Application of P16 /Ki‐67 dual‐staining for the detection of high‐grade cervical lesions in the triage of patients with minor abnormal cytology: A meta‐analysis
Abstract
Background
The p16/Ki‐67 dual‐staining is increasingly applied to increase diagnostic accuracy in detecting high‐grade cervical lesions, including cervical intraepithelial neoplasia Grade 2 (CIN2+) and CIN3+.
Objectives
To compare the diagnostic performance of p16/Ki‐67 dual‐staining with the human papillomavirus (HPV) tests in the triage of women with atypical squamous cells of undetermined significance (ASC‐US) and low‐grade squamous intraepithelial lesions (LSIL) cytology results.
Search Strategy
Publications before April 27, 2024, were identified through PubMed, Embase, Web of Science, and Cochrane Library.
Selection Criteria
The studies have head‐to‐head comparison of p16/Ki‐67 dual‐staining and HPV testing in detecting high‐grade cervical lesions.
Data Collection and Analysis
Two researchers independently screened articles by title, abstract, and full text. The GRADE and QUADAS‐2 tool was used for quality evaluation. The pooled sensitivity and specificity for CIN2+ and CIN3+ were estimated using random effects models, with results and heterogeneity assessments presented in forest plots. Pretest‐posttest probability (PPP) plots were constructed to evaluate the detection rates of CIN3+ in ASC‐US and LSIL patients.
Main Results
Twenty‐one studies with 6394 participants were included. The pooled specificity of p16/Ki‐67 dual‐staining was higher than that of HPV tests (CIN2+: 0.73 [95% confidence interval [CI] 0.65–0.80] versus 0.41 [95% CI 0.33–0.50]; CIN3+: 0.61 [95% CI 0.53–0.69] versus 0.33 [95% CI 0.23–0.45]). Summary receiver operating characteristic curve analysis demonstrated p16/Ki‐67 dual‐staining had better diagnostic accuracy for CIN2+ than HPV tests (area under the curve: 0.88 [95% CI 0.85–0.90] versus 0.79 [95% CI 0.75–0.82]). Pretest‐posttest probability (PPP) plots highlighted the superior performance of p16/Ki‐67 dual‐staining for colposcopy referrals in LSIL patients.
Conclusions
P16/Ki‐67 dual‐staining offers greater specificity for detecting CIN2+/CIN3+ in ASC‐US and LSIL triage, particularly for LSIL. It holds potential as an alternative to HPV tests in resource‐limited settings or LSIL cases, warranting further research to refine its application in diverse populations.