Assessment of thyroiditis risk associated with HPV vaccination among girls aged 9-18 years: A time-varying cohort study

Belén Castillo-Cano; Mar Martín-Pérez; Ana Llorente-García; Dolores Montero-Corominas; Marc Comas-Cufí; Elisa Martín-Merino

doi:10.1016/j.vaccine.2022.06.060

Assessment of thyroiditis risk associated with HPV vaccination among girls aged 9-18 years: A time-varying cohort study

Vaccine. 2022 Aug 5;40(33):4816-4826. doi: 10.1016/j.vaccine.2022.06.060. Epub 2022 Jul 2.

Authors

Belén Castillo-Cano¹, Mar Martín-Pérez¹, Ana Llorente-García¹, Dolores Montero-Corominas¹, Marc Comas-Cufí², Elisa Martín-Merino³

Affiliations

¹ Division of Pharmacoepidemiology and Pharmacovigilance. Spanish Agency of Medicines and Medical Devices (AEMPS), 28022, Madrid, Spain.
² Department of Computer Science, Applied Mathematics and Statistics, University of Girona, Girona, Spain.
³ Division of Pharmacoepidemiology and Pharmacovigilance. Spanish Agency of Medicines and Medical Devices (AEMPS), 28022, Madrid, Spain. Electronic address: emartinm@aemps.es.

PMID: 35792023
DOI: 10.1016/j.vaccine.2022.06.060

Abstract

Background: Previous studies have suggested a relationship between human papillomavirus vaccine and autoimmune diseases, including thyroiditis. Thus, we aimed to evaluate the risk of thyroiditis associated with HPV vaccination among girls using the Primary Care Database For Pharmacoepidemiological Research (BIFAP) in Spain.

Methods: In this retrospective cohort study, girls in BIFAP aged 9-18 years from 2007 to 2016, free of past thyroiditis and HPV vaccination, were included. Hazard Ratios (HRs; 95% CI) of thyroiditis were calculated within exposed periods (up to 2 years of vaccination) and post-exposed periods (from 2 years after vaccination onwards) compared with non-exposed periods, overall, by dose and by type of vaccine, adjusted for potential confounders collected at different times. In a post-hoc analysis, we moved back the thyroiditis date (30 days) as a theoretical delay in diagnosis.

Results: Out of the 388,411 girls included in the cohort, 153,924 were vaccinated against HPV and 480 thyroiditis (253 autoimmune) cases were identified (334 non-exposed; 103 exposed; 43 post-exposed). Adjusted HR was 1.18 [95% CI: 0.79-1.76] for exposed (1.25 [0.77-2.04] for bi- and 1.15 [0.76-1.76] for quadri-valent vaccines) and 1.26 [0.74-2.14] for post-exposed periods. HR was 1.50 [0.87-2.59] for the 1^st dose, 1.13 [0.66-1.91] for the 2^nd and 1.11 [0.71-1.72] for the 3^rd one. When the diagnosis date was moved back, the risk was 1.14 [0.76-1.70] for exposed period, being 1.80 [0.86-3.76] and 1.40 [0.74-2.66] after 1^st dose of bi- and quadri-valent, respectively.

Conclusions: We did not observe an increased risk of thyroiditis following HPV vaccination (whether bi- or quadri-valent). Even though the point estimate was higher after 1^st HPV vaccination dose than after subsequent doses, a dose-effect was not confirmed. Results remained similar after applying a lag time.

Keywords: Girls; Hazard Ratio; Human papillomavirus vaccination; Paediatrics; Primary care; Thyroiditis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
Female
Humans
Papillomavirus Infections* / epidemiology
Papillomavirus Infections* / prevention & control
Papillomavirus Vaccines* / adverse effects
Retrospective Studies
Thyroiditis* / chemically induced
Thyroiditis* / epidemiology
Uterine Cervical Neoplasms* / prevention & control
Vaccination / adverse effects

Substances

Papillomavirus Vaccines