A recent case report about a death of a 15-year-old boy from a form of acute disseminated encephalomyelitis (ADEM) after receiving the quadrivalent HPV vaccine has been widely shared by anti-vaccine groups. Of course, I wanted to look into any potential link between ADEM and the HPV vaccine.
Before I start looking at the evidence, I must point out that case reports have little meaning in the hierarchy of vaccine research. To be honest, case reports, even if they’re published in high-quality journals, barely rise above anecdotes as evidence. Why? They are nothing more than a report without being able to establish causality. But most importantly, they represent an n=1 research population, which tells us little. And it doesn’t show correlation, let alone causation.
We’ve also discussed ADEM before – the tragic story of Christopher Bunch whose mother blamed the HPV vaccine for causing his ADEM.
Setting that aside, is there any evidence that shows any link (or lack of a link) between acute disseminated encephalomyelitis and the HPV vaccine? Let’s take a look at this evidence.
What is acute disseminated encephalomyelitis
Acute disseminated encephalomyelitis is an autoimmune disease that is characterized by a brief but widespread attack of inflammation in the brain and spinal cord that damages myelin – the protective covering of nerve fibers. ADEM often follows viral or bacterial infections, or less often, vaccination for measles, mumps, or rubella.
Treatment for ADEM is targeted at suppressing inflammation in the brain using anti-inflammatory drugs. Most individuals respond to several days of intravenous corticosteroids such as methylprednisolone, followed by oral corticosteroid treatment.
The short-and long-term prognosis for individuals with ADEM is favorable with proper diagnosis and treatment.
HPV vaccines and ADEM
There is no evidence supporting a link between HPV vaccines and ADEM. According to Vaxopedia,
Acute disseminated encephalomyelitis (ADEM) is characterized by a brief but widespread attack of inflammation in the brain and spinal cord that damages myelin – the protective covering of nerve fibers. ADEM often follows viral or bacterial infections, or less often, vaccination for measles, mumps, or rubella.
ADEM is a serious, life-threatening condition, though it can be treated. It is usually preceded by a viral or bacterial infection. Rarely, it can happen after a vaccine. The incidence of ADEM is so rare that it is difficult to conclusively establish a link between any vaccine and ADEM. This is further complicated by the fact that 30% of ADEM cases do not have a known trigger.
So we have a very serious, potentially fatal event, that can, in rare instances, happen after vaccines, though is much more likely after infections, including infections that vaccines prevent (in other words, you’re less likely to get ADEM if you vaccinate).
Of course, unless we want to employ the post hoc fallacy, we know that just because something happens after a vaccine, it does not mean it was caused by the vaccine. The question is, do vaccines cause ADEM? A recent study examined this in a database with 64 million vaccine doses. It found a slight increase (excess risk of 1.16 cases of ADEM per million vaccine doses) in the risk of ADEM in the 5-28 days following Tdap vaccines. But not for other vaccines, including HPV.
Other large studies that looked at HPV vaccines and demyelinating diseases also did not find such a link (here, here, and here). A review of 2 million doses of the HPV vaccine showed no increased risk for acute disseminated encephalomyelitis.
Inevitably, when you vaccinate large numbers of people, you will have some bad things happen after the vaccines. Hundreds of millions of doses of HPV vaccines have been given worldwide. And some individual cases of ADEM were reported after HPV vaccines (in both these studies, after the second dose).
These cases can raise the question of whether there is a link; but single observations cannot show a link, because some such cases are bound to happen by coincidence alone. The large studies cited above examine whether these individual reports are a coincidence or show a causal connection, and they suggest that these reports are coincidental.
Biological plausibility
Is there a biologically plausible mechanism that could link the HPV vaccine and ADEM?
The etiology of acute disseminated encephalomyelitis is not well understood. However, Biological mechanisms proposed to explain the immunogenic etiology of ADEM following infection or immunization include direct destruction and molecular mimicry, which refers to the possibility that similar epitopes shared between self-peptides and foreign peptides (introduced via infection or immunization) inadvertently cause the activation of autoreactive T or B cells, leading to autoimmunity against the myelin.
Although these are potential mechanisms that are biologically plausible, no evidence has been presented that these in fact exist between the antigens in the HPV vaccine and the myelin.
Summary
In summary, extensive evidence – and the lack of evidence of a plausible biological mechanism – go against a link between HPV vaccines and autoimmune conditions such as acute disseminated encephalomyelitis.
Case studies that try to blame HPV vaccines are interesting to determine if there is a potential link, but they rarely give any data for confounders that may help us better understand if there is an actual link. Like with the sad case of Christopher Bunch, we find out that he suffered from an infection that probably was the causal factor for his ADEM and the HPV vaccination was just coincidental.
I know that most readers here know how to discern high-quality scientific research from moderate- or low-quality research. Case reports, even ones that seem very serious, don’t rise to the top of the hierarchy of medical research. They just can’t tell us anything about a link between acute disseminated encephalomyelitis and the HPV vaccine.
But we do have large, well-designed studies that haven’t found a link. Those do rise to the top of the hierarchy of evidence.
Right now, given the preponderance of the evidence, there appears to be no link between the HPV vaccine and ADEM.
Citations
- Grimaldi-Bensouda L, Guillemot D, Godeau B, Bénichou J, Lebrun-Frenay C, Papeix C, Labauge P, Berquin P, Penfornis A, Benhamou PY, Nicolino M, Simon A, Viallard JF, Costedoat-Chalumeau N, Courcoux MF, Pondarré C, Hilliquin P, Chatelus E, Foltz V, Guillaume S, Rossignol M, Abenhaim L; PGRx-AID Study Group. Autoimmune disorders and quadrivalent human papillomavirus vaccination of young female subjects. J Intern Med. 2014 Apr;275(4):398-408. doi: 10.1111/joim.12155. Epub 2013 Nov 22. PMID: 24206418.
- Harter DH, Choppin PW. Possible mechanisms in the pathogenesis of “postinfectious” encephalomyelitis. Res Publ Assoc Res Nerv Ment Dis. 1971;49:342-55. PMID: 4332337.
- Miller SD, McRae BL, Vanderlugt CL, Nikcevich KM, Pope JG, Pope L, Karpus WJ. Evolution of the T-cell repertoire during the course of experimental immune-mediated demyelinating diseases. Immunol Rev. 1995 Apr;144:225-44. doi: 10.1111/j.1600-065x.1995.tb00071.x. PMID: 7590815.
- Phillips A, Patel C, Pillsbury A, Brotherton J, Macartney K. Safety of Human Papillomavirus Vaccines: An Updated Review. Drug Saf. 2018 Apr;41(4):329-346. doi: 10.1007/s40264-017-0625-z. PMID: 29280070.
- Scheller NM, Svanström H, Pasternak B, Arnheim-Dahlström L, Sundström K, Fink K, Hviid A. Quadrivalent HPV vaccination and risk of multiple sclerosis and other demyelinating diseases of the central nervous system. JAMA. 2015 Jan 6;313(1):54-61. doi: 10.1001/jama.2014.16946. PubMed PMID: 25562266.
- Sekiguchi K, Yasui N, Kowa H, Kanda F, Toda T. Two Cases of Acute Disseminated Encephalomyelitis Following Vaccination Against Human Papilloma Virus. Intern Med. 2016;55(21):3181-3184. doi: 10.2169/internalmedicine.55.5472. Epub 2016 Nov 1. PMID: 27803416; PMCID: PMC5140871.
- Wellnitz K, Sato Y, Bonthius DJ. Fatal Acute Hemorrhagic Leukoencephalitis Following Immunization Against Human Papillomavirus in a 14-Year-Old Boy. Child Neurol Open. 2021 May 18;8:2329048X211016109. doi: 10.1177/2329048X211016109. PMID: 34046515; PMCID: PMC8135193.
- Wildemann B, Jarius S, Hartmann M, Regula JU, Hametner C. Acute disseminated encephalomyelitis following vaccination against human papilloma virus. Neurology. 2009 Jun 16;72(24):2132-3. doi: 10.1212/WNL.0b013e3181aa53bb. PMID: 19528522.
