PMID- 33187968 OWN - NLM STAT- MEDLINE DCOM- 20210825 LR - 20210825 IS - 1538-7755 (Electronic) IS - 1055-9965 (Linking) VI - 30 IP - 3 DP - 2021 Mar TI - Cervical Cancer Screening: Comparison of Conventional Pap Smear Test, Liquid-Based Cytology, and Human Papillomavirus Testing as Stand-alone or Cotesting Strategies. PG - 474-484 LID - 10.1158/1055-9965.EPI-20-1003 [doi] AB - 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. CI - (c)2020 American Association for Cancer Research. FAU - Liang, Linda A AU - Liang LA AD - Epidemiology, Department of Sports and Health Sciences, Technical University of Munich, Munich, Germany. FAU - Einzmann, Thomas AU - Einzmann T AD - Department of Obstetrics and Gynecology, University Hospital Cologne, Cologne, Germany. FAU - Franzen, Arno AU - Franzen A AD - Department of Obstetrics and Gynecology, Kemperhof, Gemeinschaftsklinikum Mittelrhein, Koblenz, Germany. FAU - Schwarzer, Katja AU - Schwarzer K AUID- ORCID: 0000-0003-2203-9224 AD - VivaQ MVZ, Mainz, Germany. FAU - Schauberger, Gunther AU - Schauberger G AUID- ORCID: 0000-0002-0392-1580 AD - Epidemiology, Department of Sports and Health Sciences, Technical University of Munich, Munich, Germany. FAU - Schriefer, Dirk AU - Schriefer D AUID- ORCID: 0000-0002-7524-7628 AD - Epidemiology, Department of Sports and Health Sciences, Technical University of Munich, Munich, Germany. AD - Center of Clinical Neuroscience, University Hospital Carl Gustav Carus Dresden, Dresden, Germany. FAU - Radde, Kathrin AU - Radde K AD - Epidemiology, Department of Sports and Health Sciences, Technical University of Munich, Munich, Germany. FAU - Zeissig, Sylke R AU - Zeissig SR AUID- ORCID: 0000-0002-0743-6128 AD - Cancer Registry of Rhineland-Palatinate, Mainz, Germany. FAU - Ikenberg, Hans AU - Ikenberg H AD - Cytomol MVZ, Frankfurt, Germany. FAU - Meijer, Chris J L M AU - Meijer CJLM AD - Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, the Netherlands. FAU - Kirkpatrick, Charles J AU - Kirkpatrick CJ AD - Institute of Pathology, University Medical Center, Johannes Gutenberg University, Mainz, Germany. FAU - Kolbl, Heinz AU - Kolbl H AD - Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. FAU - Blettner, Maria AU - Blettner M AD - Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center, Johannes Gutenberg University, Mainz, Germany. FAU - Klug, Stefanie J AU - Klug SJ AUID- ORCID: 0000-0003-3523-1362 AD - Epidemiology, Department of Sports and Health Sciences, Technical University of Munich, Munich, Germany. sekretariat.klug@tum.de. LA - eng PT - Comment PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201113 PL - United States TA - Cancer Epidemiol Biomarkers Prev JT - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JID - 9200608 SB - IM CIN - Cancer Epidemiol Biomarkers Prev. 2021 Mar;30(3):432-434. PMID: 33857013 CON - Cancer Epidemiol Biomarkers Prev. 2021 Mar;30(3):432-434. PMID: 33857013 MH - *Alphapapillomavirus MH - Cohort Studies MH - Colposcopy MH - Early Detection of Cancer MH - Female MH - Humans MH - Papanicolaou Test MH - Papillomaviridae/genetics MH - *Papillomavirus Infections/diagnosis MH - Pregnancy MH - Sensitivity and Specificity MH - *Uterine Cervical Neoplasms/diagnosis MH - Vaginal Smears EDAT- 2020/11/15 06:00 MHDA- 2021/08/26 06:00 CRDT- 2020/11/14 05:24 PHST- 2020/07/09 00:00 [received] PHST- 2020/09/17 00:00 [revised] PHST- 2020/11/02 00:00 [accepted] PHST- 2020/11/15 06:00 [pubmed] PHST- 2021/08/26 06:00 [medline] PHST- 2020/11/14 05:24 [entrez] AID - 1055-9965.EPI-20-1003 [pii] AID - 10.1158/1055-9965.EPI-20-1003 [doi] PST - ppublish SO - Cancer Epidemiol Biomarkers Prev. 2021 Mar;30(3):474-484. doi: 10.1158/1055-9965.EPI-20-1003. Epub 2020 Nov 13.