Abstract
Background
Studies on the clinical performance of p16/Ki-67 dual-staining in detecting cervical lesions by menopausal status were limited.
Methods
4364 eligible women were enrolled with valid p16/Ki-67, HR-HPV, and LBC test results, including 542 cancer and 217 CIN2/3 cases. The positivity rates of p16 and Ki-67 single staining and p16/ Ki-67 dual-staining were analyzed by different pathological grades and age groups. The sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV) of each test in different subgroups were calculated and compared.
Results
P16/Ki-67 dual-staining positivity increased with histopathological severity in premenopausal and postmenopausal women (P < 0.05), while no increasing trends of individual expression of p16 single staining and Ki-67 single staining were observed in postmenopausal women. P16/Ki-67 showed higher SPE (88.09% vs. 81.91%, P < 0.001) and PPV (33.8% vs. 13.18%, P < 0.001) in detecting CIN2/3, and higher SEN (89.97% vs. 82.61%, P = 0.012) and SPE (83.22% vs. 79.89%, P = 0.011) in detecting cancer in premenopausal women than postmenopausal women. For triaging the HR-HPV+ population to identify CIN2/3, p16/Ki-67 performed comparably to LBC in the premenopausal women, and showed higher PPV (51.14% vs. 23.08%, P < 0.001) in premenopausal than postmenopausal women. For triaging ASC-US/LSIL population, p16/Ki-67 demonstrated higher SPE and lower colposcopy referral rate than HR-HPV in both premenopausal and postmenopausal women.
Conclusions
Expressions of p16/Ki-67 dual-staining between premenopausal and postmenopausal women are varied. P16/Ki-67 performs better in detecting cervical lesions in premenopausal women. For triaging, p16/Ki-67 is suitable for HR-HPV+ women, especially premenopausal women, to identify CIN2/3 and women with ASC-US/LSIL.
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Data availability
Data that support the findings of this study are available in the article.
Abbreviations
- HR-HPV:
-
High-risk human papillomavirus
- LBC:
-
Liquid-based cytology
- NILM:
-
Negative for intraepithelial lesion or malignancy
- ASC-US:
-
Atypical squamous cells of undetermined significance
- AGC:
-
Atypical glandular cells
- LSIL:
-
Low-grade squamous intraepithelial lesion
- HSIL:
-
High-grade squamous intraepithelial lesion
- ASC-H:
-
Atypical squamous cells-cannot exclude HSIL
- SCC:
-
Squamous cell carcinoma
- AIS:
-
Adenocarcinoma in situ
- ADC:
-
Adenocarcinoma
- CIN:
-
Cervical intraepithelial neoplasia
- SEN:
-
Sensitivity
- SPE:
-
Specificity
- PPV:
-
Positive predictive value
- NPV:
-
Negative predictive value
- CI:
-
Confidence interval
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Acknowledgements
We thank all the patients who generously accepted to participate in this study. COBAS and COBAS E are trademarks of Roche.
Funding
This work was funded by CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-004), National Natural Science Foundation of China (81973136), Sichuan Provincial Science and Technology Program Applied Basic Research Program (2021YJ0227), and Roche Diagnostics (Shanghai) Limited.
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Study concepts and Study design: YD, WC, and JY; data collection: YD, WC, TC, TL, YZ, YW, and SC; quality control of data and algorithms: TL, XL, CZ, and WC; data analysis, interpretation and statistical analysis: YD; investigation, TL, ZW, LY, and MJ; Manuscript preparation: YD; manuscript editing: YD and WC; manuscript review: WC; all authors reviewed and approved the final manuscript.
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Dai, Y., Chen, T., Li, X. et al. Evaluation of the clinical performance of p16/Ki-67 dual-staining cytology for cervical lesion detection in premenopausal and postmenopausal Chinese women. J Cancer Res Clin Oncol 149, 10645–10658 (2023). https://doi.org/10.1007/s00432-023-04938-1
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DOI: https://doi.org/10.1007/s00432-023-04938-1