Improving Cervical Cancer Screening in Women Under 40: Effectiveness of Co-Testing with 3-Type HPV mRNA and Cytology in Northern Norway

Abstract

Abstract

Objective: To evaluate whether co-testing with a 3-type HPV mRNA test (PreTect SEE), targeting HPV types 16, 18, and 45, in combination with liquid-based cytology (ThinPrep), improves sensitivity and risk stratification for detecting high-grade cervical lesions (CIN2+) compared to cytology alone, in women under 40 years of age in Northern Norway.

Methods: We analyzed data from 11,395 women under 40, screened between 2013 and 2015, with follow-up through 2023. The intervention group (2,807 women) underwent co-testing in 2013–2014 with ThinPrep cytology and the PreTect SEE HPV mRNA test, while the control group (8,588 women) received cytology alone in 2015. The study endpoint was histologically confirmed CIN2+.

Results: The overall prevalence of CIN2+ was comparable between the co-tested (9.3%) and cytology-only (9.6%) groups. However, co-testing enabled more accurate risk stratification and improved diagnostic performance. The sensitivity for detecting CIN2+ was significantly higher with co-testing (71.0%) than with cytology alone (63.7%), corresponding to a 7.3 percentage point absolute increase and an 11.4% relative improvement (p = 0.034). Among HPV mRNA-positive women, 46.0% developed CIN2+, compared to only 5.2% among HPV mRNA-negative women (p < 0.0001). Women with double-positive results (HPV mRNA positive and abnormal cytology) had the highest CIN2+ risk at 58.3%, while double-negative women had a very low risk at 3.3% (p < 0.0001). Notably, no cervical cancer cases occurred in the double-negative co-tested group. Women with a positive HPV mRNA test and normal cytology had a significantly higher CIN2+ risk than women with abnormal cytology and negative HPV mRNA (35.3% versus 23.0%, p = 0.011).

Conclusions: Co-testing with the 3-type HPV mRNA test and cytology significantly improves both risk stratification and sensitivity for detecting CIN2+ compared to cytology alone. These findings support the integration of co-testing into cervical cancer screening programs for women under 40 to improve precision, enhance early detection, and reduce the risk of missed high-grade lesions.