Circulating micrornas as potential diagnostic biomarkers for cervical intraepithelial neoplasia and cervical cancer: a systematic review and meta-analysis

Background Cervical cancer is a prevalent malignancy of the female reproductive system. Cervical intraepithelial neoplasia (CIN) is a precursor lesion for CC. Various studies have examined circulating microRNAs (miRNAs) as potential early diagnostic markers for CC and CIN. However, the findings have been inconclusive. Therefore, it is necessary to evaluate the diagnostic accuracy and identify potential sources of variability among these studies. Methods: The PubMed, Cochrane Library, Embase, and Web of Science databases were searched to identify relevant literature. Then, Stata 14.0 was utilized to calculate summary estimates for diagnostic parameters, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (ROC). To scrutinize the heterogeneity, the Cochran-Q test and I2 statistic were utilized. As significant heterogeneity was observed, the random effects model was chosen. To explore potential sources of the heterogeneity, subgroup and regression analyses were conducted. Results: We analysed 12 articles reporting on 24 studies involving 1817 patients and 1731 healthy controls. The pooled sensitivity was 0.77 (95% CI 0.73-0.81), the specificity was 0.81 (95% CI 0.73-0.86), the PLR was 3.99 (95% CI 2.81-5.65), the NLR was 0.28 (95% CI 0.23-0.35), the DOR was 14.18 (95% CI 8.47-23.73), and the area under the curve (AUC) was 0.85 (95% CI 0.81-0.87). Subgroup analysis revealed that multiple miRNAs can improve diagnostic performance; the pooled sensitivity of multiple miRNAs was 0.78 (95% CI 0.68-0.86), the specificity was 0.85 (95% CI 0.78-0.90), and the AUC was 0.89 (95% CI 0.86-0.91). Conclusion: This study suggested that circulating microRNAs may be biomarkers for early CC diagnosis.