Background: The HPV-16/18 AS04-adjuvanted vaccine is indicated for protection against cervical cancer. The risk of AD after vaccination needs to be evaluated.
Objectives: To assess the risk of AD (2 co-primary endpoints: neuroinflammatory/ophthalmic and other) in women aged 9–25 years within 1 year after the first dose of HPV-16/18 vaccine.
Methods: Four cohorts (65,000 subjects each) were defined in the UK Clinical Practice Research Datalink General Practice OnLine Database: 1 exposed female cohort (≥ 1 vaccine dose Sep2008–Aug2010) and 3 unexposed cohorts: 1 concurrent male (Sep2008–Aug2010), 1 historical male and 1 historical female (Sep2005–Aug2007) (NCT01953822). AD risk was compared between cohorts (with the historical cohort as reference group) by Poisson regression. Sensitivity analysis considered confirmed and non-confirmed cases.
Results: In all cohorts, 155 subjects had AD first symptom within 1 year follow-up; 109 were confirmed AD. The main analysis based on confirmed cases showed no increased risk of neuroinflammatory/ophthalmic AD: no confirmed cases in female cohorts and incidence rate ratios (IRR) (95%CI)=0.95 (0.06–15.18) in male cohorts; for other AD: IRR=1.41 (0.86–2.31) in female and IRR=1.77 (0.94–3.35) in male cohorts. Disease-specific risks were evaluated for 3 diseases with ≥ 10 cases in both female cohorts: Crohn's disease (IRR=1.21 [0.37–3.95] and IRR=4.22 [0.47–38.02] for female and male cohorts, respectively), autoimmune thyroiditis (IRR=3.75 [1.25–11.31] for female and no confirmed cases for male cohorts) and type 1 diabetes mellitus (IRR=0.30 [0.11–0.83] for female [risk adjusted for male cohort effect] and IRR=2.46 [1.08–5.60] for male cohorts). Sensitivity analysis confirmed main analyses except for autoimmune thyroiditis in females, IRR=1.45 (0.79–2.64).
Conclusions: There was no evidence of an increased risk of AD in women aged 9–25 years after HPV-16/18 vaccination. After disease-specific analysis, the risk of autoimmune thyroiditis was increased and the risk of type 1 diabetes was decreased in vaccinated women.
