OAE-Based Data Mining And Modeling Analysis Of Adverse Events Associated With The Licensed HPV Vaccines

Three licensed human papillomavirus(HPV)vaccines(Cervarix,Gardasil,and Gardasil 9)are widely administered to the suitable population.HPV vaccines have been effectively used to prevent infection with oncogenic HPV types;however,many adverse events(AEs)have also been reported following their vaccinations,some are serious and even fatal.We assessed AE profiles after receiving the HPV vaccines based on the reported data from Vaccine Adverse Event Reporting System(VAERS).First of all,The AE data associated with Cervarix,Gardasil,and Gardasil 9 were retrieved from VAERS database,respectively.Then,the combinatorial biomedical statistical methods including Proportional Reporting Ratio(PRR),Chi-square test(X~2),and Base Level Filtration(BLF)were used to identify the statistically significant AEs.Furthermore,The Gamma-Poisson Shrinker(GPS)model with gender/age stratification was used to ascertain the serious adverse events(SAEs)related to the three licensed HPV vaccines.Finally,The AE profiles were classified and represented by the Ontology of Adverse Events(OAE)for further analysis.The main results are as following:1.As of 2020,VAERS recorded 3131,31691,and 7432 AE case reports for Cervarix,Gardasil,and Gardasil 9,respectively.Our Frequentist statistical methods identified 148Cervarix-enriched AEs,54 Gardasil-enriched AEs,and 16 Gardasil 9-enriched AEs.Based on the OAE hierarchical classification,these AEs were clustered in the AEs related to behavioral and neurological AE.2.The thesis also mined 52 and 19 Gardasil-enriched AEs,15 and 19 Gardasil 9-enriched AEs in female and male.Based on the OAE adverse event profiles,digestive system AEs and reproductive system AEs were more common in female than male recipients after Gardasil vaccination.For Gardasil 9,the injection-site AE symptoms(e.g.,injection-site hypoaesthesia)were more common experienced by males.In addition,people aged group of 27-45 after vaccination with Gardasil 9,most of AE profile were mild and with rare SAEs.3.Based on GPS modeling analysis,comparing with the Frequentist statistical methods,59 SAEs were identified to be associated with at least one of the three HPV vaccines.And these SAEs were enriched in the categories of behavioral and neurological AE,immune system AE,nervous system AE,and reproductive system AE.In our study,scientific data mining and modeling analysis of adverse events associated with the licensed HPV vaccines based on OAE to find scientific knowledges among‘vaccine-AE-immunizer’,which help us better understand the association between AEs and HPV vaccines.The hypotheses on the cause and effect relationships between the HPV vaccination and specific SAEs deserve further epidemiological investigations as well as clinical trial studies.