Quadrivalent human papillomavirus vaccine and autoimmune adverse events: a case–control assessment of the vaccine adverse event reporting system (VAERS) database

Abstract

Gardasil is a quadrivalent human papillomavirus (HPV4) vaccine that was approved for use by the US Food and Drug Administration in June 2006. HPV4 vaccine is routinely recommended for administration to women in the USA who are 11–12 years old by the Advisory Committee on Immunization Practices. Previous studies suggest HPV4 vaccine administration was associated with autoimmune diseases. As a consequence, an epidemiological assessment of the vaccine adverse event reporting system database was undertaken for adverse event reports associated with vaccines administered from 2006 to 2014 to 6–39 year-old recipients with a listed US residence and a specified female gender. Cases with the serious autoimmune adverse event (SAAE) outcomes of gastroenteritis (odds ratio (OR) 4.627, 95 % confidence interval (CI) 1.892–12.389), rheumatoid arthritis (OR 5.629, 95 % CI 2.809–12.039), thrombocytopenia (OR 2.178, 95 % CI 1.222–3.885), systemic lupus erythematosus (OR 7.626, 95 % CI 3.385–19.366), vasculitis (OR 3.420, 95 % CI 1.211–10.408), alopecia (OR 8.894, 95 % CI 6.255–12.914), CNS demyelinating conditions (OR 1.585, 95 % CI 1.129–2.213), ovarian damage (OR 14.961, 95 % CI 6.728–39.199), or irritable bowel syndrome (OR 10.021, 95 % CI 3.725–33.749) were significantly more likely than controls to have received HPV4 vaccine (median onset of initial symptoms ranged from 3 to 37 days post-HPV4 vaccination). Cases with the outcome of Guillain–Barre syndrome (OR 0.839, 95 % CI 0.601–1.145) were no more likely than controls to have received HPV4 vaccine. In addition, cases with the known HPV4-related outcome of syncope were significantly more likely than controls to have received HPV4 vaccine (OR 5.342, 95 % CI 4.942–5.777). Cases with the general health outcomes of infection (OR 0.765, 95 % CI 0.428–1.312), conjunctivitis (OR 1.010, 95 % CI 0.480–2.016), diarrhea (OR 0.927, 95 % CI 0.809–1.059), or pneumonia (OR 0.785, 95 % CI 0.481–1.246) were no more likely than controls to have received HPV4 vaccine. Confirmatory epidemiological studies in other databases should be undertaken and long-term clinical consequences of HPV-linked SAAEs should be examined.

Systematic review of factors associated with the development of Guillain–Barré syndrome 2007–2017: what has changed?

“…The two studies included in the review that analysed the association of HPV vaccine and GBS did not show any increased risk of developing the syndrome among the cases compared to the controls. The study populations were women aged 18-39 years and 6-39 years [40,41]. Similar results were found in France [50].…”

“…Campylobacter jejuni ( C. jejuni ), which is one of the leading factors associated with the development of GBS, was significantly associated with the development of GBS in all seven studies that studied this association . Pneumococcal vaccine, yellow fever and human papillomavirus (HPV) in girls were other vaccines reported in the studies; none were associated with the occurrence of GBS . Other aetiological agents studied that had statistically significant association with the occurrence of GBS included: M. pneumoniae (OR = 3.95 CI 95% 1.44–13.01), Epstein Barr virus [matched Odds Ratio (mOR) 20.0 CI 95% 1.81–220.56], acute hepatitis E infection (OR = 10.5 CI 95% 1.3–82.6), herpes zoster [Hazard ratio (HR) = 16.72 CI 95% 9.47–29.53], influenza [Incidence Risk Ratio (IRR) = 8.45 CI 95% 1.79–39.77], gastrointestinal infection (RR = 41.4 CI 95% 9.0–90.8), surgery (RR = 6.28 CI 95% 4.15–9.47) respiratory infection (OR = 4.57 IC 95% 1.55–13.4) and influenza‐like illness (RI = 7.35 CI 95% 4.36–12.38) .…”

“…Campylobacter jejuni (C. jejuni), which is one of the leading factors associated with the development of GBS, was significantly associated with the development of GBS in all seven studies that studied this association [33][34][35][36][37]. Pneumococcal vaccine, yellow fever and human papillomavirus (HPV) in girls were other vaccines reported in the studies; none were associated with the occurrence of GBS [38][39][40][41]. Other aetiological agents studied that had statistically significant association with the occurrence of GBS included: M. pneumoniae (OR = 3.95 CI 95% 38,39,[42][43][44][45].…”

Key genes and functional coexpression modules involved in the pathogenesis of systemic lupus erythematosus

“…There are also some observational studies on the link between virus infections and SLE (Hanlon, Avenell, Aucott, & Vickers, 2014;Rasmussen, Nielsen, Houen, & Jacobsen, 2016;Zandman-Goddard et al, 2009 Guiducci, & Coffman, 2007;Fagone, Muthumani, et al, 2014;Oon, Wilson, & Wicks, 2016). Some studies find that vaccinations against virus infections can also increase risk of SLE (Agmon-Levin et al, 2014;Geier & Geier, 2017;Wang, Shao, Wang, Xu, & Zhang, 2017), which further provides some evidence for et al, 1996;Gröndal et al, 2000). Its important role is also evidenced in our study.…”

Role of environmental factors in autoimmunity: pearls from the 10th international Congress on autoimmunity, Leipzig, Germany 2016

“…Geier and Geier [22], who performed a review of cases with the serious autoimmune adverse event outcomes of the VAERS database, performed another huge work. They observed that adverse events in terms of gastroenteritis, rheumatoid arthritis, thrombocytopenia, systemic lupus erythematosus, vasculitis, alopecia, CNS demyelinating conditions, ovarian damage, and irritable bowel syndrome were associated with the quadrivalent HPV vaccine administration.…”