Evaluation of the Risk of Inflammatory Bowel Disease after the HPV Vaccination in Primary Care in Spain: A Time-Varying Cohort Analysis of Around 390,000 Girls
- 19 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Drug Safety
- Vol. 44 (4), 455-466
- https://doi.org/10.1007/s40264-020-01040-0
Abstract
Introduction A link between the human papillomavirus vaccination (HPVv) and inflammatory bowel disease (IBD) has been suggested. Objective We aimed to estimate the risk of IBD following HPVv compared with periods not exposed to the vaccines. Methods Primary healthcare records (Spanish Primary Care Database For Pharmacoepidemiological Research [BIFAP]) were used in a cohort study of girls in Spain aged 9–18 years between 2007 and 2016 free of IBD or HPVv at study entrance. During the follow-up to IBD diagnosis, time-varying HPVv exposure and confounders were assessed in Cox models to estimate the hazard ratio (HRs) of IBD in the 2 years after HPVv (exposed period) and thereafter (post-exposed) compared with the no exposure periods. In a post hoc analysis, we moved the IBD date back 30 days as a theoretical delay in diagnosis confirmation. Results The cohort comprised 388,669 girls; 154,174 of these received the HPVv, and 88 IBD cases occurred (55 non-exposed, 22 exposed [after first N = 6, second N = 2, or third N = 14 dose] and 11 in post-exposed periods). The adjusted HR was 1.66 (95% confidence interval [CI] 0.68–4.05) for exposed and 1.10 (95% CI 0.37–3.24) for post-exposed periods. The HR for the first dose was 3.94 (95% CI 1.19–13.02). No association was found for the second or third doses. Post hoc, the HR was 1.83 (95% CI 0.72–4.69) for exposed periods (N = 18), and 1.84 (95% CI 0.35–9.83; N = 2), 1.50 (95% CI 0.40–5.63; N = 4) and 1.98 (95% CI 0.71–5.49; N = 12) after the first, second and third doses, respectively. Conclusions This study did not show an increased risk of IBD following 2 years of HPVv exposure. However, an increased risk of IBD diagnosis was observed following the first vaccination dose (1–34 days), which is likely attributable to the clinical recommendation to vaccinate upon onset of IBD symptoms.Keywords
Funding Information
- Instituto de Salud Carlos III (PI17/02300)
This publication has 13 references indexed in Scilit:
- The Longitudinal Incidence of Human Papillomavirus Vaccination in Spanish Primary Care in the First 10 Years After ApprovalPharmaceutical Medicine, 2019
- Graphical Depiction of Longitudinal Study Designs in Health Care DatabasesAnnals of Internal Medicine, 2019
- The recording of human papillomavirus (HPV) vaccination in BIFAP primary care database: A validation studyPharmacoepidemiology and Drug Safety, 2018
- The impact of different strategies to handle missing data on both precision and bias in a drug safety study: a multidatabase multinational population-based cohort studyClinical Epidemiology, 2018
- Human papillomavirus vaccination and risk of autoimmune diseases: A large cohort study of over 2 million young girls in FranceVaccine, 2017
- Inflammatory Bowel Disease and Cervical Neoplasia: A Population-Based Nationwide Cohort StudyClinical Gastroenterology and Hepatology, 2015
- Family history of inflammatory bowel disease among patients with ulcerative colitis: A systematic review and meta-analysisJournal of Crohn's and Colitis, 2014
- Cancer Risk in Inflammatory Bowel Disease According to Patient Phenotype and Treatment: A Danish Population-Based Cohort StudyThe American Journal of Gastroenterology, 2013
- Cancer in patients with ulcerative colitis, Crohnʼs disease and coeliac disease: record linkage studyEuropean Journal of Gastroenterology & Hepatology, 2008
- Paramyxovirus infections in childhood and subsequent inflammatory bowel diseaseGastroenterology, 1999