Comparative performance of standalone E6/E7 mRNA testing versus a combined DNA genotyping and viral load assay for detecting cervical high-grade lesions: a retrospective paired study

OBJECTIVE: To compare the diagnostic performance of standalone E6/E7 mRNA testing versus a combined HPV DNA genotyping and viral load assay for detecting cervical high-grade lesions (CIN2+) and to validate performance, biological rationale, and clinical utility. METHODS: This single-center, retrospective, paired diagnostic accuracy study included 150 women in the primary cohort and 100 in an independent validation cohort, all referred for colposcopy. Participants underwent both the E6/E7 mRNA test (Aptima) and the combined DNA test (genotyping + Hybrid Capture 2 viral load) within one month prior to biopsy. Histopathology was the reference standard. Analyses included diagnostic performance metrics, correlation of viral load with histopathology, subgroup assessments, and follow-up of 65 DNA+/mRNA- women. RESULTS: In the primary cohort, the sensitivity of the mRNA assay (87.7%) was not significantly different from that of the DNA test (94.7%, P=0.221), but the specificity was significantly higher (P