title: Quadrivalent HPV vaccination and risk of multiple sclerosis and other demyelinating diseases of the central nervous system.
abstract: OBJECTIVE
  Case reports have suggested a link between human papillomavirus (HPV) vaccination and development of multiple sclerosis and other demyelinating diseases.
  
  
  OBJECTIVE
  To investigate if quadrivalent HPV (qHPV) vaccination is associated with an increased risk of multiple sclerosis and other demyelinating diseases.
  
  
  METHODS
  Using nationwide registers we identified a cohort of all females aged 10 years to 44 years in Denmark and Sweden, followed up from 2006 to 2013, information on qHPV vaccination, and data on incident diagnoses of multiple sclerosis and other demyelinating diseases. The primary analysis used a cohort design including vaccinated and unvaccinated study participants. A secondary analysis used a self-controlled case-series design including only cases. Both analyses used a 2-year risk period following vaccination.
  
  
  METHODS
  Information on qHPV vaccination was obtained through the national vaccination and prescription registers.
  
  
  METHODS
  The primary outcomes were multiple sclerosis and a composite end point of other demyelinating diseases. Incidence rate ratios were estimated using Poisson regression, comparing rates of events in the 2-year risk periods following vaccination and in unvaccinated time periods.
  
  
  RESULTS
  The study included 3,983,824 females, among whom 789,082 received a total of 1,927,581 qHPV vaccine doses. During follow-up, 4322 multiple sclerosis cases and 3300 cases of other demyelinating diseases were identified, of which 73 and 90, respectively, occurred within the risk period. In the cohort analysis, there was no increased risk of multiple sclerosis (crude incidence rates, 6.12 events/100,000 person-years [95% CI, 4.86-7.69] and 21.54 events/100,000 person-years [95% CI, 20.90-22.20] for the vaccinated and unvaccinated periods; adjusted rate ratio, 0.90 [95% CI, 0.70-1.15]) or other demyelinating diseases (crude incidence rates, 7.54 events/100,000 person-years [95% CI, 6.13-9.27] and 16.14 events/100,000 person-years [95% CI, 15.58-16.71]; adjusted rate ratio, 1.00 [95% CI, 0.80-1.26]) associated with qHPV vaccination. Similarly, no increased risk was found using the self-controlled case-series design (multiple sclerosis: incidence ratio, 1.05 [95% CI, 0.79-1.38]; other demyelinating diseases: incidence ratio, 1.14 [95% CI, 0.88-1.47]).
  
  
  CONCLUSIONS
  In this study with nationwide coverage of 2 Scandinavian countries, qHPV vaccination was not associated with the development of multiple sclerosis or other demyelinating diseases. These findings do not support concerns about a causal relationship between qHPV vaccination and demyelinating diseases.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Nikolai Madrid
authors.initials: NM
authors.lastname: Scheller
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Svanström
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Björn
authors.initials: B
authors.lastname: Pasternak
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lisen
authors.initials: L
authors.lastname: Arnheim-Dahlström
authors.affiliation: Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Sundström
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden5Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Katharina
authors.initials: K
authors.lastname: Fink
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Hviid
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D003711:Demyelinating Diseases / Q000453:epidemiology*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D009103:Multiple Sclerosis / Q000453:epidemiology*; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000009:adverse effects*; D012306:Risk; D013548:Sweden / Q000453:epidemiology; D014611:Vaccination / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D053918:Papillomavirus Vaccines