宫颈锥切切缘阳性患者残留或复发的危险因素及再处理分析

Risk factors of persistent and recurrent lesions and re-treatment for positive margin after cold-knife conization

目的通过回顾性分析宫颈初次锥切后切缘阳性病例,明确相关危险因素对病变残留和复发的影响,为此类患者的后续治疗和随访策略提供依据。方法 2006年1月至2016年12月因CIN2及以上高级别病变于北京大学人民医院住院宫颈冷刀锥切术患者,宫颈锥切切缘阳性的病理分级提示为CIN2者需重新阅片、调取相应病理组织蜡块重新切片,进行P16的免疫组化染色并判读,对结果进行相应分析。结果 85例锥切切缘病理诊断均为HSIL及以上病变,发现有病变残留或复发者33例（38.8%）,未发现者52例。对锥切切缘阳性的CIN患者病变复发或残留影响因素的差异进行单因素分析。术后HPV持续阳性、切缘位置、产次等变量单因素分析差异有统计学意义（P〈0.05）,行多因素分析结果显示,产次≥2次的锥切切缘阳性的CIN患者病变残留或复发的风险更高（P〈0.05）;术后HPV阳性和锥切标本内外切缘均为阳性亦提示CIN病变残留或复发高危。术后以p16染色情况作为提示病变残留或复发的指标,则可计算其敏感性为80%,特异性为91%,阳性预测值0.89,阴性预测值0.83。年龄（P〈0.001）、病变级别（P=0.042）、产次（P=0.009）、绝经状态（P=0.010）,再手术治疗病变残留及复发者所占比例更大（P〈0.001）。结论多产,内、外切缘均阳性,切缘阳性的病变级别高,持续HPV感染,是宫颈锥切切缘阳性患者病变残留或复发的高危因素;p16免疫组化染色阳性可用作锥切阳性患者术后病变残留或复发的阳性预测较为特异的指标。

Objective To investigate the risk factors and re-treatment strategies of residual and recurrent high-grade squamous intraepithelial Lesion（HSIL） in patients whose pathology results of primary cold-knife conizations were positive margin,and to provide evidence for clinical decisions. Methods 85 patients who were diagnosed as HSIL from Jan 2006 to Dec 2016 by pre-operative colposcopy and biopsy of cervix received the primary cold-knife conization（CKC） and follow-up in Peking University People＇s Hospital. P16 immunohistochemistry method was applied to learn more about the margin of CIN2 and the assessment of the lesions. Results Those 85 cases were all diagnosed as HSIL or higher grades of lesions. The rate of persistent and recurrent lesions was 38.8%（33/85）. Single factor analysis was performed on the difference of factors influencing the recurrence or residual of CIN in patients with positive margin. There were statistically significant differences in postoperative analysis of HPV status, position of incision margin, and parity（P〈0.05）. Multivariate analysis showed that CIN patients with positive margin of two or more deliveries had a higher risk of residual or recurrence of lesions（P〈0.05）. Both HPV positive and the positive of internal and external margin of specimen suggested a high risk of residual or recurrence. p16 staining can be used to indicate residual or recurrence of lesions, and its sensitivity was 80%, specificity was 91%, positive predictive value was 0.89 and negative predictive value was 0.83. Age（P〈0.001）, the grade of lesion（P=0.042）, number of births（P=0.009）, postmenopausal status（P=0.010）, for these people, the proportion of patients with residual and recurrent lesions treated by reoperation was higher（P〈0.001. Conclusions Patients has both positive endomargin and ectomargin, more times of parity and positive HPV load after operation indicated higher risk of persistence and recurrence of CIN. Positive immunohistochemical staining of p16 can be used as a relatively specific indicator for the residual or recurrence of lesions in patients with positive margin after cold-knife conization.