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. 2022 Nov 11;8(11):e11515.
doi: 10.1016/j.heliyon.2022.e11515. eCollection 2022 Nov.

OAE-based data mining and modeling analysis of adverse events associated with three licensed HPV vaccines

Wenrui Zi  1 , Qiuyue Yang  1 , Jun Su  1 , Yongqun He  2 , Jiangan Xie  1
Affiliations

OAE-based data mining and modeling analysis of adverse events associated with three licensed HPV vaccines

Wenrui Zi et al. Heliyon. .

Abstract

Purpose: Three licensed human papillomavirus (HPV) vaccines (Cervarix, Gardasil, and Gardasil 9) have been effectively used to prevent infection with oncogenic HPV types; however, many adverse events (AEs) have also been reported following their vaccinations. We assessed AE profiles after receiving the HPV vaccines based on the reported data from Vaccine Adverse Event Reporting System (VAERS).

Methods: The AE data associated with Cervarix, Gardasil, and Gardasil 9 were retrieved from VAERS database respectively. The combinatorial biomedical statistical methods were used to identify the statistically significant AEs. The Gamma-Poisson Shrinker (GPS) model with gender/age stratification was applied to ascertain the serious adverse events (SAEs) related to the three licensed HPV vaccines. The AE profiles were classified and represented by the Ontology of Adverse Events (OAE) for further analysis.

Results: As of July 31, 2020, VAERS recorded 3,112, 31,606, and 6,872 AE case reports for Cervarix, Gardasil, and Gardasil 9, respectively. Our Frequentist statistical methods identified 135 Cervarix-enriched AEs, 55 Gardasil-enriched AEs, and 17 Gardasil 9-enriched AEs. Based on the OAE hierarchical classification, these AEs were clustered in the AEs related to behavioral and neurological conditions, immune system, nervous system, and reproductive system. Combined with GPS modeling, 46 unique statistically significant SAEs were founded to be associated with at least one of the three vaccines.

Conclusions: Our study led to the better understanding of the AEs associated with the licensed HPV vaccines. The hypotheses on the cause and effect relationships between the HPV vaccination and specific AEs deserve further epidemiological investigations as well as clinical trial studies.

Keywords: Adverse event; Gamma-Poisson shrinker; Human papillomavirus; Ontology of adverse events; Vaccine; Vaccine adverse event reporting system (VAERS).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overall project workflow. VAERS: Vaccine Adverse Event Reporting System; AE: adverse event; SAE: serious adverse event; HPV: human papillomavirus; GPS: Gamma-Poisson Shrinker; MedDRA: Medical Dictionary for Regulatory Activities; OAE: Ontology of Adverse Events.
Figure 2
Figure 2
The SAE with stronger association with the HPV vaccines comparing to the other vaccines in VAERS. (a) The vaccine-postural orthostatic tachycardia syndrome EB05 scores on entire dataset in gender stratification. (b) The vaccine-amenorrhoea EB05 scores on entire dataset in gender stratification. (c) The vaccine-premature menopause EB05 scores on entire dataset in gender stratification. (d) The vaccine-metrorrhagia EB05 scores on entire dataset in gender stratification. (e) The vaccine-autoimmune encephalopathy EB05 scores on entire dataset in gender stratification. (f) The vaccine-autoimmune encephalitis EB05 scores on entire dataset in gender stratification. (g) The vaccine-juvenile idiopathic arthritis EB05 scores on entire dataset in gender stratification. (h) The vaccine-juvenile idiopathic arthritis EB05 scores on entire dataset in age stratification. (i) The vaccine-autoimmune encephalopathy EB05 scores on entire dataset in age stratification.
Figure S1
Figure S1
Classification of statistically significant AEs associated with Gardasil and Gardasil 9 in females and males based on the Ontology of Adverse Events (OAE). (a) The OAE classification hierarchy for the AEs associated with Gardasil. (b) The OAE classification hierarchy for the AEs associated with Gardasil 9. F represents the AE that occurred in females. M represents the AE that occurred in males. FM represents the AE that occurred in females as well as in males.
Figure S2
Figure S2
Classification of 46 SAEs associated with the three HPV vaccines using the Ontology of Adverse Events (OAE).
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