The Use and Neurological Safety of the Quadrivalent Human Papillomavirus (HPV) Vaccine: The Ontario Grade 8 HPV Vaccine Cohort Study
Lim, Wen Ting
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The quadrivalent (q-) human papillomavirus (HPV) vaccine is praised for its near perfect efficacy of 98% in the per-protocol population and minimal safety concerns. Adherence to the dosing schedule of 0, 2 and 6 months outside clinical trials has not yet been described. Furthermore, clinical trials were underpowered to detect rare, but serious, adverse events including convulsions, seizures and epilepsy in young girls targeted by American and Canadian national advisory committees. This retrospective cohort study followed Grade 8 girls eligible for Ontario’s HPV immunization program during the 2007/08 to 2010/11 campaign years. Using Ontario’s immunization and health databases, baseline characteristics, qHPV vaccination, dates of qHPV vaccination and diagnoses of serious neurological events were identified for each cohort member. The proportions of girls who initiated and completed the qHPV vaccine program were determined. Adherence to the recommended dosing intervals and for ‘time-to-series completion’ was calculated as the proportion of eligible girls whose number of days between doses complied with the recommended dosing interval. A self-matched, case only approach was used to estimate the age-adjusted rate ratio (RR) of neurological events in the 0-30 day period following qHPV vaccination. The primary study endpoint was a composite of the first occurrence of a convulsion, seizure or epilepsy. Secondarily, an epileptic seizure only endpoint was assessed, as were the influence of a number of predisposing risk factors. An overall uptake of 50.24% was observed, of which, 87.02% received at least three doses. Adherence to the recommended dosing interval was most difficult in scheduling of the second dose (70.80%). There was no increased risk observed for the primary endpoint in the 0-30 days following qHPV vaccination (RR 1.01, 95% CI 0.92-1.10). However, this association was modified in girls with predisposing risk factors for epilepsy. There was an increased risk observed for the epileptic seizure only endpoint (RR 1.64, 95% CI 1.28-2.10). In Ontario, the overall uptake of the qHPV vaccine is low. Once initiated, series completion is high, with the majority receiving the vaccine in a timely manner. A risk for epileptic seizures following vaccination may be limited to girls with predisposing risk factors.