HPV Testing Versus Cytology for Cervical Cancer Screening Among Women 50 Years and Older: Evidence From the HPV FOCAL Randomized Controlled Trial

ABSTRACT

Evidence on the comparative effectiveness of HPV testing versus cytology specifically in women aged ≥ 50 years who are approaching screening cessation remains limited. This analysis included 6471 women aged ≥ 50 at baseline screening in the HPV FOCAL randomized clinical trial. Women were randomly allocated to receive cytology (Control Group, n  = 3248, 50.19%) or HPV testing (Intervention Group, n  = 3223, 49.81%) at baseline, with co‐testing at 48‐month exit. We calculated incidence rates and risk ratios for CIN2+ detection over follow‐up and compared missed lesions at exit by screening method. At the 48‐month exit, CIN2+ detection was lower among HPV baseline‐negative women than among those in the cytology group (1.61/1000 [95% CI, 0.52–3.76] vs. 3.15/1000 [95% CI, 1.51–5.78]; risk ratio, 0.51 [95% CI, 0.11–0.91]), reflecting higher baseline detection with HPV testing and fewer prevalent lesions at exit. Even with cytology re‐screening at 2 years, 50% of CIN2+ cases were missed compared to 30% with HPV testing. After adjusting for age, education, smoking status, and lifetime sexual partners, the hazard ratio for CIN2+ comparing HPV to cytology was 0.44 (95% CI, 0.22–0.88). Among women aged ≥ 50 years, HPV primary screening was more effective than cytology at detecting CIN2+ lesions and was associated with a continued lower subsequent risk following a negative HPV test, supporting its use in cervical cancer screening programs in this age cohort.