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CMAJ. 2018 May 28;190(21):E648-E655. doi: 10.1503/cmaj.170871.

Quadrivalent human papillomavirus vaccination in girls and the risk of autoimmune disorders: the Ontario Grade 8 HPV Vaccine Cohort Study.

Author information

1
Department of Public Health Sciences (Liu, Lévesque), Queen's University, Kingston, Ont.; Department of Epidemiology, Biostatistics and Occupational Health (Smith), McGill University, Montréal, Que. Division of Allergy and Immunology, Department of Medicine (Ellis), Queen's University, Kingston, Ont.; Allergy Research Unit (Ellis), Kingston General Hospital, Kingston, Ont.; School of Mathematics and Statistics (Whitaker, Farrington), The Open University, Milton Keynes, UK; Vaccine Safety Section, Centre for Immunization and Respiratory Infectious Diseases (Law [retired from the Public Health Agency of Canada June 2015]), Public Health Agency of Canada, Ottawa, Ont.; Institute for Clinical Evaluative Sciences (Kwong, Lévesque), Toronto, Ont.; Public Health Ontario (Kwong), Toronto, Ont.; Department of Family and Community Medicine (Kwong), University of Toronto, Toronto, Ont.; Leslie Dan Faculty of Pharmacy (Lévesque), University of Toronto, Toronto, Ont.
2
Department of Public Health Sciences (Liu, Lévesque), Queen's University, Kingston, Ont.; Department of Epidemiology, Biostatistics and Occupational Health (Smith), McGill University, Montréal, Que. Division of Allergy and Immunology, Department of Medicine (Ellis), Queen's University, Kingston, Ont.; Allergy Research Unit (Ellis), Kingston General Hospital, Kingston, Ont.; School of Mathematics and Statistics (Whitaker, Farrington), The Open University, Milton Keynes, UK; Vaccine Safety Section, Centre for Immunization and Respiratory Infectious Diseases (Law [retired from the Public Health Agency of Canada June 2015]), Public Health Agency of Canada, Ottawa, Ont.; Institute for Clinical Evaluative Sciences (Kwong, Lévesque), Toronto, Ont.; Public Health Ontario (Kwong), Toronto, Ont.; Department of Family and Community Medicine (Kwong), University of Toronto, Toronto, Ont.; Leslie Dan Faculty of Pharmacy (Lévesque), University of Toronto, Toronto, Ont. linda.levesque@utoronto.ca.

Abstract

BACKGROUND:

Despite demonstrated effectiveness in real-world settings, concerns persist regarding the safety of the quadrivalent human papillomavirus (HPV4) vaccine. We sought to assess the risk of autoimmune disorders following HPV4 vaccination among grade 8 girls eligible for Ontario's school-based HPV vaccination program.

METHODS:

We undertook a population-based retrospective cohort study using Ontario's administrative health and vaccination databases from 2007 to 2013. The self-controlled case series method was used to compare the rate of a composite end point of autoimmune disorders diagnosed during days 7-60 post-vaccination ("exposed" follow-up) to that at any other time ("unexposed"). The analysis was repeated to assess the effect of a history of immune-mediated diseases and time since vaccination. We also conducted an exploratory analysis of individual autoimmune disorders. Rate ratios and 95% confidence intervals (CIs) were estimated using conditional Poisson regression, adjusted for age, seasonality, concomitant vaccinations and infections.

RESULTS:

The study cohort consisted of 290 939 girls aged 12-17 years who were eligible for vaccination between 2007 and 2013. There was no significant risk for developing an autoimmune disorder following HPV4 vaccination (n = 681; rate ratio 1.12, 95% CI 0.85-1.47), and the association was unchanged by a history of immune-mediated disorders and time since vaccination. Exploratory analyses of individual autoimmune disorders found no significant risks, including for Bell palsy (n = 65; rate ratio 1.73, 95% CI 0.77-3.89), optic neuritis (n = 67; rate ratio 1.57, 95% CI 0.74-3.33) and Graves disease (n = 47; rate ratio 1.55, 95% CI 0.92-2.63).

INTERPRETATION:

We did not observe an increased risk of autoimmune disorders following HPV4 vaccination among teenaged girls. These findings should reassure parents and health care providers.

Conflict of interest statement

Competing interests: Leah Smith is now employed by the Canadian Cancer Society, a charitable organization that promotes HPV vaccination and has received funds from Merck. However, this study was completed before Dr. Smith’s employment at the Canadian Cancer Society. Anne Ellis reports funding from ALK-Abelló, AstraZeneca, Bayer, Merck, Novartis, Pediapharm, Pfizer, Sanofi, Takeda and SunPharma. Linda Lévesque is now employed by Sanofi Pasteur, a global vaccine manufacturer; however, this study was completed before her employment at Sanofi Pasteur. No other competing interests were declared.

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