免疫细胞化学P16/Ki-67双染、P16INK4α单染及高危型人乳头瘤病毒检测筛查高级别子宫颈病变价值比较

Comparison of values of immunocytochemical P16/Ki-67 double staining,P16^(INK4α)single staining and high-risk human papillomavirus testing in screening of high-grade cervical lesions

目的探讨免疫细胞化学P16/Ki-67双染、P16^(INK4α)单染及高危型人乳头瘤病毒(HR-HPV)检测对高级别子宫颈病变的筛查价值。方法回顾性分析2019年3月至2021年7月于太原钢铁(集团)有限公司总医院同时行子宫颈薄层液基细胞学(TCT)及HR-HPV检测的622例患者临床资料,对患者剩余细胞学标本进行P16/Ki-67双染和P16^(INK4α)单染检测。其中334例TCT结果提示为意义不明的非典型鳞状细胞(ASCUS)以上病变及HPV阳性患者行阴道镜病理活组织检查。以病理结果为参照,比较P16/Ki-67双染、P16^(INK4α)单染及HR-HPV检测筛查高级别鳞状上皮内瘤变(HSIL)及子宫颈癌的阳性预测值、灵敏度、特异度及准确度。结果以组织病理学结果为参照,结合TCT检测结果,622例患者中31例为HSIL,其中P16/Ki-67双染阳性22例(71.0%),P16^(INK4α)单染阳性23例(74.2%),HR-HPV检测阳性25例(80.6%);4例为子宫颈癌,3种检测方法阳性率均为100.0%(4/4)。622例患者中,P16/Ki-67双染、P16^(INK4α)单染及HR-HPV检测筛查出HSIL及子宫颈癌的阳性率分别为13.99%(87/622)、25.40%(158/622)、21.38%(133/622);阳性预测值分别为29.89%、17.09%、21.08%;准确度分别为91.19%、78.94%、83.28%;特异度分别为89.77%、77.98%、82.46%;灵敏度分别为74.29%、77.14%、82.86%。P16/Ki-67双染的阳性率、阳性预测值、特异度、准确度均高于P16^(INK4α)单染及HR-HPV检测,差异均有统计学意义(z值分别为-5.062和-3.418、2.328和2.450、5.436和3.570、6.043和4.161,均P<0.05);HR-HPV检测的灵敏度高于P16/Ki-67双染及P16^(INK4α)单染,但差异均无统计学意义(z值分别为-0.890、1.017,均P>0.05)。结论HR-HPV检测更适用于初次子宫颈病变筛查;P16/Ki-67双染可作为一种潜在的细胞联合筛查工具或有效的患者分流工具;P16^(INK4α)单染具有一定的局限性。

Objective To investigate the screening values of immunocytochemical P16/Ki-67 double staining,P16^(INK4α)single staining and high-risk human papillomavirus(HR-HPV)testing for high-grade cervical lesions.Methods The clinical data of 622 patients who underwent cervical thin-layer liquid-based cytology(TCT)and HR-HPV testing in General Hospital of Taiyuan Iron and Steel(Group)Co.,Ltd.from March 2019 to July 2021 were retrospectively analyzed.The remaining cytological specimens were detected by P16/Ki-67 double staining and P16^(INK4α)single staining.Among them,334 patients with TCT results suggesting atypical squamous cell of undetermined significance(ASCUS)and above and HPV-positive underwent colposcopy pathological biopsy.Using pathological results as reference,the positive predictive value,sensitivity,specificity and accuracy of P16/Ki-67 double staining,P16^(INK4α)single staining and HR-HPV testing for screening of high-grade squamous intraepithelial neoplasia(HSIL)and cervical cancer were compared.Results Taking the results of histopathology as references,combined with the results of TCT,31 of 622 patients were HSIL,of which 22(71.0%)were positive for P16/Ki-67 double staining,23(74.2%)were positive for P16^(INK4α)single staining,and 25(80.6%)were positive for HR-HPV testing;4 cases were cervical cancer,and the positive rates of the three detection methods were all 100.0%(4/4).Among 622 patients,the positive rates of P16/Ki-67 double staining,P16^(INK4α)single staining and HR-HPV testing for screening of HSIL and cervical cancer were 13.99%(87/622),25.40%(158/622)and 21.38%(133/622);the positive predictive values were 29.89%,17.09%and 21.08%;the accuracies were 91.19%,78.94%and 83.28%;the specificities were 89.77%,77.98%and 82.46%;the sensitivities were 74.29%,77.14%and 82.86%.The positive rate,positive predictive value,specificity and accuracy of P16/Ki-67 double staining were higher than those of P16^(INK4α)single staining and HR-HPV testing,and the differences were statistically significant(z values were-5.062 and-3.418,2.328 and 2.450,5.436 and 3.570,6.043 and 4.161,all P<0.05);the sensitivity of HR-HPV testing was higher than that of P16/Ki-67 double staining and P16^(INK4α)single staining,but the differences were not statistically significant(z values were-0.890 and 1.017,both P>0.05).Conclusions HR-HPV testing is more suitable for primary cervical lesion screening;P16/Ki-67 double staining can be used as a potential combined cell screening tool or an effective triage tool;P16^(INK4α)single staining has certain limitations.