P16蛋白与TCT、HR-HPV的相关性及对不同子宫颈病变诊断的效能

doi:10.6040/j.issn.1671-7554.0.2021.0605

摘要/Abstract

摘要： 目的探讨P16蛋白与薄层液基细胞学(TCT)、高危型人乳头瘤病毒(HR-HPV)的相关性及对不同子宫颈病变的诊断效能差异。方法随机选取2018年7月至2020年12月就诊的1096例女性患者作为研究对象,采集患者子宫颈细胞标本,利用巴氏染色法进行TCT检测［结果分为:无恶性病变(NILM)组、意义不明(ASC-US)组、不除外高级别内瘤(ASC-H)组、低级别内瘤(LSIL)组、高级别内瘤(HSIL)组、鳞癌(SCC)组］、PCR膜杂交法进行HR-HPV检测(结果分为:HR-HPV阴性组、HR-HPV其他12亚型阳性组到HR-HPV16/18亚型阳性组)、SP二步染色法进行P16蛋白检测,探讨P16、TCT及HR-HPV的相关性。对其中272例患者进一步行阴道镜下病理活检,以病理活检结果为金标准,比较P16、TCT、HR-HPV单独和联合检测对高级别鳞状上皮内瘤(HSIL)以上病变诊断效能的差异。结果 (1) P16蛋白阳性率随着TCT诊断结果级别的升高有递增趋势(χ2 =75.17,P<0.001);ASC-US组、ASC-H组、LSIL组、HSIL 组、SCC组的P16蛋白阳性率高于NILM组,差异有统计学意义(P均<0.001);(2)P16蛋白的阳性率从HR-HPV阴性组、HR-HPV其他12亚型阳性组到HR-HPV16/18亚型阳性组,有递增趋势(χ2=137.77,P<0.001);HR-HPV16/18亚型阳性组的P16蛋白阳性率与HR-HPV其他12亚型组(χ2=12.26,P<0.001)、HR-HPV阴性组(χ2=112.77,P<0.001)相比,差异均有统计学意义;(3)P16蛋白阳性率随着子宫颈病理学诊断结果级别的升高有递增趋势(χ2=47.58,P<0.001);HSIL组、SCC组的P16蛋白阳性率均高于慢性子宫颈炎组、LSIL组,差异均有统计学意义(P均<0.001);(4)以年龄为影响因素,P16蛋白在不同子宫颈病变患者之间的表达差异有统计学意义(χ2=9.15,P=0.03);(5)联合检测法的灵敏度最高;TCT检测法的符合率最高;P16检测法的约登指数最大。结论 P16蛋白表达与TCT、HR-HPV检测结果均具有相关性;P16检测对HSIL以上病变诊断效能较高。

关键词: P16蛋白, 免疫细胞化学, 薄层液基细胞学, 高危型人乳头瘤病毒, 低/高级别鳞状上皮内病变

Abstract: Objective To investigate the correlation between P16 protein and thin-layer liquid-based cytology(TCT)and high-risk human papillomavirus(HR-HPV), and to explore its diagnostic efficacy for different cervical lesions. Methods A total of 1,096 female patients treated during July 2018 and Dec. 2020 were randomly selected as the research objects. Cervical cell samples were collected and TCT was detected by PAP staining. According to the TCT results, the patients were divided into no intraepithelial or malignant lesions(NILM)group, atypical squamous cells of unknown significance(ASC-US)group, high grade squamous intraepithelial lesions were not excluded(ASC-H)group, low grade squamous intraepithelial neoplasia(LSIL)group, high grade squamous intraepithelial neoplasia(HSIL)group and squamous cell carcinoma(SCC)group. HR-HPV was detected by hybridization capture method. According to the HR-HPV results, the patients were divided into HR-HPV negative group, HR-HPV and other 12 subtypes positive group, and HR-HPV16/18 subtypes positive group. The P16 protein was detected with SP two-step staining. The correlation between P16, TCT and HR-HPV was analyzed. Among all patients, 272 underwent colposcopic pathological biopsy, and the pathological biopsy results were taken as the gold standard to compare the diagnostic efficacies of P16, TCT and HR-HPV alone and in combination for lesions above HSIL. Results (1) The positive rate of P16 protein increased with the level of TCT diagnosis(χ2=75.17, P<0.001). The positive rate of P16 protein in ASC-US, ASC-H, LSIL, HSIL and SCC groups was significantly higher than that in NILM group(P<0.001). (2) There was a rising tendency of positive rate of P16 protein from the HR-HPV negative group, to HR-HPV and other 12 subtypes positive group and to HR-HPV 16/18 subtypes positive group(χ2=137.77, P<0.001). There was significant difference in the positive rate of P16 protein between HR-HPV 16/18 subtypes positive group and HR-HPV and other 12 subtypes positive group(χ2=12.26, P<0.001), and HR-HPV negative group(χ2=112.77, P<0.001). (3) The positive rate of P16 protein increased with the level of cervical pathological diagnosis(χ2=47.58, P<0.001). The positive rate of P16 protein in HSIL and SCC groups was significantly higher than that in chronic cervicitis LSIL group(P<0.001). (4) When age was taken as an influencing factor, there was significant difference in expression of P16 protein among patients with different cervical lesions(χ2=9.15, P=0.03). (5) The combined detection method had the highest sensitivity; TCT had the highest coincidence rate; P16 detection had the largest Youden index. Conclusion The expression of P16 protein is correlated with the results of TCT and HR-HPV; P16 detection has high diagnostic efficiency for lesions above HSIL.

Key words: P16 protein, Immunocytochemistry, Thin layer liquid based cytology, High-risk human papillomavirus, Low/high grade squamous intraepithelial neoplasia

中图分类号:

R737.11

蔡春芳,易丹妮,郭芝亮,何耀娟. P16蛋白与TCT、HR-HPV的相关性及对不同子宫颈病变诊断的效能[J]. 山东大学学报 (医学版), 2022, 60(1): 40-47.

CAI Chunfang, YI Danni, GUO Zhiliang, HE Yaojuan. Correlation between P16 protein and TCT, HR-HPV and its efficacy in the diagnosis of different cervical lesions[J]. Journal of Shandong University (Health Sciences), 2022, 60(1): 40-47.

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