Study On Factors Associated With Pregnancy Complicated With High-grade Squamous Epithelial Lesions Of The Cervix

Objective:With the relaxation of the the universal two-child policy,the incidence rate of cervical diseases in pregnancy is higher,especially in pregnancy with squamous intraepithelial lesion(SIL).Cervical SIL has previously been referred as "cervical intraepithelial neoplasia"(cervical intraepithelial neoplasia,CIN).This study retrospectively analyzed the clinical reversal of high grade squamous intraepithelial lesion(HSIL)in pregnancy and the pregnancy outcome of pregnant women,so as to provide a more reasonable clinical diagnosis and treatment plan for pregnant women with pregnancy complicated with HSIL,it provides a new way of diagnosis and treatment to reduce the incidence of adverse outcomes in clinical practice.At the same time,according to the results of postpartum pathological examination,the research further analyzed whether the status of HSIL pregnancy would be progressive,persistent or reversed,and the related high-risk factors were also analyzed.Methods:The research first retrospectively analyzed all the cases of pregnant women who underwent routine obstetric examination in the Qianfoshan Hospital of Shandong Province and 960 Hospital of Chinese people’s Liberation Army Obstetrics Clinic and delivered in our hospital from January 1,2016 to November 30,2019.This process includes not checked TCT and human papilloma virus or HPV test one year before pregnancyand in pregnancy,TCT was performed in the first prenatal examination,and HPV was performed in the abnormal cases,the research also further evaluated the patients with high-risk HPV positive or abnormal TCT results by colposcopy and multi-point pathological biopsy for suspicious lesions.Colposcopy was performed again 6-10 weeks after delivery,and multi-point pathological biopsy was performed for suspicious lesions.The general information,pregnancy and delivery history,HPV examination results,TCT examination results,delivery mode,prenatal colposcopy and cervical biopsy pathological results,postpartum colposcopy and cervical biopsy pathological results were all collected in detail.With the help of SPSS software(version 22.0;SPSS Inc.,Chicago,IL,USA),statistics data were extracted from the following aspects:analysis of different gestational weeks of biopsy on pregnancy outcomes and complications;analysis of high-risk HPV persistent and non persistent infection on cervical lesions;analysis of the effect of different types of high-risk HPV(16,18 and other high-risk types)on cervical lesions;analysis of the effect of delivery mode(natural birth,cesarean section)on cervical lesions;analysis of the effect of different prenatal cytological grading results(≥HSIL,<HSIL)on cervical lesions;analysis of the changes of pathological results before and after delivery to determine whether the status of pregnancy complicated with cervical lesions turned progressed,sustained or reversed,and related high-risk factors.Result:1.A total of 160 pregnant women with abnormal TCT or positive results of high-risk HPV were included in this study.The average age was 30.2 years(19-42 years)with HSIL diagnosed by cervical multi-point biopsy.2.Out of those 160 pregnant women,149(93.13%)were infected with HPV;144(90.00%)were high-risk HPV infection,and 86(59.72%)were infected with HPV16 or 18.The results of prenatal TCT were as follows:26 cases(16.25%)were atypical squamous cells of undetermined significance(ASC-US);14 cases(8.75%)were low grade intraepithelial lesion(LSIL);97 cases(60.63%)were high grade squamous intraepithelial lesion(LSIL);23 cases(14.38%)were atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesions(ASC-H).3.All HSIL pregnant women received TCT and HPV examination again 6-10 weeks after delivery.TCT results were as follows:32 cases(20.00%)were normal;27 cases(16.88%)were ASC-US;5 cases(3.13%)were ASC-H;33 cases(20.63%)were LSIL and 63 cases(39.38%)were HSIL.There were 144 cases(90.00%)of HPV infection in postpartum period,which was 5 cases less than that of prenatal period.Among them,104 cases(65.00%)were high-risk HPV infection,and 40 cases were lower than that of prenatal period.Among them,66 cases were infected with HPV genotype 16 or 18,which means there were 20 cases less than that of prenatal.4.Among the 160 postpartum women,32 cases had normal TCT,in which no further examination was conducted,A total of 128 women underwent colposcopic biopsy.Among them,104 cases underwent cervical conization,including 32 cases of LEEP,72 cases of cold knife conization,and 10 cases insisted on follow-up after full notification.A total of 128 postpartum women underwent colposcopic biopsy,among which the final pathological results of 7 cases(5.47%)were normal,CIN 1 in 7 cases(5.47%),CIN 2 in 42 cases(32.81%),CIN 3 in 69 cases(53.91%).3 patients(2.34%)had cervical cancer(stage IA1)and their pathological findings of cervical conization showed stage I A1(interstitial infiltration≤3mm,width≤7mm,no lymphatic vessel space infiltration)and they strongly required to preserve reproductive function.Their ages were 27 years(G4P1L1A2),30 years(G5P1L1A4)and 31 years(G3P2L2A1).After full disclosure,regular postoperative follow-up was conducted.5.The compared pathology results of prenatal and postpartum showed that 48 cases of prenatal CIN 2,11 cases of normal postpartum TCT+pathology,5 cases of CIN 1,23 cases of CIN 2,8 cases of CIN 3,1 case of cervical cancer(stage IA1),112 cases of prenatal CIN 3,28 cases of normal postpartum TCT+pathology,2 cases of CIN 1,19 cases of CIN 2,61 cases of CIN 3 and 2 cases of cervical cancer(stage IA1).Postpartum HSIL compared with prenatal HSIL biopsies,there were 3 cases of progression,111 cases of persistence,and 46 cases recovered.There was significant difference between prenatal HSIL(CIN 2+CIN 3)and postpartum HSIL(CIN 2+CIN 3)(P<0.05).6.Among the 77 pregnant women who underwent colposcopy cervical biopsy in early pregnancy(<12weeks),48 cases(62.34%)had full-term spontaneous delivery,and 29 cases(37.66%)had full-term cesarean section,including 1 case(1.30%)of postpartum hemorrhage due to uterine atony.77 cases(72.73%)of pregnant women underwent colposcopy cervical biopsy in the second trimester(12-<28weeks),with 56 cases(72.73%)of full-term spontaneous delivery and 21 cases(27.27%)of full-term cesarean section.There was one case(1.30%)of premature rupture of membranes which was considered to be caused by bacterial vaginitis,1 case(1.30%)of spontaneous labor postpartum hemorrhage which was considered as acute labor soft birth canal laceration.In late pregnancy(28 weeks to 37 weeks),6 pregnant women underwent colposcopy cervical biopsy with 4 cases(66.67%)of full-term spontaneous delivery and 2 cases(33.33%)of full-term cesarean section.There was no significant difference in pregnancy outcome and complications(natural birth,cesarean section,abortion,premature delivery and premature rupture of membranes,postpartum hemorrhage,third degree contamination of amniotic fluid)between early pregnancy(<12weeks)and second trimester(12-<28weeks)(P>0.05);There was no significant difference in pregnancy outcome and complications(spontaneous delivery,cesarean section,abortion,premature delivery and premature rupture of membranes,postpartum hemorrhage,third degree contamination of amniotic fluid)between early pregnancy(<12 weeks)and late pregnancy(28weeks-37weeks)(P>0.05);There was no significant difference in pregnancy outcome and complications(natural birth,cesarean section,abortion,premature delivery and premature rupture of membranes,postpartum hemorrhage,third degree contamination of amniotic fluid)between second trimester(12-<28weeks)and late pregnancy(28 weeks-37 weeks)(P>0.05).7.The influence of persistent and non persistent high-risk HPV infection on cervical lesions:There were 104 cases of persistent high-risk HPV infection,with 8 cases of normal HPV and pathology,3 cases of CIN 1,35 cases of CIN 2,55 cases of CIN 3,and 3 cases of cervical cancer;56 cases were non persistent high-risk HPV infection,with 31 cases of normal HPV and pathology,4 cases of CIN 1,7 cases of CIN 2,14 cases of CIN 3,and 0 case of cervical cancer.The impact difference between high risk HPV persistent and non persistent infection on postpartum HSIL was statistically significant(P<0.05).8.The influence of different types of high-risk HPV(16,18 and other high-risk types)on cervical lesions:There were 86 cases of HPV(type 16 and 18)infection in prenatal period.After delivery,9 cases were of normal HPV and pathology,3 cases of CIN 1,27 cases of CIN 2,45 cases of CIN 3,2 cases of cervical cancer(all in stage Ⅰ A1,1 case of HPV 16 infection,1 case of HPV 18 infection).There were 58 cases of prenatal CIN 2+infection of HPV(except for other high-risk types of type 16 and 18)and 14 of them were cases of postpartum HPV and pathological normal,with 4 cases of CIN 1,15 cases of CIN 2,24 cases of CIN 3,and 1 case of cervical cancer(stage IA1,HPV-31 infection).There was no significant difference in the effect of different types of high-risk HPV(16,18 and other high-risk types)on postpartum HSIL(P>0.05).9.The effect of delivery mode(natural birth,cesarean section)on cervical lesions:There were 108 cases of spontaneous delivery,33 cases of normal postpartum TCT and histopathological diagnosis,4 cases of CIN 1,23 cases of CIN 2,48 cases of CIN 3,0 case of cervical cancer.52 cases had cesarean section,with 6 cases of normal postpartum TCT and histopathological diagnosis,3 cases of CIN 1,19 cases of CIN 2,21 cases of CIN 3,and 3 cases of cervical cancer(stage IA1).There was no significant difference in the effect of delivery mode(natural delivery and cesarean section)on postpartum HSIL(P>0.05).10.The influence of different prenatal cytological grading results(≥HSIL,<HSIL)on cervical lesions:97 cases were of prenatal cytological grade>HSIL,with1 case of normal postpartum TCT and histopathological diagnosis;5 cases of CIN 1;33 cases of CIN 2;55 cases of CIN 3;3 cases of cervical cancer.63 cases were of prenatal cytological grade<HSIL,with 38 cases of normal postpartum TCT and histopathological diagnosis,2 cases of CIN 1,9 cases of CIN 2,,14 cases of CIN 3,and 0 cases of cervical cancer.There were significant differences in the influence of prenatal cytological grading(≥HSIL,<HSIL)on postpartum HSIL(P<0.05).11.To evaluate the risk factors(age,smoking,parity,persistent high risk HPV infection)by univariate logistic regression analysis,the results showed that birth time(OR 3.623;95%CI 1.031-12.728;P=0.045)and persistent high risk HPV infection(OR 11.848;95%CI 5.293-26.525;P<0.001)were the significant variables for the persistence of CIN 2+in pregnancy.Further multivariate logistic regression analysis showed that when factors like age,smoking,and parity were excluded,persistent high risk HPV infection(OR 72.601;95%CI 21.48-245.42;P<0.001)was a significant independent variable for the persistence of CIN 2+in pregnancy.There was no significant correlation between age,smoking,parity and the persistence of CIN 2+in pregnancy.Conclusion:1.The progress rate of HSIL in pregnancy is low.2.Persistent infection of high-risk HPV and prenatal cytological grade≥HSIL are high-risk factors for persistent HSIL in postpartum histology.3.Colposcopic cervical biopsy at different gestational weeks,different types of high-risk HPV infection,and mode of delivery were not high-risk factors for persistent HSIL in postpartum histology.4.Pregnancy complicated with HSIL should be closely monitored during pregnancy,and spontaneous delivery can be selected.