Co-testing for detection of high-grade cervical intraepithelial neoplasia and cancer compared with cytology alone: a meta-analysis of randomized controlled trials

Human papillomavirus (HPV) DNA testing combined with cytology has been recommended as a primary cervical cancer screening strategy. PubMed/MEDLINE, Embase, the Cochrane Library and the NIH trial registry were searched for randomized controlled trials comparing co-testing with cytology alone for the detection of high-grade CIN lesions and cancers. Of 1156 articles identified, four met inclusion criteria. The performance of co-testing and cytology alone was compared at baseline screening, second round screening and overall. Cumulative meta-analysis, Beggs test, Eggers test and sensitivity analysis were performed. At baseline, co-testing was associated with a significantly higher detection rate of CIN 2 [risk ratio (RR) 1.41, 95 confidence interval (CI): 1.12, 1.76] and a non-significantly higher CIN 3 detection rate (RR 1.15, 95 CI: 0.99, 1.33). At second round screening, co-testing was associated with significantly lower detection rates of both CIN 2 and CIN 3 (RR 0.77, 95 CI: 0.63, 0.93; RR 068, 95 CI: 0.55, 0.85). The overall detection rate did not differ between co-testing and cytology alone for CIN 2 (RR: 119, 95 CI: 0.99, 1.46) or CIN3 (RR: 0.99, 95 CI: 0.87, 1.14). Co-testing increases the detection of CIN2 lesions at baseline and significantly decreases the detection rates of CIN2 or CIN3 lesions at subsequent screening compared with cytology alone.