Screening For Cervical Cancer With Human Papillomavirus Testing: Stand-Alone Is Preferable Over Co-Testing With Cytology

Abstract Background Cervical cancer screening can be conducted with cytology and Human Papillomavirus (HPV) testing but few studies have compared the latter directly to concomitant testing (co-testing). We compared these strategies to determine appropriate screening. Methods Within a randomised population-based cohort study conducted around Mainz, Germany, eligible women (≥30 years) were screened via Pap smear, liquid-based cytology (LBC) and HPV testing (HC2) and HPV genotyped post hoc (PCR). These tests formed three strategies: cytology (Pap or LBC) and HPV (HC2 or PCR) stand-alone and co-testing. Screen positives and 5% negative women were invited to colposcopy. Absolute and relative sensitivity, specificity, false positive rates (FPR) and number needed to colposcopy to detect one lesion (NNC) were calculated. Estimates were crude and verification bias-adjusted using stratified sampling with bootstrapped confidence intervals. Results Of 2,627 screened women, cytology stand-alone demonstrated lowest sensitivities (47%) and highest specificities (97%-99%) while HPV stand-alone demonstrated higher sensitivities (79%-95%) but lower specificities (94%-95%). Co-testing increased sensitivity (84%-99%) but not specificity (92%-95%). Relative sensitivities were similar between crude and adjusted estimates, with greater detection via HPV-based strategies. Specificity of co-testing with LBC relative to HPV stand-alone was near unity (0.99, 95% CI 0.99-1.00) but significantly lower than unity with Pap co-testing. FPR and NNC were greatest under co-testing. Conclusions HPV stand-alone screening in women over 30 years appears appropriate over co-testing as a screening strategy. Key messages Co-testing for cervical cancer does not appear to add any benefit in detection and may introduce unnecessary harms compared to HPV stand-alone screening.