases of ASCUS were further divided into ? 30 years groups and > 30 years group,the risk of CIN ?+ and CIN ?+ were 7.8%(10 / 128)and 3.1%(4 / 128)in the younger group,which were significantly lower than those of older group,which the risk of CIN ?+ and CIN ?+ were 17.6%(128 / 727)and 10.0%(73 / 727)(P<0.05).Conclusion:ASCUS is preferred to be triaged by hr HPV test,when HPV16/18 shows positive,it should be referred to colposcopy immediately.The management of ASCUS with other high-risk HPV should be based on previous screening history and age.The risk of CIN ?+ lesions in young women is relatively low,so prudent biopsy is recommended.Part three:The pathogenesis of mi R-145-5p/FSCN1 in cervical cancerBackground and Objective:Micro RNA(miRNA),a class of short non-coding RNAs of about 20 nucleotides in length,repress the expression of target m RNA by catalyzing m RNA or by inhibiting m RNA translation.Mi RNA-145 was found to be reduced in gastric,ovarian,breast,prostate,and lung cancers,which was thought to be a tumor suppressor.FSCN1,(fascin actin-bundling protein 1,FSCN1),which has been preferentially localized to malignant cells at the deep tumor margin(invasive front),enhances the migratory and invasive properties of normal and neoplastic cells through the stabilization of cytoplasmic actin filaments.In this study,we aim to explore whether miRNA-145-5p/FSCN1 is involved in the development of cervical cancer.Method:A total of 40 patients with cervical squamous cell carcinoma were collected from January 2016 to January 2018 in the first affiliated hospital of Nanchang University.The cancer tissues were taken,and normal tissues 0.5cm away from the cancer tissues were taken as self-control.The clinicopathological data was collected and analyzed.The cervical cell lines(Ect1/E6E7),Hela cell and C33 a cell were cultured.Real-time PCR(RT-PCR)was used to detect the expression of miRNA-145-5p and FSCN1 in tissues and cells.The miRNA-145-5p mimics and inhibitors were cultured with Ect1/ E6E7 and He La cells,the expression of miRNA-145-5p and FSCN1 were detected by RT-PCR,the expression of FSCN1 is detected by western blotting,and the cell viability was detected by CCK-8 kit.Result:The expression of miRNA-145-5p in cervical cancer tissues was significantly lower than that in normal tissues adjacent to cervical cancer(P<0.05).The expression of miRNA-145-5p in He La and C33 a cells was significantly lower than that in Ect1/E6E7 cells(P<0.05).Mi RNA-145-5p expression was not significantly correlated with age,tumor size(P>0.05),but was significantly correlated with tumor grade and lymph node metastasis(P<0.05).The expression of FSCN1 in cervical cancer tissues was significantly higher than that in normal tissues adjacent to cervical cancer(P < 0.05).The expression of FSCN1 in He La and C33 a cells was significantly higher than that in Ect1/E6E7 cells(P<0.05).After transfected of He La cells and Ect1/E6E7 cells with miRNA-145-5p mimics,the expression of miRNA-145-5p increased significantly(P<0.001),while the expression of FSCN1 decreased significantly(P<0.05),and the cell survival rate decreased significantly(P<0.05).After transfeced of He La cells and Ect1/E6E7 cells with miRNA-145-5p inhibitors,the expression of FSCN1 increased significantly(P<0.001),and the cell survival rate increased significantly(P<0.01).Conclusion:The expression of miRNA-145-5p was significantly downregulated in cervical cancer,and was significantly correlated with tumor grade and lymph node metastasis.miRNA-145-5p is a potential tumor suppressor gene,which might regulate the invasion and metastasis of cervical cancer through FSCN1. |
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