p16、Ki-67表达及人乳头瘤病毒型别在子宫颈上皮内瘤变Ⅱ级治疗分流中的作用

Role of p16, Ki-67 and human papilloma virus type in the shunt treatment of cervical intraepithelial neoplasia Ⅱ

目的探讨p16、Ki-67表达及人乳头瘤病毒（HPV）型别在子宫颈上皮内瘤变Ⅱ级（CINⅡ）治疗分流中的作用。方法收集2014年1月至2016年10月在内蒙古医科大学附属医院妇产科门诊就诊、伴子宫颈高危HPV感染、经阴道镜活组织病理检查证实为CINⅡ级的337例患者存档蜡块及于该院行子宫颈环形切除术（LEEP）的病理结果。对其切片行p16、Ki-67免疫组织化学检测，并对活组织检查组织中p16、Ki-67的表达与LEEP术后的病理结果进行比较分析。对HPV型别与LEEP术后的病理结果进行比较分析。结果在337例患者中，LEEP术后病理级别分为〈CINⅡ、≥CINⅡ两组。两组患者年龄比较，差异无统计学意义（t=3.078，P=0.063）。HPV感染型别比较差异有统计学意义（χ2=12.713，P=0.005）；p16阳性表达率比较差异有统计学意义[3.6%（8/233）比88.5%（92/104）；χ2=235.54，P〈0.001]；Ki-67阳性表达率比较差异有统计学意义[3.0%（7/233）比76.9%（80/104）；χ2=197.63，P〈0.001]。p16阳性对LEEP术后≥CINⅡ的诊断灵敏度为88.89%，特异度为95.96%。Ki-67阳性对LEEP术后≥CINⅡ的诊断灵敏度为77.78%，特异度为95.80%。两组CIN患者p16、Ki-67分组类型比较，差异有统计学意义（χ2=304.28，P〈0.001）。p16＋ Ki-67＋对LEEP术后≥CINⅡ的患者诊断灵敏度为90.73%，特异度为98.74%。结论p16、Ki-67的表达可指导阴道镜活组织检查病理为CINⅡ患者的治疗，对于p16＋ Ki-67＋的CINⅡ患者应进行积极地治疗，对于p16、Ki-67单阴性或双阴性的患者可进行密切随访观察。对于伴有HPV16型感染的CINⅡ患者应进行积极的治疗。年龄不作为分流CINⅡ患者的依据。

ObjectiveTo investigate the role of p16, Ki-67 and human papilloma virus （HPV） type in the shunt treatment of cervical intraepithelial neoplasia （CIN） Ⅱ.MethodsThe paraffin block on file and the pathological results from loop electrosurgical excision procedure （LEEP） of 377 CIN Ⅱpatients diagnosed with colposcope examination accompanied by cervical high-risk HPV infection in the Affiliated Hospital of Inner Mongolia Medical University of Obstetrics and Gynecology Department from January 2014 to October 2016 were collected. The paraffin sections were stained with p16 and Ki-67 immunohistochemistry. The correlation between the expression of p16 and Ki-67 in biopsy tissues and the pathological results after LEEP was analyzed. HPV type and pathological results after LEEP were also analyzed.ResultsLEEP postoperative pathological grade in 337 cases of CINⅡ patients was divided into two groups （〈CINⅡ and ≥CINⅡ）. There was no statistical difference in age between the two groups （t = 3.078, P = 0.063）. There were statistical differences in the expressions of p16＋ and Ki-67＋ between the two groups [3.6% （8/233） vs. 88.5% （92/104）, χ2 = 235.54, P 〈 0.001; 3.0% （7/233） vs. 76.9% （80/104）, χ 2 = 197.63, P 〈 0.001]. There was a statistical difference in HPV infection type between the two groups （χ 2 = 12.713, P = 0.005）. The sensitivity and specificity of p16＋ and Ki-67＋ for LEEP postoperative≥CINⅡ was 88.89% vs.77.78% and 95.96% vs. 95.80% respectively. There was a statistical difference in group type of p16 and Ki-67 in both groups （χ 2 = 304.28, P 〈 0.001）. The sensitivity of p16＋ Ki-67＋ was 90.73% and the specificity was 98.74% in CINⅡ patients for LEEP postoperative.ConclusionsThe expressions of p16 and Ki-67 can guide the colposcopic biopsy for the treatment of CINⅡ. For CINⅡ patients with p16＋ Ki-67＋, the active treatment should be taken. Close observation needs to follow for p16 and Ki-67 single negative or double negative patients. Active treatment should be performed for CINⅡ patients with HPV16 type infection in CINII. Age can not be used as the basis for the patients with shunt CINⅡ.