Vaccination has been suggested in the aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). However, for the vaccines studied, including the bivalent HPV vaccine, no associations have been found [1, 6-9]. The risk of developing CFS/ME after vaccination with the quadrivalent HPV-vaccine has not been studied. Recently, an increased risk of two syndromes with symptoms that partly overlap with CFS/ME (postural orthostatic tachycardia syndrome and complex regional pain syndrome) after HPV vaccination has been suspected [10-12]. From 2009, quadrivalent HPV vaccine has been offered to 12 year old girls in the Norwegian Childhood Immunisation Programme. We studied whether HPV vaccination was associated with risk of CFS/ME and assessed medical history in relation to both risk of CFS/ME and HPV vaccine uptake. Uptake of at least one dose increased from 70% to 88 % in the study period, 2009-2014.
We linked individual data from national registries, including the population registry, the patient registry and the immunisation registry using the unique personal identification number.
Yearly incidence rates of CFS/ME for 2009–2014 were calculated among all boys and girls, aged 10–17 living in Norway during the period, n=824,133.
Girls born 1997–2002 were eligible for HPV vaccination and included in analyses of the interplay between vaccination, medical history and CFS/ME, n=176,453.
We calcutaled hazard ratios (HRs) of CFS/ME using Cox regression. Risk differences (RDs) of vaccine uptake were calculated with binomial regression.
Although the incidence of CFS/ME was higher among girls than boys, we observed a similar yearly increase in incidence rate of CFS/ME among girls and boys,
Among girls eligible for HPV vaccination, the risk of CFS/ME increased with increasing number of previous hospital visits, HR=5.23 (95% CI 3.66–7.49) for seven or more visits as compared to no visits. Having seven or more hospital visits was associated with a lower HPV vaccine uptake, RD=-5.5% (95% CI -6.7%–-4.2%).
We observed no association between HPV vaccination and risk of CFS/ME, HR=0.86 (95% CI 0.69–1.08) for the entire follow-up period and 0.96 (95% CI 0.64–1.43) for the first two years after vaccination.
We observed an increase in CFS/ME incidence during 2009–2014. The increase was similar in girls and boys.
Further, an association between medical history and risk of CFS/ME was observed, and the risk increased with increasing number of hospital visits.
Analysing individual data, no indication of increased risk of CFS/ME following HPV vaccination was found among 176,453 girls offered HPV vaccine through the national immunisation programme in Norway 2009-2014.
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