Cervical Cancer Screening: Comparison of conventional Pap smear test, liquid-based cytology and human papillomavirus testing as stand-alone or co-testing strategies.

Background:Some countries have implemented stand-alone Human Papillomavirus (HPV) testing while others consider co-testing for cervical cancer screening. We compared both strategies within a population-based study. Methods:The MARZY cohort study was conducted in Germany. Randomly selected women from population registries aged ≥30 years (n=5275) were invited to screening with Pap smear, liquid-based cytology (LBC, ThinPrep®) and HPV testing (Hybrid Capture®2, HC2). Screen positive participants (ASC-US+ or high-risk HC2 (hrHC2)) and a random 5% sample of screen negatives were referred to colposcopy. Post hoc HPV genotyping was conducted by GP5+/6+ PCR-EIA with reverse line blotting. Sensitivity, specificity (adjusted for verification bias) and potential harms including number of colposcopies needed to detect 1 precancerous lesion (NNC) were calculated. Results:In 2627 screened women, cytological sensitivities (Pap, LBC: 47%) were lower than HC2 (95%) and PCR (79%) for CIN2+. Co-testing demonstrated higher sensitivities (HC2 co-testing: 99%; PCR co-testing: 84%), but at the cost of lower specificities (92%-95%) compared to HPV stand-alone (HC2: 95%; PCR: 94%) and cytology (97% or 99%). Co-testing versus HPV stand-alone showed equivalent relative sensitivity (HC2: 1.06, 95% CI 1.00-1.21; PCR: 1.07, 95% 1.00-1.27). Relative specificity of Pap co-testing with either HPV test was inferior to stand-alone HPV. LBC co-testing demonstrated equivalent specificity (both tests: 0.99, 95% CI 0.99-1.00). NNC was highest for Pap co-testing. Conclusions:Co-testing offers no benefit in detection over stand-alone HPV testing resulting in more false positive results and colposcopy referrals. Impact:HPV stand-alone screening offers a better balance of benefits and harms than co-testing.