【摘要】 背景与目的:目前,临床上仍缺乏对宫颈细胞学阴性且高危型人乳头状瘤病毒(high-risk human papilloma virus,HR-HPV)阳性病例的有效分流措施,同时预测组织学为低度鳞状上皮内病变(low-grade squamous intraepithelial lesion,LSIL)的病例是否会进展为宫颈高度病变的生物学指标尚不明确。探讨免疫细胞化学p16/Ki-67双染检测对宫颈细胞学阴性且HRHPV阳性病例的分流作用及LSIL的转归预测价值。方法:收集2017年4月—2018年7月于汕头市中心医院和中山大学肿瘤防治中心就诊、宫颈癌筛查细胞学阴性且HR-HPV阳性、30岁以上的708例已婚女性患者为研究对象。患者均进行了初次阴道镜检查和p16/Ki-67双染检测,观察p16/Ki-67双染检测结果与初次阴道镜组织学结果之间的关系,探讨p16/Ki-67双染诊断宫颈上皮内瘤变2/3级(cervical intraepithelial neoplasia 2/3,CIN2/CIN3)的效能,比较p16/Ki-67双染检测阳性率在不同亚型HPV感染组之间的差异。并对初次阴道镜组织学LSIL的223例患者随访1年,分析p16/Ki-67双染检测结果对LSIL转归的预测价值。结果:在生物显微镜下,宫颈细胞p16/Ki-67双染检测结果分为阴性和阳性两类。p16/Ki-67双染阳性患者中CIN2+的发生率[33.33%(55/165)]与p16/Ki-67双染阴性患者中CIN2+的发生率[1.10%(6/543)]相比差异有统计学意义(χ2=166.94,P<0.001)。p16/Ki-67双染阳性患者中CIN3+的发生率[26.06%(43/165)]与p16/Ki-67双染阴性患者中CIN3+的发生率[0.37%(2/543)]相比差异有统计学意义(χ2=140.35,P<0.001)。HPV其他12亚型组、HPV16/18亚型组、同时阳性组对应的p16/Ki-67双染阳性率变化经χ2趋势检验分析得知有递增趋势(χ2=29.119,P<0.001)。三组间两两比较,p16/Ki-67双染阳性率之间差异有统计学意义(P<0.01)。8例LSIL病变进展的患者中,有6例p16/Ki-67双染阳性,2例p16/Ki-67双染阴性,p16/Ki-67双染阳性诊断LSIL病变进展率是p16/Ki-67双染阴性的3倍。22例LSIL病变持续的患者中,有12例p16/Ki-67双染阳性,10例p16/Ki-67双染阴性,p16/Ki-67双染阳性诊断LSIL病变持续率是p16/Ki-67双染阴性的1.2倍。29例LSIL病变消退的患者中,有3例p16/Ki-67双染阳性,26例p16/Ki-67双染阴性,p16/Ki-67双染阳性诊断LSIL病变消退率是p16/Ki-67双染阴性的3/26。结论:p16/Ki-67双染检测对诊断CIN2/CIN3具有较高的效能,其阳性率与高危型HPV感染亚型有关,是分流宫颈细胞学阴性且HR-HPV阳性患者的有效方法,对组织LSIL的转归也具有较高的预测价值,有望临床推广使用。更多还原

【Abstract】 Background and purpose: At present, there is a lack of effective shunt measures for the patients with negative cervical cytology and positive high-risk human papilloma virus(HR-HPV). At the same time, it is not clear whether the patients with low-grade squamous intraepithelial lesion(LSIL) will progress to high-grade cervical lesions. The purpose of this study was to explore the role of immunocytochemical p16/Ki-67 double staining in the shunt of cervical cytology negative and HR-HPV positive patients and the predictive value of LSIL outcome. Methods: From Apr. 2017 to Jul. 2018, 708 married women over the age of 30 were selected from Shantou Central Hospital and Sun Yat-sen University Cancer Center. Cervical cancer screening was negative, and HR-HPV was positive in those women. All patients underwent primary colposcopy and p16/Ki-67 double staining. The relationship between the results of p16/Ki-67 double staining and the histological results of primary colposcopy was observed. The efficacy of p16/Ki-67 double staining in the diagnosis of cervical intraepithelial neoplasia grade 2/3(CIN2/CIN3) was discussed. The difference in the positive rate of p16/Ki-67 double staining between different HPV subtype infection groups was compared. Two hundred and twenty-three patients with LSIL were followed up for one year. The predictive value of p16/Ki-67 double staining test results for the outcome of LSIL was analyzed. Results: Under biomicroscopy, the results of double staining of p16/Ki-67 in cervical cells were divided into two categories: negative and positive. The incidence of CIN2+ was 33.33%(55/165) in the patients with positive double staining of p16/Ki-67 and 1.10%(6/543) in the patients with negative double staining of p16/Ki-67(χ2=166.94,P<0.001).The incidence of CIN3+ was 26.06%(43/165) in patients with positive double staining of p16/Ki-67 and 0.37%(2/543) in patients with negative double staining of p16/Ki-67(χ2=140.35,P<0.001). χ2 trend test showed the positive rate of p16/Ki-67 in the other 12 subtypes of HPV, 16/18 subtypes of HPV and the simultaneous positive group was increased(χ2=29.119, P<0.001). The positive rates of p16/Ki-67 double staining were significantly different among the three groups(P<0.01). Among 8 cases of LSIL with progressive disease, 6 cases were positive for p16/Ki-67, and 2 cases were negative for p16/Ki-67. The positive rate of p16/Ki-67 double staining was 3 times higher than the negative rate of p16/Ki-67 double staining. Among 22 cases of LSIL with persistent disease, 12 cases were positive for p16/Ki-67, and 10 cases were negative for p16/Ki-67. The persistence rate of p16/Ki-67 double staining positive diagnosis of LSIL was 1.2 times that of p16/Ki-67 double staining negative diagnosis. Among 29 patients with regression of LSIL, 3 were positive for p16/Ki-67, and 26 were negative for 16/Ki-67. The regression rate of p16/Ki-67 double staining positive diagnosis of LSIL was 0.12 times that of p16/Ki-67 double staining negative diagnosis. Conclusion: p16/Ki-67 double staining test has high efficiency in the diagnosis of CIN2/CIN3. The positive rate of p16/Ki-67 double staining test is related to high-risk HPV infection subtypes. p16/Ki-67 double staining test is an effective method for cases with negative cervical cytology and positive HR-HPV. It has high predictive value for the prognosis of tissue LSIL and potential for clinical application.更多还原