Predictive value of p16/Ki-67 immunocytochemistry for triage of women with abnormal Papanicolaou test in cervical cancer screening: a systematic review and meta-analysis

BACKGROUND: The Papanicolaou (Pap) test is one screening strategy used to prevent cervical cancer in developed countries. The p16/Ki-67 immunocytochemistry is a triage test performed on Pap smears in women with atypical squamous cells of undetermined significance (ASCUS) or low grade squamous intraepithelial lesion. OBJECTIVE: Our objective was to review studies investigating the diagnostic performance of p16/Ki-67 dual stain for triage of women with abnormal Pap tests. DESIGN: We conducted a systematic review and meta-analysis of diagnostic test accuracy studies. SETTINGS: We followed the protocol of systematic review of diagnostic accuracy studies. PATIENTS AND METHODS: We searched PubMed, The Cochrane Library, BioMed Central, and ClinicalTrials.gov for relevant studies. We included research that assessed the accuracy of p16/Ki-67 dual stain and high risk human papillomavirus testing for triage of abnormal Pap smears. Review articles and studies that provided insufficient data to construct 2×2 tables were excluded. Data synthesis was conducted using a random-effects model. MAIN OUTCOME MEASURES: Sensitivity and specificity. RESULTS: In seven studies encompassing 2628 patients, the pooled sensitivity and specificity of p16/Ki-67 for triage of abnormal Pap smear results were 0.91 (95% CI, 0.89 to 0.93) and 0.64 (95% CI, 0.62 to 0.66), respectively. No study used a case-control design. A subgroup analysis involving liquid-based cytology showed a sensitivity of 0.91 (95%CI, 0.89 to 0.93) and specificity of 0.64 (95%CI, 0.61 to 0.66). CONCLUSIONS: Our meta-analysis of p16/Ki-67 dual stain studies showed that the test achieved high sensitivity and moderate specificity for p16/Ki-67 immunocytochemistry for high-grade squamous intraepithelial lesion and cervical cancer. We suggest that p16/Ki-67 dual stain might be a reliable ancillary method identifying high-grade squamous intraepithelial lesions in women with abnormal Pap tests. LIMITATIONS: No study in the meta-analysis examined the accuracy of the p16/Ki-67 dual stain for interpretation of glandular neoplasms.