Analysis Of The Factors Of Prognosis In Women Of Childbearing Age With Negative Margin After Conization For Cervical High-Grade Squamous Intraepithelial Lesion

Objective: To identify factors for predicting high-risk human papillomavirus（HR-HPV）persistence and lesion residual or recurrence after cervical conization with negative margins in childbearing age women diagnosed as cervical high-grade squamous intraepithelial lesions（HSIL）,so as to provide a theoretical basis for formulating individualized postoperative management strategies which can improve their prognosis and reduce their risk of adverse pregnancy outcomes.Methods: Childbearing age women diagnosed as HSIL underwent cold knife conization（CKC）with negative margin at the Affiliated Hospital of Jining Medical College between January 2017 and December 2018 were participated in our study.All patients were preoperatively HR-HPV positive and underwent HPV testing and/or Thinprep cytologic test（TCT）at 3,6 and 12 months after conization.The effects of age,pregnancy history,conization depth,preoperative HPV genotype,glandular involvement,use of intrauterine device（IUD）and postoperative adjuvant therapy on HR-HPV persistence and residual or recurrence were analyzed retrospectively.Results: 365 patients were included,244（66.85%）of whom infected HPV16 prior to conization.The HR-HPV persistence rates were 23.01%,15.07%and 9.86% at 3,6 and 12 months after conization,respectively.Twenty residual or recurrent cases（5.48%）were identified within 24 months of follow-up.Univariate analysis showed that pregnancy history,glandular involvement,IUD use,conization depth and preoperative HPV16 infection were not significantly associated with HR-HPV persistence after CKC in patients with HSIL（P>0.05）.Age was associated with HR-HPV persistence for 6 and 12 months（P=0.009,P=0.001）;postoperative adjuvant therapy was associated with HR-HPV persistence for 12 months（P=0.032）.Multivariate analysis showed that age was the only significant independent risk factor of HR-HPV persistence for 12months（P=0.012,OR=13.116）and postoperative adjuvant therapy was a protective factor（P=0.040,OR=0.476）.In univariate analysis,Age,preoperative HPV16 infection,IUD use,conization depth and pregnancy history were not related to residue or recurrence after CKC in patients with HSIL（P>0.05）.HR-HPV persistence for 3 months or more and glandular involvement were significantly related to residual or recurrent（P<0.05）.Follow-up at 12 months revealed that recurrence rate was higher when patients were persistent HPV16 infection rather than other HR-HPV after conization（P=0.034）.In multivariate analysis,HR-HPV persistence was independent risk factor for residual or recurrent.The odds ratios in patients with persistent HRHPV infection increased gradually from 22.082 at 3-month follow-up visit to29.291 and 44.025 at 6-and 12-month follow-up visits,respectively.Smooth curve fitting showed that the risk of HR-HPV persistence and residual or recurrence had a tendency to rise in patients older than 30 years.Conclusion: Age is an independent risk factor for persistent HR-HPV infection for 6 months or more in women of reproductive age after HSIL conization with negative margin and postoperative adjuvant therapy can accelerate the clearance of HR-HPV.The risk of residual or recurrence is significantly associated with persistent HR-HPV infection for 3 months or more and is positively correlated with the duration of persistent infection.HPV16 persistence has a higher risk of recurrence than other HR-HPV.For women older than 30 years,especially those with HPV16 persistence after HSIL conization,postoperative management should be strengthened and adjuvant therapy such as immunotherapy and antiviral drug therapy should be actively used to achieve better treatment outcomes,regardless of marginal status.