Evaluation on cervical intraepithelial neoplasia for patients with cervicitis by p16/Ki-67 double staining

doi:10.3877/cma.j.issn.1674-1358.2022.06.009

Abstract

Abstract:

Objective

To investigate the diagnostic value of p16/Ki-67 double staining based on cell block technology for cervical intraepithelial neoplasia (CIN) higher than grade 2 (≥ CIN2) for patients with atypical squamous cells of undetermined significance (ASC-US)/low-grade squamous intraepithelial lesions (LSIL).

Methods

From January 2021 to December 2021, a total of 222 patients with cervicitis who underwent colposcopy biopsy, DNA ploidy analysis and high risk human papillomarirus (HR-HPV) testing were selected from Beijing Haidian Maternal and Child Health Hospital. Cytological results of all cases were ASC-US/LSIL. The remaining liquid based cytology (LBC) specimens of patients were stained with p16/Ki-67 double staining based on cell block technology, and the diagnostic value of p16/Ki-67 double staining compared with DNA ploidy analysis and HR-HPV for ≥ CIN2 lesions were analyzed by receiver operating characteristic curve (ROC).

Results

The Kappa value of p16/Ki-67 double staining in cell block was 0.835, which was highly consistent with the pathological diagnosis of biopsy. The area under ROC (AUC) of p16/Ki-67 double staining was 0.900 (the specificity and sensitivity were 94.16% and 85.45%, respectively), which was significantly higher than that of HR-HPV testing (AUC was 0.557, with the specificity and sensitivity were 13.17% and 98.18%, respectively) (Z = 11.387, P < 0.001) and DNA ploidy analysis (AUC was 0.583, with the specificity and sensitivity were 32.93% and 83.64%, respectively) (Z = 7.476, P < 0.001), with significant differences. Compared with HR-HPV testing and DNA ploidy analysis, the NRI values of p16/Ki-67 double staining were 1.470 (95%CI: 1.246-1.470, P < 0.001) and 1.278 (95%CI: 1.049-1.278, P < 0.001), respectively. The IDI values were 0.609 (95%CI: 0.525-0.692, P < 0.001) and 0.633 (95%CI: 0.554-0.713, P < 0.001), respectively.

Conclusions

The p16/Ki-67 double staining based on cell block has a better predictive ability for the correct classification of patients ≥ CIN2, and is a good method for the triage of patients with ASC-US/LSIL, which can effectively avoid the over-diagnosis and treatment.

Key words: Cervical cancer screening, p16/Ki-67 double staining, Atypical squamous cells of undetermined significance, Low-grade squamous intraepithelial leasion, Cell block, Cervical intraepithelial neoplasia

Xiaofei Sun, Yiqun Gu, Aichun Wang, Li Wang, Fanfan Meng, Jun Wang, lijuan Lu. Evaluation on cervical intraepithelial neoplasia for patients with cervicitis by p16/Ki-67 double staining[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2022, 16(06): 418-425.

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References 34

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筛查方法	病理诊断		Kappa值
筛查方法	阳性（≥ CIN2）（n = 58）	阴性（< CIN2）（n = 164）	Kappa值
HR-HPV阳性	57（98.28）	142（86.59）	0.065
DNA倍体阳性	49（84.48）	109（66.46）	0.116
细胞块p16/Ki-67双染阳性	50（86.21）	6（3.66）	0.835

筛查方法	病理诊断		Kappa值
筛查方法	阳性（≥ CIN2）（n = 58）	阴性（< CIN2）（n = 164）	Kappa值
HR-HPV阳性	57（98.28）	142（86.59）	0.065
DNA倍体阳性	49（84.48）	109（66.46）	0.116
细胞块p16/Ki-67双染阳性	50（86.21）	6（3.66）	0.835

诊断方法	敏感度（%）	特异度（%）	AUC（95%CI）	DeLong’s test^a
诊断方法	敏感度（%）	特异度（%）	AUC（95%CI）	Z值	P值
细胞块p16/Ki-67双染	85.45	94.61	0.900（0.841~0.958）	—	—
HR-HPV检测	98.18	13.17	0.557（0.474~0.640）	11.387	< 0.001
DNA倍体分析	83.64	32.93	0.583（0.500~0.666）	7.476	< 0.001

诊断方法	敏感度（%）	特异度（%）	AUC（95%CI）	DeLong’s test^a
诊断方法	敏感度（%）	特异度（%）	AUC（95%CI）	Z值	P值
细胞块p16/Ki-67双染	85.45	94.61	0.900（0.841~0.958）	—	—
HR-HPV检测	98.18	13.17	0.557（0.474~0.640）	11.387	< 0.001
DNA倍体分析	83.64	32.93	0.583（0.500~0.666）	7.476	< 0.001

方法比较	IDI（95%CI）	NRI（95%CI）	NRI（+）（95%CI）	NRI（－）（95%CI）
P16/Ki67 vs. HR-HPV	0.609（0.525~0.692）	1.470（1.246~1.470）	0.709（0.500~0.709）	0.760（0.673~0.760）
P16/Ki67 vs. DNA倍体	0.633（0.554~0.713）	1.278（1.049~1.278）	0.709（0.510~0.889）	0.569（0.485~0.657）

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