A large cohort study found no concerning safety issues associated with the use of human papillomavirus (HPV) vaccine in adult women. There was an increased rate of celiac disease, but this may be related to general underdiagnosis of the condition and its unmasking at vaccination visits.
“This is the most comprehensive study of HPV vaccination in adult women to date,” said Anders Hviid, MSc, DMSc, of the Statens Serum Institut in Copenhagen, in a press release. “It is not unreasonable to expect different safety concerns in adult women compared with young girls, and our study is an important supplement to the safety studies in young girls.”
As Hviid noted, most safety data on available HPV vaccines are in the target population of younger individuals. The new study included 3,126,790 women aged 18 to 44 years included in Danish (38% of the total) and Swedish (62%) registries. Vaccine uptake was 8% overall—18% in the Danish women and 2% in the Swedish women. They were followed for 16,386,459 person-years, looking at incidences of 45 preselected serious chronic diseases; the results were published online ahead of print in the Journal of Internal Medicine.
The analysis found seven adverse events (AEs) with significantly increased rate ratios (RRs) associated with the quadrivalent HPV vaccine, and four AEs with significantly reduced incidence. The increased RRs included Hashimoto thyroiditis, celiac disease, localized lupus erythematosus, pemphigus vulgaris, Addison disease, Raynaud disease, and encephalitis, myelitis, or encephalomyelitis. The AEs with reduced incidence included paralysis, Grave disease, hypothyroidism, and Bell palsy.
After a series of sensitivity analyses and adjustments, only celiac disease maintained the positive association. The RR for celiac disease was 1.56 (95% CI, 1.29–1.89) for any time following vaccination; using a self-controlled case series method to account for other confounders, the RR was 1.65 (95% CI, 1.20–2.27). The association appeared stronger in the Danish cohort (RR, 1.74; 95% CI, 1.35–2.25) than in the Swedish population (RR, 1.21; 95% CI, 0.87–1.68).
“Unmasking of pre-existing conditions at vaccination visits has been described for adolescents and young adults in the context of quadrivalent HPV vaccination; the vaccination visit triggers a work-up of symptoms that later result in a diagnosis,” the authors wrote. “Unmasking of an underreported disease such as celiac disease in quadrivalent HPV-vaccinated Danish women is a possible explanation for the increased RR.”
They concluded that these results generally do not raise any safety issues of concern regarding the use of the HPV vaccine in adult women.