HPV vaccine autoimmunity – more bad science from Shoenfeld

We just posted an article by Professor Dorit Rubinstein Reiss who criticized many of Dr. Yehuda Shoenfeld‘s anti-vaccine ideas, which include HPV vaccine autoimmunity. We need to examine and critique a new paper from Shoenfeld which tries to establish why the HPV vaccine might cause autoimmunity. Spoiler alert – it’s not very good.

For some reason, Shoenfeld has targeted the HPV cancer-prevention vaccine in much of his “research” lately. He has taken that niche and run with it. And, because the anti-vaxxers love their argument from false authority, Shoenfeld is a hero to them.

So is there any validity to the HPV vaccine autoimmunity claim? Not really, but let’s take a scientific critique of it.

HPV vaccine autoimmunity

Does HPV vaccine autoimmunity exist?

Before we get into the HPV vaccine autoimmunity article, let’s just look at it from the 10,000-meter height. Shoenfeld employs one of the basic tenets of pseudoscience – he invented a discredited conclusion, then he does all that he can do to support his narrative.

Real science accumulates all evidence through the scientific method and only then, a good scientist sees where the evidence leads. 

Shoenfeld invented something called ASIA – autoimmune syndrome induced by adjuvants – as a risk for receiving the cancer-preventing HPV vaccine. However, there is simply no evidence that ASIA exists.

It is not accepted by the scientific and medical community (and see this published article), was rejected by the United States vaccine court as a claim for vaccine injury, and should not be accepted by parents deciding whether they should vaccinate their children.

Furthermore, the European Medicines Agency, which is the primary regulatory body in the EU for pharmaceuticals, has rejected any link between the HPV vaccine and various autoimmune disorders. The science stands in direct opposition to autoimmune syndromes being caused by any vaccine.

Moreover, the respected World Health Organization (WHO)  has scientifically rejected the quackery of ASIA (if it even exists) is caused by vaccines, notably, the HPV vaccine.

A while ago, I reviewed another study, which was a properly designed case-control epidemiological study. According to the study published in the Journal of Autoimmunity, HPV vaccines do not increase the risk of developing autoimmune diseases (ADs). This adds to the body of research, based on a methodology that helps us establish correlation and causation, that rejects the hypothesis that the HPV vaccine is related to ASIA.

In this study, the authors evaluated the risk of autoimmune diseases over 6.5 year period after exposure to HPV vaccines (quadrivalent Gardasil and bivalent Cervarix) in adolescent and young adult women using data from a French medical registry, Pharmacoepidemiologic General Research eXtension (PGRx). The PGRx is a surveillance database that helps researchers monitor the occurrence of rare or delayed health events that may be related to the use of medications, including vaccines.

Here are the published results of the study:

  • A total of 478 cases with AD against 1869 matched controls with no AD were included in the case-control study. A large majority of individuals in both the AD and control groups had received the quadrivalent Gardasil vaccine (95.3%). Additionally, over half of the study population had been exposed to at least one other vaccine during the 24 months before inclusion in the study
  • The HPV vaccine uptake rate was lower in the patients with AD than in the controls without AD (10.9% vs 22.5%).
  • Surprisingly, the group receiving an HPV vaccine had a more than 40% lower observed risk of developing AD. A similar lowered risk of central demyelination/multiple sclerosis (CD/MS) and autoimmune thyroiditis (AT) was observed in the HPV vaccine group. The researchers observed a statistically nonsignificant trend for reduced risk of connective tissue disease (CTD) and type 1 diabetes (T1D) after vaccination.
  • No correlation was found between HPV vaccine exposure and idiopathic thrombocytopenic purpura (ITP). The relationship between HPV vaccine exposure and Guillain-Barré syndrome (GBS) could not be established since no cases of GBS occurred in individuals who received an HPV vaccine.

The authors concluded:

Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.

There are several other studies that have also shown no link between the HPV vaccine and autoimmune diseases:

  • David Hawkes et al. concluded that “At present, there is no evidence to suggest that ASIA syndrome is a viable explanation for unusual autoimmune diseases. The current studies involving human cases are so diverse, in both external stimuli and in resulting conditions, that there is currently a lack of reproducible evidence for any consistent relationship between adjuvant and autoimmune condition.” Though Dr. Hawkes utilizes the typical scientific verbiage along the lines of “we need to study it more,” at present, there is simply no evidence supporting the existence of ASIA.
  • Kristine Macartney et al. stated that “We identified 109 studies, including 15 population-based studies in over 2.5 million vaccinated individuals across six countries. All vaccines demonstrated an acceptable safety profile; injection-site reactions were slightly more common for 9vHPV vaccine than for 4vHPV vaccine. There was no consistent evidence of an increased risk of any AESI (adverse event of special interest), including demyelinating syndromes or neurological conditions such as complex regional pain or postural orthostatic tachycardia syndromes.”
  • Lamiae Grimaldi-Bensouda et al. concluded that “Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.”
  • Rohan Ameratunga et al. agreed that “Current data do not support the causation of ASIA by vaccine adjuvants containing aluminum, which should be of reassurance to patients undergoing routine immunizations.”

These are all large population groups of study subjects, and the common conclusions are that ASIA, or any autoimmune disease, is not linked to vaccines, including the HPV vaccine. We just don’t have any evidence that HPV vaccine autoimmunity exists, yet Shoenfeld keeps trying to find the monster in the closet.

So let’s take a look at his new study.

ASIA, once again by Yehuda Shoenfeld

Shoenfeld’s new article, published in an obscure, low impact-factor journal, Pathobiology, attempted to show that there is a biologically plausible mechanism to show that the antigens in the HPV vaccine are exactly similar to peptides in various cells of the human. Thus, antibodies would cross-react between the HPV antigens and human cells, causing numerous autoimmune conditions, or ASIA.

Of course, we have laid out the vast body of evidence that no one has ever found ASIA (even if it exists, there’s nothing that suggests that it’s related to vaccines). Obviously, Shoenfeld believes it exists, so he’s going to do anything he can to establish some mechanism as to why it does.

Shoenfeld concludes that:

Immunologically, the high extent of peptide sharing between the HPV L1 epitopes and human proteins invites to revise the concept of the negative selection of self-reactive lymphocytes. Pathologically, the data highlight a cross-reactive potential for a spectrum of autoimmune diseases that includes ovarian failure, systemic lupus erythematosus (SLE), breast cancer and sudden death, among others. Therapeutically, analyzing already validated immunoreactive epitopes filters out the peptide sharing possibly exempt of self-reactivity, defines the effective potential for pathologic autoimmunity, and allows singling out peptide epitopes for safe immunotherapeutic protocols.

Setting aside the fact that breast cancer risk seems to be inversely related to autoimmune diseases (in other words, there isn’t much evidence that breast cancer is an autoimmune disease), or that ovarian failure and sudden death (SIDS) are related to vaccines, let’s do our typical skepticism toward this “research” regarding HPV vaccine autoimmunity.

  1. Shoenfeld ignores that there are many viral antigens that share components with components within systems. Almost all of these do not cause autoimmune diseases – in other words, sharing “epitopes” is not relevant to autoimmune disease by itself.
  2. Some of the human proteins examined by Shoenfeld never leave the cell – they would never be attacked by antibodies (and never lead to some sort of autoimmune cross-reactivity).
  3. They did not establish that these cross-reactive epitopes between humans and the HPV antigen actually induce an immune response that would lead to an autoimmune disease. This is amusing, since they are trying to establish a biological mechanism, and they don’t.
  4. They claim that a natural HPV infection doesn’t induce this molecular mimicry despite the fact that the HPV vaccine, in order to induce an immune response, contains the same antigens as a “natural” HPV virus. I’m getting a headache thinking about the pretzel logic here.
  5. Shoenfeld claims that “Clinically, such a vast cross-reactivity potential explains the multiple autoimmune disease syndromes that can follow infections/active immunization.” They then cite an article, to support this wild claim, which actually has nothing to do with vaccines or immunization. It’s a case study of one patient with thymoma, a cancer of the thymus gland. Wait, my head needs to hit the desk.
  6. Dr. David Hawkes wrote, in a private discussion about this article, “I’ve looked at the first 30 amino acids of the HPV16 L1 protein and there are 26 different five amino acid sequences! If you have a gene that produces a protein of 500 amino acids (that’s not a large protein) then I imagine there would be a five amino acid sequence in common with at least one of the nine HPV type L1 sequences in the Gardasil9 vaccine. Remember that HPV types are defined as being more than 10% different DNA sequence than any other HPV type L1 sequence.” In other words, Shoenfeld tried to “prove” that these five amino acid sequences would cross-react with random proteins in human cells – but these sequences are so common that it’s difficult to conclude that there would actually be cross-reactivity. Based on this false narrative, any virus would cause a human to collapse into a puddle of autoimmune disease. We don’t observe this phenomenon.

This article shows us nothing with regard to the possibly nonexistent ASIA and the HPV vaccine. Nothing. Of course, it is settled science that vaccines are not related to ASIA, irrespective of the fact that it may not even exist.

The only reason that you’d look hard for a biological mechanism like this is in an attempt to show that it is reasonable to believe that the correlation between vaccines and ASIA can establish causation. The problem with this pseudoscience is that we have not only not established correlation, but we have also clearly rejected its existence period.

Science!

Summary

This is an unbelievable study that shows us nothing. We haven’t seen any legitimate, robust published evidence that there is anything to HPV vaccine autoimmunity like ASIA. Nothing. 

In fact, we do not have any legitimate, robust published evidence that ASIA, even if it does exist, is related to any vaccine, let alone the HPV vaccine. This is settled science, and the only way to “unsettle” it is to give us the evidence.

Dr. Shoenfeld was once a good scientist – unfortunately, he has gone off the rails with this HPV vaccine autoimmunity narrative. He has yet to give us any substantiation that either ASIA exists or that there is some relationship between vaccines and autoimmunity. 

This should be his first step – lead a large epidemiological or clinical study that provides convincing evidence of ASIA. Then, show us some biologically plausible mechanism (and this study isn’t it, it’s truly awful).

Notes

Much of the critique comes from a set of private conversations about the article. Those who contributed to this discussion know who you are! And many thanks for helping out (intentionally or not).

Citations



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The Original Skeptical Raptor
Chief Executive Officer at SkepticalRaptor
Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!

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