Cervical Cancer Screening: Comparison of Conventional Pap Smear Test, Liquid-Based Cytology, and Human Papillomavirus Testing as Stand-alone or Cotesting Strategies

Cancer Epidemiol Biomarkers Prev. 2021 Mar;30(3):474-484. doi: 10.1158/1055-9965.EPI-20-1003. Epub 2020 Nov 13.


Background: Some countries have implemented stand-alone human papillomavirus (HPV) testing while others consider cotesting 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 = 5,275) were invited to screening with Pap smear, liquid-based cytology (LBC, ThinPrep), and HPV testing (Hybrid Capture2, 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 2,627 screened women, cytological sensitivities (Pap, LBC: 47%) were lower than HC2 (95%) and PCR (79%) for CIN2+. Cotesting demonstrated higher sensitivities (HC2 cotesting: 99%; PCR cotesting: 84%), but at the cost of lower specificities (92%-95%) compared with HPV stand-alone (HC2: 95%; PCR: 94%) and cytology (97% or 99%). Cotesting versus HPV stand-alone showed equivalent relative sensitivity [HC2: 1.06, 95% confidence interval (CI), 1.00-1.21; PCR: 1.07, 95% CI, 1.00-1.27]. Relative specificity of Pap cotesting with either HPV test was inferior to stand-alone HPV. LBC cotesting demonstrated equivalent specificity (both tests: 0.99, 95% CI, 0.99-1.00). NNC was highest for Pap cotesting.

Conclusions: Cotesting 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 cotesting.See related commentary by Wentzensen and Clarke, p. 432.

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