Zhang Xiaobo, Xu Yougui, Meng Tianyu, Shen Danhua
Department of Pathology, Peking University People's Hospital, Beijing 100044, P.R. China.
Oncol Lett. 2020 Aug;20(2):1810-1816. doi: 10.3892/ol.2020.11711. Epub 2020 Jun 9.
According to the 2014 World Health Organization Classification of Tumors of Female Reproductive Organs, patients with cervical intraepithelial neoplasia 2 (CIN2) have an equivocal diagnosis, but p16 is considered as the reference index for CIN2. Positive p16 expression in CIN2 is associated with high-grade squamous intraepithelial lesions (HSIL), whereas p16 negative lesions are low-grade squamous intraepithelial lesions. The purpose of the present study was to examine the clinical value of p16 and human papillomavirus (HPV) E6/E7 mRNA in the prognostication of patients with CIN2. From January 2013 to January 2016, 108 patients were diagnosed with CIN2 by biopsy and followed up at 6-month intervals at Peking University People's Hospital (Beijing, China). The expression of HPV E6/E7 mRNA was detected by hybridization, while the expression of p16 and Ki-67 proteins was detected by immunohistochemistry. Of the 108 CIN2 cases, 20 progressed to HSIL/CIN3, 36 cases demonstrated persistence with CIN2 after the follow-up and 52 cases achieved regression (≤CIN1). Of the p16-positive 82 cases, 20 cases were detected to have progressed, whereas in the p16-negative group, no progression was observed. There were statistically significant differences among the p16-positive and negative groups (P<0.05). In the HPV E6/E7 mRNA-positive 69 cases, 18 cases were detected to have progressed, whereas in the HPV E6/E7 mRNA-negative 39 cases, progression was detected in only 2 cases. There were statistically significant differences among the HPV E6/E7 mRNA-positive and negative groups (P<0.05). The area under the receiver operating characteristics curve was plotted; the area under the curve for HPV E6/E7 mRNA was 0.745, that for p16 was 0.546 and that for Ki-67 was 0.501. The detection of HPV E6/E7 mRNA may provide important predictive information for the prognosis of CIN2, however p16 and Ki-67 proteins may provide little value.
根据2014年世界卫生组织女性生殖器官肿瘤分类,宫颈上皮内瘤变2级(CIN2)患者的诊断存在一定不确定性,但p16被视为CIN2的参考指标。CIN2中p16表达阳性与高级别鳞状上皮内病变(HSIL)相关,而p16阴性病变为低级别鳞状上皮内病变。本研究的目的是探讨p16和人乳头瘤病毒(HPV)E6/E7 mRNA在CIN2患者预后评估中的临床价值。2013年1月至2016年1月,北京大学人民医院(中国北京)对108例经活检诊断为CIN2的患者进行了随访,随访间隔为6个月。采用杂交法检测HPV E6/E7 mRNA的表达,采用免疫组织化学法检测p16和Ki-67蛋白的表达。在108例CIN2病例中,20例进展为HSIL/CIN3,36例随访后仍为CIN2,52例病变消退(≤CIN1)。在82例p16阳性病例中,20例检测到病变进展,而在p16阴性组中未观察到进展。p16阳性组和阴性组之间存在统计学显著差异(P<0.05)。在69例HPV E6/E7 mRNA阳性病例中,18例检测到病变进展,而在39例HPV E6/E7 mRNA阴性病例中,仅2例检测到病变进展。HPV E6/E7 mRNA阳性组和阴性组之间存在统计学显著差异(P<0.05)。绘制了受试者工作特征曲线下面积;HPV E6/E7 mRNA的曲线下面积为0.745,p16为0.546,Ki-67为0.501。HPV E6/E7 mRNA的检测可能为CIN2的预后提供重要的预测信息,然而p16和Ki-67蛋白可能提供的价值不大。