No evidence found for an increased risk of long-term fatigue following human papillomavirus vaccination of adolescent girls.

Abstract

INTRODUCTION: In 2013, the Netherlands Pharmacovigilance Center Lareb published an overview of reports of long-lasting fatigue following bivalent HPV-vaccination  (2vHPV). After an update of this overview in 2015, concerns regarding the safety  of 2vHPV was picked up by the media, which led to further reports of long-lasting  fatigue. Therefore, the Dutch National Institute for Public Health and the  Environment (RIVM) investigated a possible association between HPV-vaccination  and long-term fatigue. METHODS: In this retrospective cohort study conducted in  the Integrated Primary Care Information database, we investigated the occurrence  of chronic fatigue syndrome (CFS), fatigue ≥6 months and 3-6 months in all girls  born in 1991-2000 during the follow-up period January 1st 2007-December 31st 2014  (2007-2008 pre-vaccination and 2009-2014 post-vaccination). Patients with certain  fatigue ≥6 m were asked for consent to link their primary care information with  vaccination data. Incidence rates per 10,000 person years (PY) for 12-16-year-old  girls were compared between pre- and post-HPV-vaccine era. A self-controlled case  series (SCCS) analysis was performed using consenting vaccinated cases. A primary  high-risk period of 12 months after each dose was defined. RESULTS: The cohort  consisted of 69,429 12-16-year-old girls accounting for 2758 PY pre-vaccination  and 57,214 PY post-vaccination. Differences between pre- and post-vaccination  incidences (CFS: 3.6 (95% CI 0.5-25.7)/10,000 PY and 0.9 (0.4-2.1); certain  fatigue ≥6 m: 7.3 (1.8-29.0) and 19.4 (16.1-23.4); certain fatigue 3-6 m: 0.0 and  16.6 (13.6-20.3), respectively) were not statistically significant. SCCS analyses  in 16 consenting vaccinated cases resulted in an age-adjusted RR of 0.62 (95%CI  0.07-5.49). CONCLUSIONS: Fatigue ≥6 m and 3-6 m was frequently found among  adolescent girls, but CFS was rarely diagnosed. No statistically significant  increased incidence rates were found post-vaccination compared to similar age  groups of girls pre-vaccination. The SCCS analysis included a low number of cases  but revealed no elevated risk of certain fatigue ≥6 m in the high-risk period.