The Application Of "Three Steps" Screening Technique In Cervical Intraepithelial Neoplasia

Background Cervical intraepithelial neoplasia(CIN)is a group of lesions that occur frequently in the cervical columnar junction area.It is a general term for cervical precancerous lesions.It reflects the continuous process of cervical pathological changes from atypical hyperplasia to cervical cancer.The disease is most common among young women of childbearing age,most of whom are 25~35 years old.CIN is not an one-way development,but there are three different trends: one is natural regression,the two are persistent disease,the tree is progression or canceration.In fact,most of CIN can be self subsided.About 70%CINI will disappear within a year,and 90%CINI will disappear within two years.50%CINII can also disappear in two years without treatment.However,part of CIN can progress to cervical cancer,where 11%CINI and 22%CINII can progress to cervical cancer in situ(CIS).20%CINII will advance to CINIII,and 5%CINII can progress to cervical invasive cancer.It usually takes 10~15 years to develop invasive cervical cancer from CIN.Depending on the characteristics of epithelial dysplasia,CIN is divided into 3 levels,namely CINI,CINII and CINIII.CINI and CINII represent mild and moderate atypical hyperplasia of the cervix,respectively.CINIII includes severe cervical dysplasia and / or cervical carcinoma in situ.In 2012,the American colposcopy Association(ASCCP)updated the original three classification of cervical intraepithelial neoplasia to the two classification of cervical cytology(LSIL,HSIL),the low grade squamous intraepithelial lesion of the cervix(LSIL)and the high grade squamous intraepithelial lesion of the cervix(HSIL).In 2014,WHO also used this method in the classification of female genital organs.At present,the diagnosis of cervical cancer and precancerous lesions is based primarily on the combination of liquid based cytology and HPV screening,the examination and localization of colposcopy,and the "three steps" principle in the diagnosis of pathological and living tissue.The earliest Pap smear as a traditional screening method for cervical cancer has a history of over 60 years,and plays a major role in reducing the mortality of cervical cancer.But the traditional pasteurized smear has some shortcomings.That is,more than 80% of the cells collected will be discarded on the brush,and more than 50% cell smears affect the film because of poor quality.The false negative rate can reach 20% ~ 40%,which rides the prevention and cure of cervical cancer unsatisfactory.With the innovation of science and technology,liquid based cytology,as a new screening method for cervical cancer,not only overcomes the defects of Pap smear production,but also improves the quality and sensitivity of the film,reduces the false negative rate obviously,greatly reduces the incidence and mortality of cervical cancer,and has been widely used in clinic.Depending on related literature,the sensitivity of liquid based cytology is 60%.But in clinical,most doctors only pay attention to the use of liquid based cytology,ignoring the application of HPV-DNA,resulting in missed diagnosis in the clinic.At the same time,due to the popularity and application of screening,there is an over treatment phenomenon for CIN.In this study,the accuracy of TCT combined with HPV-DNA and the diagnostic accuracy of colposcopy biopsy and pathological results after CKC were retrospectively analyzed,and the relationship between the marginal state and the residual status was compared.1.Objective: to compare the accuracy of TCT combined with HPV-DNA screening with single cytology or HPV,and the coincidence rate of pathological diagnosis after colposcopy and CKC,and further compare the relationship between the residual status of the lesions after the hysterectomy and the margin of CKC after the hysterectomy and the screening and treatment for the precancerous lesions of the cervix.For data to support.2.Methods: 962 cases of cervical disease were collected from 2009 to December 2017 in our hospital.30 cases of cervicitis and 240 cases of cervical cancer were abducted by colposcopy pathological biopsy.The data of the remaining 692 patients with CIN were analyzed retrospectively.Owing to the lack of partial data in some patients,a total of 543 patients with liquid based cytology and 409 cases of HPV results were collected and analyzed.First,the accuracy of TCT combined with HPV and single detection method before colposcopy biopsy was compared.Then according to pathological results after cold knife conization,the coincidence rate of colposcopy biopsy results was compared.Then a total hysterectomy or follow-up was performed after cervical conization to compare the relationship between incisal margin and residual.Finally,distribution of P16 and Ki67 in cervical intraepithelial neoplasia and the age distribution of patients after cold knife conization were analyzed.3.Results: A total of 692 patients with CIN were collected.Due to partial loss of partial data,a total of 543 patients with liquid based cytology and 409 cases of HPV positive results were collected and analyzed.507 patients were screened with cervical fluid based cytology TCT,ASCUS96,LSIL105,ASC-H88,HSIL218,and CINI36 cases,CINII78 cases,CINIII351 cases and SCC42 cases after biopsy by colposcopy.In ASCUS,pathological results of colposcopy were CINI,CINII,CINIII and SCC ratio were 13/96(13.5%),23/96(24%),52/96(54.2%),8/96(8.3%).In LSIL,pathological results of colposcopy were CINI,CINII,CINIII and SCC ratio were 12/105(11.4%),18/105(17.1%),67/105(63.8%),8/105(7.6%).In ASC-H,the immunological results of colposcopy were CINI,CINII,CINIII and SCC respectively,8/88(9.1%),18/88(20.5%),56/88(63.6%),6/88(6.8%).In HSIL,pathological results of colposcopy were CINI,CINII,CINIII and SCC ratio were 3/218(1.4%),19/218(8.7%),176/218(80.7%),20/218(9.2%).In TCT negative,the pathological results of colposcopy were CINI,CINII,CINIII and SCC respectively,4/36(11.1%),6/36(16.7%),19/36(52.8%),7/36(9%).Of 507 TCT positive cases,360 were positive for HPV,and the positive rate was 360/507(71%).Of 36 cases with TCT negative,19 were positive for HPV,and the positive rate was 19/36(52.78%).Among 96 patients with ASCUS,46 cases were positive for HPV,the positive rate was 46/96(47.92%);in 105 patients with LSIL,HPV positive was 80,the positive rate was 80/105(76.19%);in 88 patients with ASC-H,HPV positive was 56 cases,the positive rate was 56/88(63.64%),and 218 cytology was HSIL.Among them,178 cases were positive for HPV,and the positive rate was 178/218(81.65%).Of 379 high-risk HPV positive patients,type HPV16 accounted for 148 cases,the percentage was 148/379(39.05%),HPV18 accounted for 67 cases,the percentage was 67/379(17.68%),and the other 12 high-risk types of HPV were 164 cases,the percentage was 164/379(43.27%).Among them,the other 12 high risk types of HPV accounted for the largest proportion,followed by HPV16 and HPV18.In 65 cases of ASCUS combined with HPV positive,65 cases were positive by colposcopy,and the positive rate was 65/65(100%).In 68 cases of LSIL combined with HPV positive,68 cases were positive by colposcopy,and the positive rate was 68/68(100%).In 73 cases of ASC-H combined with HPV positive,73 cases were positive by colposcopy,and the positive rate was 73/73(100%).HSIL combined with HPV positive in 154 patients,colposcopy pathology results were positive in 154 cases,the positive rate was 154/154(100%).Among 19 patients with TCT negative and HPV positive,10 were positive for HPV16,1 for HPV18 and 8 by 12 other high-risk groups.The pathological results of colposcopy were CINI1 cases,the positive rate was 1/19(5.2%),CINII9 cases,the positive rate was 9/19(47.4%);CINIII9 cases,the positive rate was 9/19(47.4%);SCC0 cases.TCT positive combined with HPV negative in 30 cases,ASCUS5 cases,LSIL8 cases,ASC-H6 cases,HSIL11 cases.The pathological results of colposcopy were CINI7 cases,the positive rate was 7/30(23.3%);CINII6 cases,the positive rate was 6/30(20%);CINIII17 cases,the positive rate was 17/30(56.7%);SCC0 cases. The diagnosis of 692 patients with colposcopy showed that CINI51,CINII137,CINIII504 and CKC were diagnosed as chronic cervicitis,15 cases of chronic cervicitis,CINI46,CINII115,CINIII449,and early invasive cancer in 67 cases.There were 527 cases of the postoperative diagnosis,which accounted for 76.2%(527/692)of the total number of cases;the diagnosis level rose in 113 cases,accounting for 16.3%(113/692)of the total number,and the diagnosis grade decreased in 52 cases,accounting for 7.5% of the total number of cases(52/692).29 cases of grade CINI,56.9%(29/51),85 cases of grade CINII,62%(85/137)of the same level,413 cases of CINIII,81.9%(413/504)of the same level.Of 692 patients with cervical intraepithelial neoplasia,74 had positive margins after CKC,and the positive margin was 10.7%(74/692).A total of 31 patients with positive conical resection margin underwent total hysterectomy.25 cases were residual lesions and 6 cases were negative after operation.The residual rate was 25/31(80.6%).43 patients were followed up after the operation.During the 3,6,12,and 24 months follow-up period after CKC,4 cases of CIN were followed up in our hospital after six months of follow-up.In 6 cases with CINII,the negative rate of HPV was 1/6(16.7%),3/6(50%),4/6(66.7%),5/6(83.3%),and HPV conversion rate in 33 patients with positive marginal lesions was 5,respectively,5./33(15.2%),12/33(36.4%),23/33(69.7%),29/33(87.9%).During the follow-up period of 24 months,the negative rate of HPV increased with the prolongation of CINII/III.At 24 months after the operation,the negative rate was over 80%.In addition,during the 3,6,12,and 24 month follow-up period of CKC,6 cases with CINII were 2/6(33.3%),4/6(66.7%),4/6(66.7%),6/6(100%),and 33 cases of CINIII with CINIII,33 cases were 8/33(24.2%),15/33(45.5%),26/33(78.8%),31,respectively./33(93.9%).During the follow-up period of 24 months,the negative rate of TCT increased with the prolongation of CINII/III.At 24 months after the operation,the negative rate was over 90%.. After 6 months of follow-up,there were 24 cases of HPV positive and 20 cases of TCT positive after CKC.Colposcopy of cervical biopsy was performed on these 24 patients.Pathological findings were CINII7,CINIII17 and CKC two conization.After colposcopy,the pathological findings of CINII were residual or recurred in 1 patients after two conization of CKC.No residual or recurrence occurred in 6 patients.After colposcopy,the pathological findings of CINIII were residual or recurred in 4 patients after two conization of CKC.No residual or recurrence occurred in 13 patients.Pathological findings of two high-grade lesions after CKC showed that the residual or recurrent rate was 5/24(20.8%).In this study,the age of cervical intraepithelial neoplasia is 25~44 years old,accounting for 80.8% of all cases,which is relatively common in 30~34 years of age,accounting for 28.5%,and 35~39 years old,accounting for 24.4%.In this study,the positive rates of P16 in CINI,CINII and CINIII were 29/46(63%),93/115(80.9%),and 449/449(100%).The positive rates of Ki67 in CINI,CINII and CINIII were 35/46(76.1%),89.6%,100%.4.Conclusion: 1.In this study,TCT combined with HPV-DNA has higher accuracy and higher collocation rate for colposcopy.2.In this study,there was a significant correlation between the marginal status and residual lesions.3.P16 and Ki67 have high auxiliary value for the diagnosis of cervical lesions in clinical practice,which can effectively reduce over treatment in clinical work.4.cervical intraepithelial neoplasia is prevalent in young women of childbearing age.