title: The potential harms of primary human papillomavirus screening in over-screened women: a microsimulation study.
abstract: BACKGROUND
  It is well acknowledged that HPV testing should not be performed at young age and at short intervals. Cytological screening practices have shown that over-screening, i.e., from a younger age and at shorter intervals than recommended, is hard to avoid. We quantified the consequences of a switch to primary HPV screening for over-screened women, taking into account its higher sensitivity but lower specificity than cytology.
  
  
  METHODS
  The health effects of using the HPV test instead of cytology as the primary screening method were determined with the MISCAN-Cervix model. We varied the age women start screening and the interval between screens. In the sensitivity analyses, we varied the background risk of cervical cancer, the HPV prevalence, the discount rate, the triage strategy after cytology, and the test characteristics of both cytology and the HPV test.
  
  
  RESULTS
  For women screened 5 yearly from age 30, 32 extra deaths per 100,000 simulated women were prevented when switching from primary cytology to primary HPV testing. For annual screening from age 20, such a switch resulted in 6 extra deaths prevented. It was associated with 9,044 more positive primary screens in the former scenario versus 76,480 in the latter. Under all conditions, for women screened annually, switching to HPV screening resulted in a net loss of quality-adjusted life years.
  
  
  CONCLUSIONS
  For over-screened women, the harms associated with a lower test specificity outweigh the life years gained when switching from primary cytology to primary HPV testing. The extent of over-screening should be considered when deciding on inclusion of primary HPV screening in cervical cancer screening guidelines.
authors.affiliation: Department of Public Health, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. s.naber@erasmusmc.nl.
authors.forename: Steffie K
authors.identifier: http://orcid.org/0000-0001-8357-1738
authors.initials: SK
authors.lastname: Naber
authors.affiliation: Department of Public Health, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Inge M C M
authors.initials: IM
authors.lastname: de Kok
authors.affiliation: Department of Public Health, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Suzette M
authors.initials: SM
authors.lastname: Matthijsse
authors.affiliation: Department of Public Health, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: van Ballegooijen
mesh_terms: D000328:Adult; D003581:Cytodiagnosis; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology; D019057:Quality-Adjusted Life Years; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D055815:Young Adult
keywords: Computer simulation; Early detection of cancer; Human papillomavirus DNA tests; Papanicolaou test; Uterine cervical neoplasms