p16/Ki-67双染对比液基细胞学及HPV DNA检测在宫颈癌早期筛查中的价值

Value of p 16/Ki-67 dual staining contrast liquid-based cytology and HPV DNA detection in early screening for cervical cancer

目的:液基细胞学(liquid-based cytology,LBC)及高危型人乳头瘤病毒(human papilloma virus,HPV)DNA检测在宫颈早期病变筛查中具有重要意义,但在临床检测过程中也凸显出一些不足。p16/Ki-67双染是一种新兴的检测方法。本研究探讨p16/Ki-67双染检测对比LBC及HPV DNA检测在宫颈早期病变筛查中的特点。方法:选取2021年7月至2023年7月郑州市妇幼保健院妇科收治的组织学证实为慢性宫颈炎、低度鳞状上皮内病变(low-grade squamous intraepithelial lesion,LSIL)、高度鳞状上皮内病变(high-grade squamous intraepithelial lesion,HSIL)及以上且均进行LBC、HPV DNA、p16/Ki-67双染检测的292例患者作为研究对象。所有患者以组织病理学诊断为金标准,分析p16/Ki-67双染检测在不同活体组织检查(以下简称“活检”)分级中的差异和在LBC异常结果以及HPV DNA检测阳性和LBC阴性样本中的分流作用,分析LBC、HPV DNA、p16/Ki-67双染检测在宫颈病变中的诊断效能并进行受试者操作特征(receiver operator characteristic,ROC)曲线的效果评价。结果:LBC检出的无上皮内病变或恶性病变(negative for intraepithelial lesion or malignancy,NILM)与活检结果符合率为67.6%(119/176),意义不明确的非典型鳞状细胞(atypical squamous cells of undetermined significance,ASC-US)中有26.7%(20/75)患者活检阴性,LSIL及以上病变中有22.0%(9/41)患者活检阴性。HPV DNA检测阳性(包括单独HPV DNA检测阳性及合并LBC、p16/Ki-67双染阳性)患者中60.5%(135/223)活检为LSIL和HSIL,39.5%(88/223)活检为阴性。p16/Ki-67双染阳性患者中,70.4%(112/159)活检为LSIL和HSIL,29.6%(47/159)活检为阴性。3种检测方法中,p16/Ki-67双染与活检符合率最高,为72.9%(213/292)。对于LSIL及以上病变,HPV DNA检测灵敏度最高,为93.8%;LBC特异度最高,为80.4%,而3种方法两两联合筛查之间结果差异无统计学意义(均P>0.05)。p16/Ki-67双染对HPV DNA检测阳性标本比LBC更具有指导意义;p16/Ki-67双染在LBC真阴性标本中比HPV DNA检测更具优势;而对于HPV DNA检测阳性而LBC检测阴性的标本,p16/Ki-67双染差异也有统计学意义(P<0.05)。结论:p16/Ki-67阳性率与宫颈病变严重程度相关;p16/Ki-67联合LBC或HPV DNA检测可有效提高LBC和HPV结果不一致时的准确性。

Objective:Liquid-based cytology(LBC)and human papilloma virus(HPV)DNA detection have important significance in early screening for cervical lesions,but they exhibit some limitations in clinical practice.p16/Ki-67 dual staining is an emerging detection method.This study explores the characteristics of p16/Ki-67 dual staining detection compared to LBC and HPV DNA detection in early screening for cervical lesions.Methods:A total of 292 patients diagnosed with chronic cervicitis,low-grade squamous intraepithelial lesion(LSIL),high-grade squamous intraepithelial lesion(HSIL)and above(HSIL+),confirmed by histology and undergoing LBC,HPV DNA detection,and p16/Ki-67 dual staining tests from July 2021 to July 2023 at the Maternal and Child Health Care Hospital of Zhengzhou were selected as the research subjects.Histopathology served as the gold standard for diagnosis.The differences in p16/Ki-67 dual staining among different biopsy grades and its triage in abnormal LBC results,HPV DNA detection-positive,and LBC-negative samples were analyzed.The diagnostic efficacy of the 3 methods in cervical lesions was compared and the receiver operator characteristic(ROC)curve was evaluated.Results:The concordance rate between intraepithelial lesion or malignancy(NILM)detected by LBC and biopsy results was 67.6%(119/176).Among patients with atypical squamous cells of undetermined significance(ASC-US),26.7%(20/75)had negative biopsies,and among LSIL and above lesions,22.0%(9/41)had negative biopsies.In HPV DNA detection-positive patients(including single HPV DNA detection-positive and combined LBC and p16/Ki-67 dual staining-positive),60.5%(135/223)had biopsies indicating LSIL and HSIL,while 39.5%(88/223)had negative biopsies.Among p16/Ki-67 dual staining-positive patients,70.4%(112/159)had biopsies indicating LSIL and HSIL,and 29.6%(47/159)had negative biopsies.Among the 3 detection methods,p15/Ki-67 dual staining had the highest concordance rate with biopsy results at 72.9%(213/292).For LSIL and above lesions,HPV DNA detection had the highest sensitivity at 93.8%,LBC had the highest specificity at 80.4%,and there was no statistically significant difference between the 3 methods of pairwise combined screening(all P>0.05).p16/Ki-67 dual staining had more guiding significance for true positive HPV DNA detection specimens than LBC;it had an advantage over HPV DNA detection in true negative LBC specimens,and there was also a statistically significant difference for specimens that were HPV DNA detection-positive but LBC-negative(P<0.05).Conclusion:The positive rate of p16/Ki-67 dual staining is correlated with the severity of cervical lesions.The combination of p16/Ki-67 dual staining with LBC or HPV DNA detection can effectively improve diagnostic accuracy when LBC and HPV DNA detection results are inconsistent.