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Systematic Review Open Access
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Abstract

Background

Guillain–Barré syndrome (GBS) is a rare autoimmune disease that can follow viral infections and has in a few cases been linked to vaccinations. Pre-licensure clinical trials did not observe an association between human papillomavirus (HPV) vaccination and GBS, a post-marketing study from 2017 reported an increased relative risk.

Aim

We assessed the risk of GBS after HPV vaccination through a systematic literature review and meta-analysis.

Methods

We searched Embase, MEDLINE and Cochrane for studies reporting on the risk of GBS after HPV vaccination in individuals aged ≥ 9 years, published between 1 January 2000 and 4 April 2020, excluding studies without a comparator group. Seven studies reporting relative effect sizes were pooled using random-effects meta-analysis. We assessed quality of evidence using the GRADE approach. Study protocol was registered (PROSPERO No. #CRD42019123533).

Results

Of 602 identified records, we included 25 studies. Based on over 10 million reports, cases of GBS were rare. In 22 studies no increased risk was observed, while in three studies a signal of increased risk of GBS after HPV vaccination was identified. Meta-analysis yielded a pooled random-effects ratio of 1.21 (95% CI: 0.60–2.43); I2 = 72% (95% CI: 36–88). This translates to a number needed to harm of one million to be vaccinated to generate one GBS case. Quality of evidence was very low.

Conclusions

The absolute and relative risk of GBS after HPV vaccination is very low and lacks statistical significance. This is reassuring for the already implemented vaccination programmes and should be used in respective communication activities.

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2022-01-27
2022-05-23
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2022.27.4.2001619
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References

  1. Harder T, Wichmann O, Klug SJ, van der Sande MAB, Wiese-Posselt M. Efficacy, effectiveness and safety of vaccination against human papillomavirus in males: a systematic review. BMC Med. 2018;16(1):110.  https://doi.org/10.1186/s12916-018-1098-3  PMID: 30016957 
  2. Schiller JT, Castellsagué X, Garland SM. A review of clinical trials of human papillomavirus prophylactic vaccines. Vaccine. 2012;30(Suppl 5):F123-38.  https://doi.org/10.1016/j.vaccine.2012.04.108  PMID: 23199956 
  3. Drolet M, Bénard É, Pérez N, Brisson M, Ali H, Boily M-C, et al. Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis. Lancet. 2019;394(10197):497-509.  https://doi.org/10.1016/S0140-6736(19)30298-3  PMID: 31255301 
  4. Sha BE. Adult immunization update. JAMA. 2019;322(11):1096-7.  https://doi.org/10.1001/jama.2019.12739  PMID: 31424523 
  5. Palmer T, Wallace L, Pollock KG, Cuschieri K, Robertson C, Kavanagh K, et al. Prevalence of cervical disease at age 20 after immunisation with bivalent HPV vaccine at age 12-13 in Scotland: retrospective population study. BMJ. 2019;365:l1161.  https://doi.org/10.1136/bmj.l1161  PMID: 30944092 
  6. Patel EU, Grabowski MK, Eisenberg AL, Packman ZR, Gravitt PE, Tobian AAR. Increases in Human Papillomavirus vaccination among adolescent and young adult males in the United States, 2011-2016. J Infect Dis. 2018;218(1):109-13.  https://doi.org/10.1093/infdis/jiy165  PMID: 29584878 
  7. Bruni L, Diaz M, Barrionuevo-Rosas L, Herrero R, Bray F, Bosch FX, et al. Global estimates of human papillomavirus vaccination coverage by region and income level: a pooled analysis. Lancet Glob Health. 2016;4(7):e453-63.  https://doi.org/10.1016/S2214-109X(16)30099-7  PMID: 27340003 
  8. DeStefano F, Bodenstab HM, Offit PA. Principal controversies in vaccine safety in the United States. Clin Infect Dis. 2019;69(4):726-31.  https://doi.org/10.1093/cid/ciz135  PMID: 30753348 
  9. Jiang HY, Shi YD, Zhang X, Pan LY, Xie YR, Jiang CM, et al. Human papillomavirus vaccination and the risk of autoimmune disorders: A systematic review and meta-analysis. Vaccine. 2019;37(23):3031-9.  https://doi.org/10.1016/j.vaccine.2019.04.049  PMID: 31036452 
  10. McGrogan A, Madle GC, Seaman HE, de Vries CS. The epidemiology of Guillain-Barré syndrome worldwide. A systematic literature review. Neuroepidemiology. 2009;32(2):150-63.  https://doi.org/10.1159/000184748  PMID: 19088488 
  11. Sejvar JJ, Baughman AL, Wise M, Morgan OW. Population incidence of Guillain-Barré syndrome: a systematic review and meta-analysis. Neuroepidemiology. 2011;36(2):123-33.  https://doi.org/10.1159/000324710  PMID: 21422765 
  12. Haber P, Sejvar J, Mikaeloff Y, DeStefano F. Vaccines and Guillain-Barré syndrome. Drug Saf. 2009;32(4):309-23.  https://doi.org/10.2165/00002018-200932040-00005  PMID: 19388722 
  13. Miranda S, Chaignot C, Collin C, Dray-Spira R, Weill A, Zureik M. Human papillomavirus vaccination and risk of autoimmune diseases: A large cohort study of over 2million young girls in France. Vaccine. 2017;35(36):4761-8.  https://doi.org/10.1016/j.vaccine.2017.06.030  PMID: 28750853 
  14. Boender TS, Harder T. Risk of Guillain-Barré Syndrome (GBS) after vaccination against human papillomavirus (HPV). PROSPERO No. #CRD42019123533. 2019. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019123533
  15. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6(7):e1000100.  https://doi.org/10.1371/journal.pmed.1000100  PMID: 19621070 
  16. Sejvar JJ, Kohl KS, Gidudu J, Amato A, Bakshi N, Baxter R, et al. Guillain-Barré syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2011;29(3):599-612.  https://doi.org/10.1016/j.vaccine.2010.06.003  PMID: 20600491 
  17. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.  https://doi.org/10.1136/bmj.l4898  PMID: 31462531 
  18. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919.  https://doi.org/10.1136/bmj.i4919  PMID: 27733354 
  19. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383-94.  https://doi.org/10.1016/j.jclinepi.2010.04.026  PMID: 21195583 
  20. Schünemann HJ, Cuello C, Akl EA, Mustafa RA, Meerpohl JJ, Thayer K, et al. GRADE guidelines: 18. How ROBINS-I and other tools to assess risk of bias in nonrandomized studies should be used to rate the certainty of a body of evidence. J Clin Epidemiol. 2019;111:105-14.  https://doi.org/10.1016/j.jclinepi.2018.01.012  PMID: 29432858 
  21. Farrington CP. Control without separate controls: evaluation of vaccine safety using case-only methods. Vaccine. 2004;22(15-16):2064-70.  https://doi.org/10.1016/j.vaccine.2004.01.017  PMID: 15121324 
  22. Brisson M, Van de Velde N, De Wals P, Boily M-C. Estimating the number needed to vaccinate to prevent diseases and death related to human papillomavirus infection. CMAJ. 2007;177(5):464-8.  https://doi.org/10.1503/cmaj.061709  PMID: 17709404 
  23. Cameron RL, Ahmed S, Pollock KGJ. Adverse event monitoring of the human papillomavirus vaccines in Scotland. Intern Med J. 2016;46(4):452-7.  https://doi.org/10.1111/imj.13005  PMID: 26765074 
  24. Lehtinen M, Eriksson T, Apter D, Hokkanen M, Natunen K, Paavonen J, et al. Safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in adolescents aged 12-15 years: Interim analysis of a large community-randomized controlled trial. Hum Vaccin Immunother. 2016;12(12):3177-85.  https://doi.org/10.1080/21645515.2016.1183847  PMID: 27841725 
  25. Bi D, Apter D, Eriksson T, Hokkanen M, Zima J, Damaso S, et al. Safety of the AS04-adjuvanted human papillomavirus (HPV)-16/18 vaccine in adolescents aged 12-15 years: end-of-study results from a community-randomized study up to 6.5 years. Hum Vaccin Immunother. 2020;16(6):1392-403.  https://doi.org/10.1080/21645515.2019.1692557  PMID: 31829767 
  26. Skufca J, Ollgren J, Artama M, Ruokokoski E, Nohynek H, Palmu AA. The association of adverse events with bivalent human papilloma virus vaccination: A nationwide register-based cohort study in Finland. Vaccine. 2018;36(39):5926-33.  https://doi.org/10.1016/j.vaccine.2018.06.074  PMID: 30115524 
  27. Grönlund O, Herweijer E, Sundström K, Arnheim-Dahlström L. Incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease after quadrivalent human papillomavirus vaccination: a cohort study. J Intern Med. 2016;280(6):618-26.  https://doi.org/10.1111/joim.12535  PMID: 27478093 
  28. Hviid A, Svanström H, Scheller NM, Grönlund O, Pasternak B, Arnheim-Dahlström L. Human papillomavirus vaccination of adult women and risk of autoimmune and neurological diseases. J Intern Med. 2018;283(2):154-65.  https://doi.org/10.1111/joim.12694  PMID: 29044769 
  29. Frisch M, Besson A, Clemmensen KKB, Valentiner-Branth P, Mølbak K, Hviid A. Quadrivalent human papillomavirus vaccination in boys and risk of autoimmune diseases, neurological diseases and venous thromboembolism. Int J Epidemiol. 2018;47(2):634-41.  https://doi.org/10.1093/ije/dyx273  PMID: 29425361 
  30. Grimaldi-Bensouda L, Guillemot D, Godeau B, Bénichou J, Lebrun-Frenay C, Papeix C, et al. Autoimmune disorders and quadrivalent human papillomavirus vaccination of young female subjects. J Intern Med. 2014;275(4):398-408.  https://doi.org/10.1111/joim.12155  PMID: 24206418 
  31. Grimaldi-Bensouda L, Rossignol M, Koné-Paut I, Krivitzky A, Lebrun-Frenay C, Clet J, et al. Risk of autoimmune diseases and human papilloma virus (HPV) vaccines: Six years of case-referent surveillance. J Autoimmun. 2017;79:84-90.  https://doi.org/10.1016/j.jaut.2017.01.005  PMID: 28190705 
  32. Andrews N, Stowe J, Miller E. No increased risk of Guillain-Barré syndrome after human papilloma virus vaccine: A self-controlled case-series study in England. Vaccine. 2017;35(13):1729-32.  https://doi.org/10.1016/j.vaccine.2017.01.076  PMID: 28245941 
  33. Willame C, Rosillon D, Zima J, Angelo MG, Stuurman AL, Vroling H, et al. Risk of new onset autoimmune disease in 9- to 25-year-old women exposed to human papillomavirus-16/18 AS04-adjuvanted vaccine in the United Kingdom. Hum Vaccin Immunother. 2016;12(11):2862-71.  https://doi.org/10.1080/21645515.2016.1199308  PMID: 27428517 
  34. Geier DA, Geier MR. A case-control study of quadrivalent human papillomavirus vaccine-associated autoimmune adverse events. Clin Rheumatol. 2015;34(7):1225-31.  https://doi.org/10.1007/s10067-014-2846-1  PMID: 25535199 
  35. Geier DA, Geier MR. Quadrivalent human papillomavirus vaccine and autoimmune adverse events: a case-control assessment of the vaccine adverse event reporting system (VAERS) database. Immunol Res. 2017;65(1):46-54.  https://doi.org/10.1007/s12026-016-8815-9  PMID: 27406735 
  36. Deceuninck G, Sauvageau C, Gilca V, Boulianne N, De Serres G. Absence of association between Guillain-Barré syndrome hospitalizations and HPV-vaccine. Expert Rev Vaccines. 2018;17(1):99-102.  https://doi.org/10.1080/14760584.2018.1388168  PMID: 28972438 
  37. Chao C, Klein NP, Velicer CM, Sy LS, Slezak JM, Takhar H, et al. Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. J Intern Med. 2012;271(2):193-203.  https://doi.org/10.1111/j.1365-2796.2011.02467.x  PMID: 21973261 
  38. Gee J, Naleway A, Shui I, Baggs J, Yin R, Li R, et al. Monitoring the safety of quadrivalent human papillomavirus vaccine: findings from the Vaccine Safety Datalink. Vaccine. 2011;29(46):8279-84.  https://doi.org/10.1016/j.vaccine.2011.08.106  PMID: 21907257 
  39. Gee J, Sukumaran L, Weintraub E. Risk of Guillain-Barré Syndrome following quadrivalent human papillomavirus vaccine in the Vaccine Safety Datalink. Vaccine. 2017;35(43):5756-8.  https://doi.org/10.1016/j.vaccine.2017.09.009  PMID: 28935469 
  40. Donahue JG, Kieke BA, Lewis EM, Weintraub ES, Hanson KE, McClure DL, et al. Near real-time surveillance to assess the safety of the 9-valent Human Papillomavirus Vaccine. Pediatrics. 2019;144(6):e20191808.  https://doi.org/10.1542/peds.2019-1808  PMID: 31740498 
  41. Slade BA, Leidel L, Vellozzi C, Woo EJ, Hua W, Sutherland A, et al. Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. JAMA. 2009;302(7):750-7.  https://doi.org/10.1001/jama.2009.1201  PMID: 19690307 
  42. Souayah N, Michas-Martin PA, Nasar A, Krivitskaya N, Yacoub HA, Khan H, et al. Guillain-Barré syndrome after Gardasil vaccination: data from Vaccine Adverse Event Reporting System 2006-2009. Vaccine. 2011;29(5):886-9.  https://doi.org/10.1016/j.vaccine.2010.09.020  PMID: 20869467 
  43. Ojha RP, Jackson BE, Tota JE, Offutt-Powell TN, Singh KP, Bae S. Guillain-Barre syndrome following quadrivalent human papillomavirus vaccination among vaccine-eligible individuals in the United States. Hum Vaccin Immunother. 2014;10(1):232-7.  https://doi.org/10.4161/hv.26292  PMID: 24013368 
  44. Arana JE, Harrington T, Cano M, Lewis P, Mba-Jonas A, Rongxia L, et al. Post-licensure safety monitoring of quadrivalent human papillomavirus vaccine in the Vaccine Adverse Event Reporting System (VAERS), 2009-2015. Vaccine. 2018;36(13):1781-8.  https://doi.org/10.1016/j.vaccine.2018.02.034  PMID: 29477308 
  45. Neha R, Subeesh V, Beulah E, Gouri N, Maheswari E. Postlicensure surveillance of human papillomavirus vaccine using the Vaccine Adverse Event Reporting System, 2006-2017. Perspect Clin Res. 2020;11(1):24-30.  https://doi.org/10.4103/picr.PICR_140_18  PMID: 32154146 
  46. Verstraeten T, Descamps D, David MP, Zahaf T, Hardt K, Izurieta P, et al. Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines. Vaccine. 2008;26(51):6630-8.  https://doi.org/10.1016/j.vaccine.2008.09.049  PMID: 18845199 
  47. Shimabukuro TT, Nguyen M, Martin D, DeStefano F. Safety monitoring in the vaccine adverse event reporting system (VAERS). Vaccine. 2015;33(36):4398-405.  https://doi.org/10.1016/j.vaccine.2015.07.035  PMID: 26209838 
  48. Baggs J, Gee J, Lewis E, Fowler G, Benson P, Lieu T, et al. The Vaccine Safety Datalink: a model for monitoring immunization safety. Pediatrics. 2011;127(Suppl 1):S45-53.  https://doi.org/10.1542/peds.2010-1722H  PMID: 21502240 
  49. Mouchet J, Salvo F, Raschi E, Poluzzi E, Antonazzo IC, De Ponti F, et al. Human papillomavirus vaccine and demyelinating diseases-A systematic review and meta-analysis. Pharmacol Res. 2018;132:108-18.  https://doi.org/10.1016/j.phrs.2018.04.007  PMID: 29665426 
  50. Meggiolaro A, Migliara G, La Torre G. Association between Human Papilloma Virus (HPV) vaccination and risk of Multiple Sclerosis: A systematic review. Hum Vaccin Immunother. 2018;14(5):1266-74.  https://doi.org/10.1080/21645515.2017.1423155  PMID: 29333935 
  51. Genovese C, LA Fauci V, Squeri A, Trimarchi G, Squeri R. HPV vaccine and autoimmune diseases: systematic review and meta-analysis of the literature. J Prev Med Hyg. 2018;59(3):E194-9. PMID: 30397675 
  52. Koch JHT, von Kries R, Wichmann O. The risk of intussusception after rotavirus vaccination—a systematic literature review and meta-analysis. Dtsch Arztebl. 2017;114(15):255-62.
  53. Ammon A, Prats Monné X. Vaccines, trust and European public health. Euro Surveill. 2018;23(17).  https://doi.org/10.2807/1560-7917.ES.2018.23.17.18-00210  PMID: 29717694 
  54. European Centre for Disease Prevention and Control (ECDC). Let’s talk about hesitancy. Stockholm: ECDC; 2016. Available from: https://www.ecdc.europa.eu/sites/default/files/media/en/publications/Publications/lets-talk-about-hesitancy-vaccination-guide.pdf
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