As part of its missions of medicines and health product safety monitoring, the ANSM (French National Agency for Medicines and Health Products Safety) has carried out a pharmaco-epidemiological study in collaboration with CNAMTS (French National Health Insurance Fund for Salaried Workers) on the safety of HPV vaccination based on analysis of the French healthcare administrative databases. This study constitutes one of the components of the national and international vaccine monitoring strategy, in addition to the European risk management plan and national enhanced pharmacovigilance monitoring. It was specifically designed to investigate a potential link between HPV vaccination and the development of autoimmune disease.
All girls aged 13 to 16 years between 2008 and 2012, covered by the French general health insurance scheme and without history of HPV vaccination nor AID, were included and followed using French nationwide databases. Fourteen neurological, rheumatological, haematological, gastrointestinal or endocrine AID, were identified from hospital stays, long-term illnesses or marker drugs. Their incidence was compared between girls exposed versus non-exposed to HPV vaccination, using a Cox model adjusted for inclusion year, geographical area, socio-economic indicators, healthcare use level and other immunizations.
A total of 2,252,716 girls were included. During a mean follow-up time of 33 months, 37% received HPV vaccine and 4,096 AID occurred. Exposure to HPV vaccination was not associated with the occurrence of 12 out of the 14 studied AID. HPV vaccination was strongly associated with an increased risk of Guillain-Barré syndrome (GBS): incidence rate of 1.36 among the exposed [19 cases] versus 0.37 per 100 000 PY among the unexposed [21 cases]; adjusted HR: 3.96 [95%CI: 1.82 to 8.61]. This association was robust and particularly marked in the first months following vaccination. Under the hypothesis of a causal relationship, this would result in 1.8 GBS cases attributable to HPV vaccine per 100,000 girls vaccinated. A weak association between HPV vaccination and incidence of IBD was found (adjusted HR: 1.18 [95% CI: 1.01 to 1.38]), which became non-significant after censoring the first three months following vaccination.
This study provides reassuring results with respect to the risk of AID after HPV vaccination, confirming the results of previous epidemiological studies. An increased risk of GBS after HPV vaccination seems likely; nevertheless, this increased risk, if confirmed, would have a limited public health impact. Results do not support a causal association between HPV vaccine and IBD.