Genotype-Specific HPV mRNA Triage Improves Colposcopy Efficiency Compared with Cytology and ATHENA-Derived Triage: A Population-Based Study of HPV DNA-Positive Women

BACKGROUND: Effective triage of HPV DNA-positive women is needed to reduce unnecessary colposcopies while maintaining cervical cancer prevention. We evaluated genotype-specific 7-type HPV E6/E7 mRNA triage in a real-world screening cohort. METHODS: In this population-based single-centre study at the University Hospital of North Norway, 42,791 women underwent primary screening with the cobas HPV DNA assay during the period 2019-2024. Among 2370 HPV DNA-positive women, reflex cytology, 7-type HPV mRNA testing, and an ATHENA-derived triage strategy were compared using histologically confirmed CIN3+ through 31 December 2025 as the endpoint. RESULTS: CIN3+ was detected in 60/2370 women (2.5%). Test positivity was 47.0% for cytology, 54.7% for ATHENA-derived triage, and 33.4% for HPV mRNA. Sensitivity was 78.3%, 86.7%, and 73.3%; specificity was 53.8%, 46.1%, and 67.7%; and PPV was 4.2%, 4.0%, and 5.6%, respectively. Colposcopies per CIN3+ detected were 23.7, 24.9, and 18.0. CONCLUSIONS: HPV mRNA triage improved referral precision and colposcopy efficiency, but with lower sensitivity than ATHENA-derived triage. These findings support 7-type HPV mRNA testing as a potentially useful molecular triage option where structured follow-up is feasible.