Systematic causality assessment of adverse events following HPV vaccines: Analysis of current data from Apulia region (Italy)

Since 2013, World Health Organization (WHO) recommended that adverse events following immunization (AEFIs) should be evaluated by a standardized algorithm for causality assessment, however the use of WHO procedure is rarely adopted. In Italy, AEFIs (classified only by temporal criteria) are registered in the National Drug Authority (AIFA) database, but causality assessment is not mandatory. Every year AIFA publishes the AEFIs report, that doesn't contain information about causal correlation between events and vaccines. From AIFA database, we selected AEFIs following human papillomavirus vaccination (HPV) reported in Apulia (about 4,000,000 inhabitants) during 2008-2016. For serious AEFIs, we applied WHO causality assessment criteria; for cases hospitalized, we repeated the assessment getting additional information from health documentation. In 2008-2016, 100 HPV AEFIs (reporting rate: 17.8 per 100,000 doses) were registered of which 19 were serious (rate: 3.4 per 100,000 doses) and 12 led to hospitalization. After causality assessment, for 9 AEFIs the classification was "consistent causal association to immunization", for 3 indeterminate, for 5 "inconsistent causal association to immunization" and for 2 not-classifiable. Among hospitalized patients, 5 AEFIs were consistent, 5 inconsistent, 1 not-classifiable and 1 indeterminate; adding information from health documentation, the results were similar except for indeterminate and not classifiable AEFIs that turned into "not consistent". Only half of severe AEFIs could be associated with vaccination and this suggests that AIFA report provides a incomplete picture of HPV vaccine safety, with a risk for readers to confound "post hoc" and "propter hoc" approach without considering the causality assessment results. In the view of the systematic use of WHO causality assessment algorithm in the AEFI surveillance, the efforts of Public Health must be focused on the improvement of the quality of the information provided to reduce conclusions inter-observer variability; the routine follow-up of reports, also to collect additional information, must be guaranteed.