Assessing the Risk for Autoimmune Disorders Following Use of the Quadrivalent Human Papillomavirus Vaccine: the Ontario Grade 8 HPV Vaccine Cohort Study

Abstract

Introduction: In 2007 Ontario implemented a grade 8 quadrivalent human papillomavirus (qHPV) vaccination program targeting the virus that causes cervical cancer. Despite being 6 years post-implementation, few post-licensure studies have assessed the safety of the qHPV vaccine in this adolescent population. Since autoimmune disorders are often targeted for post-marketing surveillance by regulatory agencies, it is important to assess the risk of developing an autoimmune disorder post-qHPV vaccination.

Objectives: The objectives of this thesis were to assess the risk for developing an autoimmune disorder following qHPV vaccination, assess for effect modification by the presence of predisposing risk factors, identify the period of highest risk and explore the risk for individual autoimmune disorders.

Methods: A population-based retrospective cohort of girls eligible for Ontario’s qHPV vaccination program was identified using population-based databases. The risk of autoimmune disorders following qHPV vaccination was ascertained using the self-controlled case series method.

Results: The risk of developing a new autoimmune disorder, adjusted for age, seasonality, concurrent vaccines and infections was 1.28 (95% CI: 0.87 – 1.89), and this association was independent of a history of immune-mediated disorders (p=0.39). The risk was not increased during days 7-24 post-vaccination (adjusted RR = 0.87, 95% CI: 0.43 – 1.74), but appeared to increase thereafter (adjusted RR = 1.36, 95% CI: 0.77 – 2.41 and RR = 1.62, 95% CI 0.94 – 2.78 respectively, for days 25 – 42 and days 43 – 60), although these differences were non-significant. The risk may be increased for certain disorders including Bell’s palsy (RR = 2.30, 95% CI: 0.67 – 7.95), systemic autoimmune rheumatic disorders (RR = 1.84, 95% CI: 0.42 – 8.02), Hashimoto’s disease (RR = 1.39, 95% CI: 0.46 – 4.22), and juvenile rheumatoid arthritis (RR = 1.31, 95% CI: 0.83 – 2.08), although none of these associations were statistically significant.

Conclusion: This thesis demonstrated that no statistically significant increased risk for autoimmune disorders following qHPV vaccination was detected. However, there remains some uncertainty about the safety of the qHPV vaccine for a subset of the autoimmune disorders. The results from this analysis need to be pooled with those of other studies to confirm whether these are true safety signals.