P16/Ki67 dual staining versus cytology for identifying high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) in triage management of HR-HPV-positive women: a systematic review and meta-analysis.
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Abstract
Objective: The co-expression of P16 and Ki67 suggests the presence of high-grade cervical intraepithelial neoplasia, which makes P16/Ki67 dual staining a promising marker in cervical cancer screening. This study provides a systemic review of the established evidence on the performance of P16/Ki67 versus cytology in detecting cervical intraepithelial neoplasia (CIN)2+/CIN3+ among high-risk human papillomavirus (HR-HPV)-positive women and HR-HPV-positive individuals with cytology-negative results for triage management.
Methods: Studies published from database inception to April 26, 2024, were systematically searched. A total of 26 studies were eventually included in the study, comprising 26,424 women, with 14,625 classified as P16/Ki67-positive and 11,799 as P16/Ki67-negative.
Results: In the triage management of HR-HPV-positive women, P16/Ki67 achieved sensitivities of 85% for CIN2+ and 88% for CIN3+, with specificities of 63% and 57%, respectively. In comparison, cytology showed lower sensitivities of 76% for CIN2+ and 79% for CIN3+, with lower specificities of 57% and 54%. In triage management of human papillomavirus (HPV)-positive but cytology-negative women, 18.48% of the HPV-positive patients, initially missed by cytology, were correctly retrieved by the addition of P16/Ki67. A negative P16/Ki67 test result reduced the risk of underlying CIN3+ to 4% for HR-HPV-positive individuals and 1% for the HR-HPV-positive individuals with cytology-negative results, prompting a recommendation for follow-up at 1-year intervals.
Conclusion: P16/Ki67 exhibits diagnostic superiority over liquid-based cytology in detecting CIN2+/CIN3+, among HR-HPV-positive women. Furthermore, its ability to identify patients missed by cytology highlights its value as a complementary tool for triage of HR-HPV-positive but cytology-negative population. By effectively reducing unnecessary colposcopy referrals, P16/Ki67 conserves healthcare resources and improves outcomes.
期刊介绍：
The Journal of Gynecologic Oncology (JGO) is an official publication of the Asian Society of Gynecologic Oncology. Abbreviated title is ''J Gynecol Oncol''. It was launched in 1990. The JGO''s aim is to publish the highest quality manuscripts dedicated to the advancement of care of the patients with gynecologic cancer. It is an international peer-reviewed periodical journal that is published bimonthly (January, March, May, July, September, and November). Supplement numbers are at times published. The journal publishes editorials, original and review articles, correspondence, book review, etc.
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