Evaluation of the safety profile of the quadrivalent vaccine against human papillomavirus in the risk of developing autoimmune, neurological, and hematological diseases in adolescent women in Colombia

Background: Cervical cancer eradication is one of the main goals for 2030 by the World Health Organization, which can only be achieved with high vaccination rates against Human Papilloma Virus. In Colombia, more and better scientific evidence is required to increase confidence in vaccination. The objective of this study is to evaluate the safety profile of the quadrivalent vaccine against HPV in the risk of developing autoimmune, neurological, and hematological diseases in adolescent women in Colombia. Methods: We designed a cohort study based on national HPV vaccination records and incident diagnostic data for the diseases of special interest during 2012 and 2021. We included adolescent women between 9 and 19 years old and compared vaccinated and non -vaccinated cohorts using an Inverse Probability of Treatment Weighting (IPWT) method for each scenario disease and follow-up period (180 and 360 days). Findings: The Odds Ratio (OR) of developing diseases of interest was estimated during two follow up periods, 180 and 360 days after the follow-up index date (Vaccination Day). The OR for developing rheumatoid arthritis was 4.4; CI95% (1.74 - 11.14), juvenile idiopathic arthritis was 2.76 IC95% (1.50 - 5.11), idiopathic thrombocytopenic purpura was 2.54 IC95% (1.28 - 5.02) and thyrotoxicosis was 2.86 IC95% (1.03 - 7.95), when comparing the vaccinated versus unvaccinated population. However, the temporal distribution of cases incident did not reveal a clear difference between the cohorts, since the rate of appearance of new cases has a constant linear behavior for the two groups. Interpretation: For rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic thrombocytopenic purpura, and thyrotoxicosis; the application of the vaccine had an effect on the development of the disease. Nevertheless, our results should be interpreted with caution and be further studied, considering that the biological plausibility of the events occurred without a clear temporal pattern in relation to the exposure to the vaccine.