WHO recommends that serious adverse events following immunization (AEFIs) should be monitored and evaluated using a standardized algorithm for causality assessment. “Per protocol”, after a comprehensive analysis of the event and the concomitant factors, the relationship between the vaccine and the AEFI could be classified as “consistent”, “not consistent”, “undetermined” or “unclassifiable” (1). Despite WHO recommendations, the AEFI causality assessment manual is, in the clinical practice, rarely adopted. In Italy, AEFIs, spontaneously reported from physicians, healthcare workers or patients to the National Drug Authority (AIFA) routine surveillance system, are classified only by temporal criteria. Therefore, the AEFIs report, published yearly by the AIFA, lacks information about the strength of correlation between events and vaccines (2). In this work, we aimed at evaluating the systematic use of Causality Assessment algorithm of AEFIs following HPV vaccination in Italy.
In the Apulia region of Italy (about 4,000,000 inhabitants), from 2008 to 2014, 438,294 HPV vaccine doses were administered to females aged 12, 18 and 25 years. We selected severe AEFIs following HPV vaccination reported between 2008 and 2014 to the AIFA routine surveillance system. We applied the WHO causality assessment criteria; for AEFIs requiring hospitalization, we repeated the assessment obtaining additional information from individual medical records.
Of 14 severe AEFIs following HPV vaccination (reporting rate: 3.2 x100,000 doses), 8 (57.1%) led to hospital admission. After causality assessment, 7 AEFIs were classified as consistent, 3 undetermined, 2 not consistent, 2 unclassifiable. Among hospitalized cases, 4 AEFIs were classified as consistent, 2 as not consistent, 1 as undetermined and 1 as unclassifiable; adding information from medical records, we obtained similar outcomes with the exception of the “undetermined” AEFI that changed in “not consistent”.
Severe AEFIs following HPV vaccination are rare. The systematic use of the causality assessment algorithm showed that only half of them could be related to vaccination. Information from the AIFA routine surveillance system, in the absence of a causative analysis, provides a distorted picture of the HPV vaccine safety and should be interpreted with caution.
1. WHO. Causality Assessment of an Adverse Event Following Immunization (AEFI), User 
manual for the revised WHO classification. WHO/HIS/EMP/QSS. March 2013
2. National Drug Authority (AIFA). Rapporto sulla sorveglianza postmarketing dei vaccini in Italia Anno 2013. Available from: http://www.agenziafarmaco.gov.it/sites/default/files/RapportoVaccini2013.pdf