Accuracy of Combined Visual Inspection with Acetic Acid and Cervical Cytology Testing as a Primary Screening Tool for Cervical Cancer: a Systematic Review and Meta-Analysis

Background: The performance of combined testing visual inspection with acetic acid (VIA) and cervicalcytology tests might differ from one setting to another. The average estimate of the testing accuracy across studiesis informative, but no meta-analysis has been carried out to assess this combined method.
Objective: The objectiveof this study was to estimate the average sensitivity and specificity of the combined VIA and cervical cytologytests for the detection of cervical precancerous lesions. Materials and
Methods: We conducted a systematic reviewand a meta-analysis, according to the Cochrane Handbook for Systematic Review of Diagnostic Test Accuracy.We considered two cases. In the either-positive result case, a positive result implies positivity in at least one ofthe tests. A negative result implies negativity in both tests. In the both-positive case, a positive result implieshaving both tests positive. Eligible studies were identified using Pubmed, Embase, Website of Science, CINHALand COCRANE databases. True positive, false positive, false negative and true negative values were extracted.Estimates of sensitivity and specificity, positive and negative likelihood (LR) and diagnostic odds ratios (DOR)were pooled using a hierarchical random effect model. Hierarchical summary receiver operating characteristics(HSROC) were generated and heterogeneity was verified through covariates potentially influencing the diagnosticodds ratio. Findings: Nine studies fulfilled inclusion criteria and were included in the analysis. Pooled estimatesof the sensitivities of the combined tests in either-positive and both-positive cases were 0.87 (95% CI: 0.83-0.90)and 0.38 (95% CI: 0.29-0.48), respectively. Corresponding specificities were 0.79 (95% CI: 0.63-0.89) and 0.98(95% CI: 0.96-0.99) respectively. The DORs of the combined tests in either-positive or both-positive result caseswere 27.7 (95% CI: 12.5-61.5) and 52 (95% CI: 22.1-122.2), respectively. When including only articles withoutpartial verification bias and also a high-grade cervical intraepithelial neoplasia as a threshold of the disease,DOR of combined test in both-positive result cases remained the highest. However, DORs decreased to 12.1 (95%CI: 6.05-24.1) and 13.8 (95% CI: 7.92-23.9) in studies without partial verification bias for the combined tests inthe either-positive and both-positive result cases, respectively. The screener, the place of study and the size ofthe population significantly influenced the DOR of combined tests in the both-positive result case in restrictionanalyses that considered only articles with CIN2+ as disease threshold.
Conclusions: The combined test in theeither-positive result case has a high sensitivity, but a low specificity. These results suggest that the combined testshould be considered in developing countries as a primary screening test if facilities exist to confirm, throughcolposcopy and biopsy, a positive result.