Risk Factors Of Persistent HR-HPV Infection After Treatment With Negative Surgical Margins For High-grade Squamous Intraepithelial Lesion

Background:Cervical cancer is the terminal stage of a series of clinically defined lesions occurring in the cervical epithelium,whose occurrence and development are closely related to cervical intraepithelial neoplasia.The diagnosis and treatment of cervical intraepithelial neoplasia,especially high-grade intraepithelial lesions,is of vital significance for the control of disease progression and the prevention of cervical cancer.Currently,both European and American guidelines recommend conization as the preferred treatment for HSIL.To a certain extent,conization plays a role in the removal of SIL lesions and the clearance of HPV virus.However,even after treatment,there are still 10%-53%of women with persistent or recurrent disease,and the risk of long-term development of cervical cancer is still 4-5 times higher than that of normal people.Because of the potential risk,follow-up after surgical treatment is of extreme importance.Related studies suggested that long-term persistent HR-HPV infection is a precursor to the occurrence of CIN and an independent risk factor for recurrence after conization.Although there is no unified definition of HPV persistent infection,most scholars believe that HPV positive detected at least2 time nodes is HPV persistent infection.Therefore exploring the relevant risk factors of persistent HR-HPV infection will play a positive role in guidance of clinical work.Recently,the positive margins after conization have received clinical attentions,while the negative margins have not.Several studies reported that even for patients with negative margins,the postoperative recurrence rate is still as high as 2-10.5%,and it is even found that the lesion has progressed to cervical cancer during follow-up.Generally,it is one of the hot issues to be solved to detect the risk factors of persistent HR-HPV infection after treatment with negative surgical margins for high-grade squamous,reduce the postoperative HR-HPV infection rate,implement effective postoperative management,and carry out reasonable shunt.Objective:(1)To understand the distribution of HR-HPV in the population with negative surgerical margins after HSIL treatment;(2)To explore the risk factors associated with persistent positive HR-HPV infection after treatment with negative surgical margins for high-grade squamous,and the outcome of 2 years of follow-up,summarize experience and guide clinical diagnosis and treatment.Methods:According to the inclusion and exclusion criteria,112 cases of negative surgical margins for HSIL were selected from the Second Hospital of Jilin University from January 2018 to October 2020.Relevant data were gathered,including age,smoking history,menstrual history,history of pregnancy and birth,initial load of HPV virus,initial type of HPV virus,surgical means,pathological data and other factors that may have an impact on the residual lesions.In accordance with the statue of HPV after the operation,they were divided into the persistent positive group,the transient infection group and the turning negative group.General data and clinical data were compared and analyzed to screen out independent risk factors by the chi-square test and Logistic regression analysis.All cases were followed up for at least18 months after surgery.HPV testing and TCT testing were performed at 6 months,12 months,18 months,and 24 months after surgery,and ECC and colposcopy biopsy were operated if it is necessary.Results:(1)Among the 112 patients with negative surgical margins for HSIL.28 patients were continuously positive,36 patients were transient infected,and48 patients were negative during 2 years of follow-up,with a continuous positive rate of 25%.(2)General information of the included cases: 1)Age: there were significant differences in average age among the three group.the age of the persistent positive group was higher than that of the transient infection group,and the difference between the two groups was statistically significant(P=0.008 < 0.05).2)Adverse chief complaints: The number of cases with adverse chief complaints including contact bleeding and irregular vaginal bleeding in the persistent positive group was higher than that in the transient infection group and the transnegative group,the difference was statistically significant(P=0.042 < 0.05,P=0.000 < 0.05).While there was no statistically significant difference between the transient infection group and the transnegative group.3)There were no significant differences in menopause,smoking,number of vaginal deliveries and abortion,and placement of intrauterine device among the three groups(P>0.05).(3)Clinical data : 1)Type of cervical transformation zone under colposcopy before the first surgical treatment: The difference among the three groups was statistically significant(P=0.037< 0.05).In pair comparison,the difference of the type of transformation zone between the persistent positive group and the negative group was also statistically significant(P=0.016 < 0.05).2)The lesions involved in the multiquadrant under colposcopy before the first treatment:The differences between the persistent positive group and the negative group,and between the transient infection group and the negative group were statistically significant(P=0.005 < 0.05,P=0.014 < 0.05),while there was no significant difference between the continuous positive group and the transient group.3)The lesion range under colpososcopy(iodine non-staining area)before the first treatment:The lesion range was larger in the persistent positive group than that of the negative group,and larger in the transient infection group than that of the negative group,with statistically significant differences(P=0.001<0.05,P=0.011<0.05).There was no statistically significant difference between the persistent positive group and the transient group.4)There were no significant differences in initial HPV viral load,HPV viral type,lesion involvement in the gland,and surgical means(CKC and LEEP)among the three groups(P>0.05).(4)Mulariate analysis showed that the adverse chief complaint(including contact bleeding and irregular vaginal bleeding)and the extent of lesions under colpopharoscopy before the first surgical treatment were independent related factors for persistent HR-HPV infection after treatment with negative surgical margins for HSIL.(5)21 of the 112 patients were positive for TCT during 2 years of follow-up,with a positive rate of TCT of 18.75%.Comparison of the number of TCT positive cases in the three groups showed statistical significance(P=0.007<0.05).There were 22 patients with recurrence within 2 years,with a recurrence rate of 19.64%.The difference in the number of cases of recurrence among the three groups was statistically significant(P<0.001).Conclusion:(1)The continuous positive rate of HR-HPV in HSIL patients with negative surgical margin was 25%.Moreover the positive rate of TCT and the recurrence rate of lesions significantly increased within 2 years,suggesting that long-term follow-up of this population should not be ignored.(2)The adverse chief complaint(contact bleeding,irregular vaginal bleeding)and the scope of involvement of colpopharyngeal lesions before the first surgical treatment are independent related factors for persistent HR-HPV infection in HSIL patients with negative surgical margin.It is necessary to strengthen postoperative follow-up and appropriately extend follow-up time for patients with one of these two factors.(3)Initial HPV viral load,HPV viral type,and surgical means(CKC and LEEP)were not associated with persistent HR-HPV infection in patients with negative surgical margins for HSIL.