Study On Clinical Significance Of P16^INK4a Immunocytochemical Staining In The Management Of Cervical LSIL

Objective:By studying the positive situation of p16^INK4aimmunocytochemical staining in low-grade squamous intraepithelial lesion（LSIL）population diagnosed by colposcopy cervical biopsy,and comparing the preoperative and postoperative pathological results of cervix,to explore the screening effect of p16^INK4aimmunocytochemical staining on potential high-grade squamous intraepithelial lesion（HSIL）in LSIL patients.At the same time,a retrospective study of LSIL patients without surgical treatment was conducted to explore the relationship between the positive situation of p16^INK4aimmunocytochemical staining and high risk human papillomavirus（HR-HPV）clearance and prognosis of lesions,so as to provide basis for clinicians’management of LSIL patients.Methods:According to the inclusion and exclusion criteria,a total of 136 cases whose pathological result of cervical biopsy was LSIL（including CIN1 and CIN2 with negative immunohistochemical staining of p16）admitted to the Second Hospital of Jilin University from April 2020 to December 2021 were collected,including 80 cases in the surgery group and 56 cases in the non-surgery group.Counted the results of p16^INK4aimmunocytochemical staining and postoperative pathological results of patients in the surgery group,compared the difference of postoperative pathological results between p16^INK4aimmunocytochemical staining positive and negative patients.Counted the HR-HPV negative conversion rate at 6 months after surgery,and compared the difference of negative conversion rate of HR-HPV at 6 months after operation between patients with positive and negative p16^INK4aimmunocytochemical staining.At the same time,the negative HR-HPV status of patients in the non-surgery group after 1 year was retrospectively followed up to explore the relationship between the positive situation of p16^INK4aimmunocytochemical staining and HR-HPV clearance and prognosis of lesions after 1 year.The data were statistically analyzed by SPSS 26.0 statistical software.P<0.05 indicates that the difference is statistically significant.Results:1.The 136 patients with LSIL were divided into age<50 years old group and age≥50 years old group,there was no significant difference in the positive rate of p16^INK4aimmunocytochemical staining between the two groups（P>0.05）.There was no significant difference in the positive rate of p16^INK4aimmunocytochemical staining among the three HPV types:HR-HPV 16/18 subtype positive,HR-HPV other 12subtypes positive and mixed positive（P>0.05）.2.Among the 80 patients with LSIL in the surgery group,the postoperative pathological results were>LSIL in 4 cases and≤LSIL in 76 cases,including 33 cases of LSIL and 43 cases of chronic cervicitis.The pathological upgrading rate was5.00%.3.Among the 80 patients with LSIL in the surgery group,20 cases were positive for p16^INK4aimmunocytochemical staining,3 cases had postoperative pathological upgrading（3/20）,60 cases were negative for p16^INK4aimmunocytochemical staining,and 1 case had postoperative pathological upgrading（1/60）.The proportion of postoperative pathological upgrading in patients with positive staining of p16^INK4aimmunocytochemistry was higher than that in patients with negative staining（15.00%vs 1.67%）.The difference was statistically significant（P<0.05）.4.Taking the postoperative pathological results as the gold standard,the sensitivity of p16^INK4aimmunocytochemical staining for detecting HSIL in the population with cervical biopsy as LSIL was 75.00%,the specificity was 77.63%,the positive predictive value was 15.00%,and the negative predictive value was 98.33%.The results showed that p16^INK4aimmunocytochemical staining detection had a high negative predictive value in LSIL population.5.There was no significant difference in HR-HPV negative conversion rate 6months after surgery between p16^INK4aimmunocytochemical staining positive group and negative group（83.33%vs 90.00%,P>0.05）.The overall HR-HPV negative conversion rate of LSIL patients 6 months after surgery was 88.24%（60/68）.6.Among the 56 patients with LSIL who were followed up retrospectively without surgical treatment,the HR-HPV negative conversion rate in one year of patients with negative p16^INK4aimmunocytochemistry staining was higher than that of patients with positive staining（77.78%vs 50.00%）.The difference was statistically significant（P<0.05）.Due to the limitations of retrospective follow-up,the number of cases collected was limited.Among the patients whose HR-HPV did not turn negative after 1 year,only 3 cases with positive p16^INK4aimmunocytochemical staining underwent cervical biopsy again,but all progressed to HSIL;and only 2 cases with negative p16^INK4aimmunocytochemical staining underwent cervical biopsy again,and no pathological progression was observed.Due to limited cases,statistical analysis was not performed.7.The overall HR-HPV negative conversion rate in the surgery group at 6months after surgery was higher than that in the non-surgery group at 1 year（88.24%vs 67.86%）.The difference was statistically significant（P<0.05）.Among the patients with positive p16^INK4aimmunocytochemical staining,the HR-HPV negative conversion rate in the surgery group was higher than that in the non-surgery group（83.33%vs 50.00%）,and the difference was statistically significant（P<0.05）.Among the patients with negative p16^INK4aimmunocytochemical staining,the HR-HPV negative conversion rate in the surgery group was higher than that in the non-surgery group（90.00%vs 77.78%）,but there was no significant difference between the two groups（P>0.05）.Conclusion:1.Among LSIL patients diagnosed by cervical biopsy,the postoperative pathological upgrading rate of p16^INK4aimmunocytochemical staining positive patients was higher than that of negative patients;for patients who did not undergo surgical treatment,the rate of HR-HPV negative conversion in patients with positive staining was lower than that in patients with negative staining.Therefore,for LSIL patients with positive staining,appropriate interventions can be considered to accelerate HPV clearance,and active surgical treatment can be taken when necessary,so as to avoid missed diagnosis of high-grade lesions and prevent the continuation and further progress of lesions.2.p16^INK4aimmunocytochemical staining had a higher negative predictive value in LSIL patients diagnosed by cervical biopsy.Therefore,for LSIL patients with negative staining,relatively conservative treatment can be adopted.3.For LSIL patients,the HR-HPV negative conversion rate was higher after surgical treatment,and among patients with positive immunocytochemistry for p16^INK4a,the HR-HPV negative conversion rate was significantly higher in those who underwent surgical treatment than in those who did not.Therefore,for patients with poor compliance or heavy psychological burden and no fertility requirements,especially for patients with positive staining,surgical treatment can be considered to reduce follow-up troubles.