Human papillomavirus vaccination and risk of autoimmune diseases: A large cohort study of over 2million young girls in France

Abstract

Background: Whether human papillomavirus (HPV) vaccination could induce or trigger autoimmune diseases (AID) has been questioned, and potentially contributes to low immunization coverage in France. This study evaluated the association between HPV vaccination and the risk of AID using routinely collected data sources.

Methods: All girls aged 13-16years between 2008 and 2012, covered by the general health insurance scheme and without history of HPV vaccination or AID, were included and followed using French nationwide databases. Fourteen neurological, rheumatological, haematological, gastrointestinal or endocrine AID, were identified from ICD-10 codes allocated to hospital stays and long-term illnesses or by marker drugs. Their incidence was compared between girls exposed and non-exposed to HPV vaccination, using a Cox model adjusted for inclusion year, geographic area, socio-economic indicators, healthcare use level and other immunizations.

Results: Among 2,252,716 girls, 37% received HPV vaccine and 4,096 AID occurred during a mean follow-up time of 33months. The incidence of AID was not increased after exposure to HPV vaccination, except for Guillain-Barré syndrome (GBS) (incidence rate of 1.4 among exposed [20 cases] versus 0.4 per 100,000 PY among unexposed [23 cases]; adjusted HR: 3.78 [1.79-7.98]). This association persisted across numerous sensitivity analyses and was particularly marked in the first months following vaccination. Under the hypothesis of a causal relationship, this would result in 1-2 GBS cases attributable to HPV vaccine per 100,000 girls vaccinated.

Conclusions: Our study provides reassuring results regarding the risk of AID after HPV vaccination, but an apparently increased risk of GBS was detected. Further studies are warranted to confirm this finding.

Keywords: Autoimmune diseases; Cohort; France; Human papillomavirus vaccine; National database; Pharmacoepidemiology.