HPV vaccine anecdotes – not the basis of real science

Anecdotes are a fundamental part of the anti-vaccine propaganda machine. We have a tendency to overstate the importance of anecdotes, because they usually have an emotional appeal to them. Anecdotes are not data, not even close. At best, they are observations, but they give no indication of temporal correlation, let alone causality.

HPV vaccine anecdotes have become part of the discourse about Gardasil and other HPV vaccines. It has become  full-time job just to debunk the myths that arise from a handful of anecdotes.

I have written on a number of articles about the HPV cancer-prevention vaccines, Gardasil, Cervarix and Silgard. These vaccines prevent infection by up to 9 different types of genital and oral human papillomavirus (HPV), the most common sexually transmitted infection (STI) in the USA.

The virus is generally transmitted from personal contact during vaginal, anal or oral sex. It is very easy to transmit, and according to the CDC, roughly 79 million Americans are infected with HPV–approximately 14 million Americans contract HPV every year.

HPV is believed to cause nearly 5% of all new cancers across the world, making it almost as dangerous with regards to cancer as tobacco. Most individuals don’t even know they have the infection until the onset of cancer. And about 27,000 HPV-related cancers are diagnosed in the USA every year.

There is  a robust body of evidence supporting the fact that HPV vaccines are highly effective in preventing HPV infection. There are also several large studies (also, here and here) that strongly support the high degree of safety of the HPV vaccine.

Recently, the European Medicines Agency (EMA, European Union’s version of the US FDA) had started a review of human papilloma virus (HPV) vaccines “to further clarify aspects of their safety profile,” although the agency also points out that this review “does not question that the benefits of HPV vaccines outweigh their risks.”

The outcome? The EMA found that the HPV vaccine was safe.

Science vs HPV vaccine anecdotes

 

This EMA review was initiated at the request of Denmark (countries can make requests of European regulatory agencies to undergo reviews of drugs). This review examined data for two conditions that have been reported, rarely, with HPV vaccines:

  • postural orthostatic tachycardia syndrome (POTS), a difficult-to-diagnose condition in which a change from the supine position  to an upright position causes an abnormally large increase in heart rate, called tachycardia. This can cause symptoms such as dizziness and fainting, as well as headache, chest pain, and weakness.
  • complex regional pain syndrome (CRPS), a chronic pain condition affecting the limbs. CRPS can sometimes overlap with, or be conflated with, chronic fatigue syndrome (CFS).

As any good regulatory agency would do, EMA noticed a lot of anecdotes and observations, and looked to see if there was any conclusive evidence that would support correlation and causation between the vaccine and POTS, CRPS, or CFS.

The EMA stated that “both conditions can occur in non-vaccinated individuals and it is considered important to further review if the number of cases reported with HPV vaccine is greater than would be expected.”

 
 

Of course, as I mentioned above, the EMA found no causal link between these conditions and HPV vaccines have been established.

But that never stops the vaccine deniers, because if they think something exists, they look for evidence to support their beliefs, the method of pseudoscience rather than real science.

We’ve seen this before with vaccines. Mr. Andy Wakefield, the cunning fraud, invented a link between vaccines and autism, causing a drop in measles vaccination rates. So, billions of dollars had to be wasted to show, over and over, that vaccines are unrelated to autism.

Today, we have people bringing unscientific anecdotes to the discussion about HPV cancer prevention vaccines, and convincing national governments, like Denmark, to waste millions of dollars in looking at these issues again and again.

[nextpage title=”Next page”]

HPV vaccine and POTS

 

I guess we should first start out with what is POTS itself. Officially, it’s called postural orthostatic tachycardia syndrome, a condition in which a change from the supine position to an upright position causes an abnormally large increase in heart rate, called tachycardia.

POTS is generally diagnosed when a patient’s heart rate increases suddenly when they stand up or sit up from a lying down position, although there has to be other information to form a definitive diagnosis.

POTS is relatively common in young women. It is estimated that there are around 500,000 to 3,000,000 cases per year in the USA, an incidence rate of roughly 1 out of 100 individuals. It could be far higher because it is difficult to diagnose.

The suspicion that POTS might be related the HPV vaccine can be tied to a study published earlier in 2015. The study, by Danish researchers, provided some observational evidence about POTS occurrence after HPV vaccines.

The authors of the study reported that:

[infobox icon=”quote-left”]All patients had symptoms consistent with pronounced autonomic dysfunction including different degrees of orthostatic intolerance, severe non-migraine-like headache, excessive fatigue, cognitive dysfunction, gastrointestinal discomfort and widespread pain of a neuropathic character.[/infobox]

The authors also stated that they “found a close chronologic association to the vaccination, but are well aware that this does not necessarily imply a causal relationship (emphasis mine).”

 
 

I heavily critiqued this study, focusing on several points:

  • It’s a case report study. In other words, it’s observations that cannot provide us with an answer to the hypothesis, “does the HPV vaccine cause POTS.” Case reports show up in the medical literature all of the time, but the vast majority don’t amount to real evidence for clinical decisions.
  • There are no controls.
  • Small sample size. There were only 35 patients included in the study.
  • Confounding variables. In the small patient population of this, there were variables that were not fully explained, like heavy exercise by most of the patients prior to the study, that may have more importance than vaccination status.
  • Poor temporal association. The study found that the average number of days between vaccination and diagnosing POTS was around 11 days. It is difficult to conceive of how one could even claim an association without a thorough investigation of the confounding factors that may have occurred in the ensuing 11 days that might have lead to POTS.
  • No biological plausibility. To even begin to make a claim of correlation or causation, one has to provide some level of plausibility. It is difficult to make a plausible explanation how the HPV antigens could possibly cause POTS, unless we start with some plausible hypothesis that HPV itself causes POTS.
  • POTS is common in teenage and young adult females. It’s possible that far about 1 out every 100 young women might have POTS, irrespective of HPV vaccination status.
  • Diagnosing POTS. Diagnosing this condition is not easy (pdf). It isn’t done in a minute–a definitive diagnosis requires blood tests, including tests for hormonal deficiencies, a specialized tilt table test under controlled conditions, and a few other tests to get a definitive diagnosis. These researchers diagnosed POTS with one test–heart rate, which can be indicative of many other, and unrelated, medical conditions.
  • The authors’ bias. I usually don’t care about the authors, unless they are really bad or really good. These authors seem to have a history of bias against the HPV vaccine.

Possibly because the researchers are Danish, and possibly because the Danish Health ministry wants to demolish this belief as quickly as possible, but they are funding research to examine whether these HPV vaccine anecdotes, at least as related to POTS, have any basis in science.

[nextpage title=”Next page”]

HPV vaccine and CRPS

 

Complex regional pain syndrome, like POTS, is a difficult to diagnose illness. Moreover, POTS and CRPS have overlapping symptoms and other clinical features that make them difficult to separate from one another.

CRPS is a chronic systemic disease characterized by severe pain, swelling, and changes in the skin. It is generally caused by a minor or severe injury to nerves. There has never been evidence that CRPS is related to any vaccine, let alone the HPV cancer preventing vaccine.

In June 2015, Dr. Manuel Martínez-Lavín proposed a hypothesis that small fiber neuropathy and dysautonomia could be the common underlying pathogenesis for this group of rare, but severe, reactions that follow HPV vaccination. In other words, by some unknown pathway, the HPV vaccine could cause CRPS.

But this study isn’t based on clinical trials–it is the author’s opinion and conjecture in what can best be described as a low quality journal (with an impact factor less than 1.7).

Dr. Martínez-Lavín, who is from the Rheumatology Department, Instituto Nacional de Cardiología Ignacio Chávez in Mexico City, Mexico, claims that:

[infobox icon=”quote-left”]”The symptoms more often reported are chronic pain with paresthesias, headaches, fatigue, and orthostatic intolerance. Adverse reactions appear to be more frequent after HPV vaccination when compared to other type[s] of immunizations. Different isolated cases and small series have described the development of [CRPS], [POTS], and fibromyalgia after HPV vaccination.”[/infobox]

Basically, Dr Martínez-Lavín proposes a hypothesis that small fiber neuropathy and dysautonomia could be the common underlying pathogenesis for this group of rare, but severe, reactions that follow HPV vaccinations. He wants to make clinicians aware of a “possible association” between the HPV vaccine and the development of these syndromes.

Most importantly, Dr. Martínez-Lavín partially bases his hypothesis on the aforementioned POTS and HPV vaccine study that has been heavily criticized. So one poorly designed, potentially biased study, leads to another huge hypothesis? I’m finding it difficult to see the link.

So, Dr. Martínez-Lavín takes a condition that probably isn’t related to the HPV vaccine, and tries to support it with a “plausible hypothesis.” Sure, we should demand plausibility in making a case for a causal relationship between the HPV vaccine and POTS or CRPS, but he didn’t actually show plausibility. It’s a circular argument that gives me a serious headache.

[nextpage title=”Next page”]

Why is Denmark looking at this again?

 

Let me remind the readers that the EMA spent several months evaluating any links between the HPV vaccines and POTS, CRPS and CFS. Here’s what they concluded:

[infobox icon=”quote-left”]The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) has completed a detailed scientific review of the evidence surrounding reports of two syndromes, complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS) in young women given human papillomavirus (HPV) vaccines. These vaccines are given to protect them from cervical cancer and other HPV-related cancers and pre-cancerous conditions.

 
 

This review concluded that the evidence does not support a causal link between the vaccines (Cervarix, Gardasil/Silgard and Gardasil-9) and development of CRPS or POTS. Therefore, there is no reason to change the way the vaccines are used or amend the current product information.

Symptoms of CRPS and POTS may overlap with other conditions, making diagnosis difficult in both the general population and vaccinated individuals. However, available estimates suggest that in the general population around 150 girls and young women per million aged 10 to 19 years may develop CRPS each year, and at least 150 girls and young women per million may develop POTS each year.

The review found no evidence that the overall rates of these syndromes in vaccinated girls were different from expected rates in these age groups, even taking into account possible underreporting. The PRAC noted that some symptoms of CRPS and POTS may overlap with chronic fatigue syndrome (CFS, also known as myalgic encephalomyelitis or ME). Many of the reports considered in the review have features of CFS and some patients had diagnoses of both POTS and CFS. Results of a large published study that showed no link between HPV vaccine and CFS were therefore particularly relevant.

The PRAC concluded that the available evidence does not support that CRPS and POTS are caused by HPV vaccines. Therefore there is no reason to change the way the vaccines are used or amend the current product information (emphasis mine).[/infobox]

In other words, they looked at boatloads of published and unpublished data, and they found nothing.

But that doesn’t stop the story, it never does. Using the Argument from Ignorance logical fallacy, we apparently have not asked the right question(s).

According to the highly biased article in Medscape, there are apparently lots of reasons to dismiss the EMA report:

  • Jesper Mehlsen, MD, director of research at the Coordinating Research Centre/Syncope Unit at Frederiksberg Hospital, Denmark, was the lead author in study of young women and girls with symptoms that began less than 2 months after vaccination. According to Dr. Mehlsen, “se suspect a connection to the HPV vaccine due to the close temporal association and the lack of alternative explanations.” Well, I beg to differ.
  • Dr Mehlsen also said: “Unfortunately the decision is based on register studies with a focus on POTS and CRPS. These diagnostic entities are only part of the symptom complex, which bear a closer relationship to chronic fatigue syndrome. In some countries, POTS is not registered as a diagnosis and patients are classified under different diagnoses in different countries. Finally, a lot of the reporting stems from the producers of the vaccines, allowing for possible heavy bias in the data.” First, move the goalposts, by claiming that their POTS diagnosis is somehow superior to others. And second, if all else fails, blame Big Pharma.
  • The Medscape article then quoted another poorly done study, which included just six cases. Yes, six. The author, Svetlana Blitshteyn, MD, clinical assistant professor of neurology at the University at Buffalo School of Medicine in New York, claims that these patients were diagnosed with POTS, small fiber neuropathy, fibromyalgia, chronic daily headache, and other disorders that began shortly after HPV vaccination. Blitshteyn then claimed that, “most of these young women were healthy prior to vaccination, and many were competitive athletes. After developing postvaccination syndrome, these patients became very ill, experienced significant decline in functioning, and were unable to attend school, participate in their previous athletic activities, or maintain their grades.” Great selection bias there, since the patients came to see a neurologist because they had neurological dysfunction. Her study shows nothing. (See Note 1).

I could go on and on and on about this Medscape hit piece. It mentioned online videos in Japan that show no link between the HPV vaccine and anything, but are very emotional. Or relying upon a questionnaire (how do you even eliminate any confirmation or observation bias by sending out a questionnaire) as “evidence” for a link.

Of course, the author of that article ignores a study of 1.6 million (yes, million) doses administered, which saw no POTS or CRPS (or actually anything).

And there was another study, that included over 1 million (once again, yes, million) patients, ironically in Denmark and Sweden, found nothing.

Or the study of 200,000 patients, where their medical records were tracked for six months, that again, showed no link between the HPV vaccine and POTS.

The US FDA and CDC have reported, after nearly 80 million doses of HPV vaccine delivered since 2006, no causal association between the vaccine and neuropathic pain and autonomic dysfunction. In other words, with that many doses, why aren’t we observing an epidemic of POTS, CRPS and CFS in the USA above the 1 out of 100 incidence that’s been observed before the vaccine was launched.

With these detailed studies and large population observations, most based on well-kept medical records in several countries, researchers just haven’t seen a link between the vaccine and these disorders. As opposed to the assertion made by the Medscape article, researchers do not have to “power” the study to look for POTS or CRPS. That actually forces unintentional bias into the study. After millions of doses, we’d see a pattern.

[nextpage title=”Next page”]

Summary

 

First of all, the Medscape article, written by Zoysia Chustecka, should be criticized heavily for false balance, something that’s used by those in the press who push the manufactroversy with regards to vaccines and autism. Chustecka did not even try to present balance to this article, quoting anti-vaccine researchers for the first three and a half pages. It wasn’t until the last couple of paragraphs did Chustecka even mention the massive amount of evidence that refuted any link.

It’s up to Denmark to do whatever it wants with this research. The USA and Europe spent boatloads of money refuting the zombie myth that vaccines cause autism. And even then, many deny the evidence.

I know some people ascribe to the precautionary principle, and we should examine observational evidence carefully. I agree to a point–if the data is well developed, if there is biological plausibility, and if it appears to be unbiased, we obviously should examine it. But right now, it appears that HPV vaccine anecdotes take precedence over massive studies.

And one more thing. Zoysia Chustecka needs to go back to journalism school and learn a bit about biased writing. About 90% of the article was quoting people who have an agenda against HPV vaccines. Let’s compare that to the 99% of the articles written about HPV vaccines that show it both safe and effective. If you’re going to write about medicine, try to get it right.

Notes

 

  1. The Blitshteyn article has been cited once, just once, over the past year (as of November 2015). That paper was penned by Lucija Tomljenovic, one of a pair of researchers, along with Charles Shaw, that publish bad research in horrible journals because they are paid to attack HPV vaccines. I’m connecting the dots for you.

Key citations:

 

 
 
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!