title: Cancer incidence in Denmark following exposure to poliovirus vaccine contaminated with simian virus 40.
abstract: BACKGROUND
  Early poliovirus vaccines were accidentally contaminated with simian virus 40 (SV40). In Denmark, poliovirus vaccine was administered to most children from 1955 through 1961. SV40 DNA sequences have been detected in several human malignancies, including mesothelioma, ependymoma, choroid plexus tumors, and non-Hodgkin's lymphoma. To clarify whether SV40 infection increases risk of these cancers or of cancers arising in children, we examined cancer incidence in three Danish birth cohorts.
  
  
  METHODS
  Population-based cancer incidence data from 1943 through 1997 were obtained from the Danish Cancer Registry. The relationship between exposure to SV40-contaminated vaccine and cancer incidence was evaluated by examining incidence in birth cohorts that differed in exposure to SV40-contaminated vaccine. In addition, cancer incidence was examined in children who were 0-4 years of age before, during, and after the period of vaccine contamination. Incidence was compared using Poisson regression, adjusting for age differences. All statistical tests were two-sided.
  
  
  RESULTS
  After 69.5 million person-years of follow-up, individuals exposed to SV40-contaminated poliovirus vaccine as infants (i.e., born 1955-1961) or children (i.e., born 1946-1952) had lower overall cancer risk (age-adjusted relative risk [RR] = 0.86, 95% confidence interval [CI] = 0.81 to 0.91 and RR = 0.79, 95% CI = 0.75 to 0.84, respectively; P<.001 for both) than unexposed individuals (i.e., born 1964-1970, after the vaccine was cleared of SV40 contamination). Specifically, SV40 exposure was not associated with increased incidence of mesothelioma, ependymoma, choroid plexus tumor, or non-Hodgkin's lymphoma. After 19.5 million person-years of follow-up, incidence of all cancers combined, of intracranial tumors, and of leukemia among children aged 0-4 years was also not associated with SV40 exposure. Ependymoma incidence was higher during the exposed period than during the unexposed period (RR = 2.59, 95%CI = 1.36 to 4.92; P =.004 versus the period before contamination); however, incidence peaked in 1969, after the vaccine was cleared of SV40.
  
  
  CONCLUSIONS
  Exposure to SV40-contaminated poliovirus vaccine in Denmark was not associated with increased cancer incidence.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD 20892, USA. engelse@exchange.nih.gov
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engels
authors.forename: Hormuzd A
authors.initials: HA
authors.lastname: Katki
authors.forename: Nete M
authors.initials: NM
authors.lastname: Nielsen
authors.forename: Jeanette F
authors.initials: JF
authors.lastname: Winther
authors.forename: Henrik
authors.initials: H
authors.lastname: Hjalgrim
authors.forename: Flemming
authors.initials: F
authors.lastname: Gjerris
authors.forename: Philip S
authors.initials: PS
authors.lastname: Rosenberg
authors.forename: Morten
authors.initials: M
authors.lastname: Frisch
mesh_terms: D002675:Child, Preschool; D015331:Cohort Studies; D016001:Confidence Intervals; D003718:Denmark / Q000453:epidemiology; D004340:Drug Contamination; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000453:epidemiology* / Q000821:virology*; D016012:Poisson Distribution; D023321:Poliovirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D012042:Registries; D012306:Risk; D013539:Simian virus 40
chemical_list: D023321:Poliovirus Vaccines