The association of adverse events with bivalent human papilloma virus vaccination: A nationwide register-based cohort study in Finland (CFS looked at)

[Dolphin]

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https://www.sciencedirect.com/science/article/pii/S0264410X18309253

Vaccine
Available online 13 August 2018


The association of adverse events with bivalent human papilloma virus vaccination: A nationwide register-based cohort study in Finland

Highlights


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Large nation-wide cohort study on safety of bivalent human papillomavirus vaccine.

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The association of vaccination was evaluated for 38 selected diseases/syndromes.

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The risk was not higher after human papillomavirus vaccination for any diseases.

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Study provides reassuring results regarding adverse events following HPV vaccination.



Abstract
Background
A bivalent HPV vaccine (Cervarix®; HPV2, GlaxoSmithKline) was introduced into the Finnish national vaccination programme (NVP) in November 2013 for girls aged 11–13 years with a catch-up for 14–15 year-olds. We evaluated the association between HPV2 and selected autoimmune diseases and clinical syndromes by conducting a nation-wide retrospective register-based cohort study.

Methods
First life-time occurrences of the relevant ICD-10 codes in girls aged 11–15 years between Nov-2013 and Dec-2016 were obtained from the national hospital discharge register. Population denominators were obtained from the Population Information System and vaccination records from the National Vaccination Register. Registers were linked using unique personal identity codes. Association between HPV2 and 38 selected outcomes were studied using Cox regression, with age as the main time-scale and the first vaccination dose as the time-dependent exposure. The hazard ratios (HR) with 95%CI were assessed according to the time since exposure (entire follow-up, 0-180/181-365/>365 days).

Results
Of 240 605 girls eligible for HPV2 vaccination, 134 615 (56%) were vaccinated. After adjustment for geographical area (6 hospital districts), country of origin (Finnish-born/not) and number of hospital contacts from 9 through 10 years of age, HRs ranged from 0.34 (95%CI 0.11–1.05) to 8.37 (95%CI 0.85–82.54) and HPV2 vaccination was not statistically significantly associated with a higher risk of any outcome during the entire follow-up.

Conclusions
This study found no significantly increased risk for the selected outcomes after the HPV vaccination in girls 11–15 years of age. These results provide valid evidence to counterbalance public scepticism, fears of adverse events and possible opposition to HPV vaccination and consequently can contribute to increase HPV vaccination coverage in Finland as well as elsewhere.

 

[Dolphin]

There were in total 4 outcomes for which the adjusted HR was statistically significantly below one for the overall period (CFS/SEID, epilepsy and recurrent seizures, Henoch-Schonleińs purpura, malaise/fatigue)

Some studies reported association of HPV vaccines with the CFS/SEID [2], [32], CRPS [33] and POTS [2], [32], [33], [34], while others, in line with our results, did not [35], [36], [37]. The CFS/SEID was negatively associated with the HPV2 in our study.

 

[Snow Leopard]

The HR of 5.31 shows a trend towards a risk for Guillain-Barré syndrome. Note that this is a relatively rare consequence (around 1/100,000 person-doses reported in other studies of vaccines) and this study simply does not have the statistical power to detect events of that frequency with statistical significance.