HPV vaccine clinical trials being attacked by anti-vaccine religion again

I have said this before, and I am becoming slowly convinced of my opinion on the matter – the anti-vaccine religion has a particular hatred for the HPV vaccine, usually Gardasil, that far exceeds its abhorrence of most other vaccines. Recently, Slate, generally a reliable source for vaccine articles, published an anti-vaccine screed against Gardasil that seems to be based on a claim of faulty HPV vaccine clinical trials.

As a result of some expected negative comments made about the article, Slate took the unusual step of trying to explain itself. I am not sure that they have gotten very far, even if the author of the explanation claims that they would get the Gardasil anti-cancer again. But they really have concerns about the HPV vaccine clinical trials.

Well, I do not have those issues regarding the HPV vaccine clinical trials. First, the author of the original article is simply an amateur about science, clinical trials, and statistics. The author was trying to create doubt about the Gardasil vaccine based on misunderstanding, at best.

Second, the author fails to grasp that vaccines are constantly monitored by post-marketing studies that often include huge numbers of patients, which can find very rare instances of adverse effects. In these studies, nothing was found that tied Gardasil to anything serious, short of fainting by patients after getting the shot, a common occurrence with patients.

Third, the author relies on anecdotal evidence, which has zero value in scientific understanding. This is a serious issue that should have cause Slate to back off from the article.

But Slate didn’t. And here we are. We’re going to critically examine what they wrote, but mostly I’m going to focus on the numerous large patient studies that completely refute their claims. Slate’s anecdotes and misunderstanding of clinical trials versus scientific data – guess which wins?

All about HPV vaccines

I know, I’ve written about this vaccine 100 times, so you’ve read the following few  paragraphs enough times to quote them without looking. Actually, I add information as necessary to make sure you have up-to-date facts and figures about the HPV vaccine.

However, for some of you, this might be your first bit of research into the human papillomavirus (HPV) vaccine, so it’s important to get a brief overview of HPV and the vaccines. If you’ve read this before, just skip to the next section if you want.

Genital and oral  HPV are the most common sexually transmitted infections (STI) in the USA. There are more than 150 strains or subtypes of HPV that can infect humans, although only 40 of these strains are linked to a variety of cancers. HPV is generally transmitted from personal contact during vaginal, anal or oral sex.

Although the early symptoms of HPV infections aren’t serious, those infections are closely linked to many types of cancers in men and women. According to current medical research, here are some of the cancers that are linked to HPV:

These are all dangerous and disfiguring cancers that can be mostly prevented by the HPV cancer vaccine. If you’re a male, and you think that these are mostly female cancers, penile cancer can lead to amputation of your penis. Just think about that guys.

HPV is believed to cause nearly 5% of all new cancers across the world, making it almost as dangerous as tobacco with respect to cancer. According to the CDC, roughly 79 million Americans are infected with HPV–approximately 14 million Americans contract a new HPV every year. Most individuals don’t even know they have the infection until the onset of cancer. About 27,000 HPV-related cancers are diagnosed in the USA every year.

There were two HPV vaccines on the market before 2014. GSK, also known as GlaxoSmithKline manufactured Cervarix, a bivalent vaccine, but it has been withdrawn from the US market, because of the competition from the other HPV vaccines. In Europe and other markets, Gardasil is known as Silgard.

Merck manufactures the other HPV vaccines. Its first vaccine, the quadrivalent Gardasil, targets the two HPV genotypes known to cause about 70% of cervical cancer and two other HPV genotypes that cause genital warts. The newer Gardasil 9, approved by the FDA in 2014, is a 9-valent vaccine. It targets the four HPV genotypes in the quadrivalent version, along with five additional ones that are linked to cervical and other types of cancer. Both versions of Gardasil are prophylactic, meant to be given before females or males become exposed to possible HPV infection through intimate contact.

Slate’s claims about HPV vaccine clinical trials

The article, “What the Gardasil testing may have missed,” was written by Frederik Joelving, a Danish journalist. As far as I know, Joelving has no academic or research expertise in vaccine science, but that rarely stops a journalist from commenting on HPV vaccine clinical trials.

Joelving did an eight month investigation and became convinced that there were serious flaws in HPV vaccine clinical trials that were submitted to the European Medicines Agency (EMA), the agency that reviews medicines, such as vaccines, for the European Union. Joelving thinks he has uncovered evidence that there was some sort of malfeasance on Merck’s part with respect to Gardasil’s clinical trials.

Joelving makes this claim:

To track the safety of its product, the drugmaker used a convoluted method that made objective evaluation and reporting of potential side effects impossible during all but a few weeks of its years long trials.

In an internal 2014 EMA report about Gardasil 9 obtained through a freedom-of-information request, senior experts called the company’s approach “unconventional and suboptimal” and said it left some “uncertainty” about the safety results.

This sounds serious. As best as I can tell Joelving’s bases his claim on a review, that was initiated at the request of Denmark (countries can make requests of European regulatory agencies to undergo reviews of drugs), to look at two conditions that many people have attempted to link to Gardasil. Those conditions are:

  • 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,

The EMA states 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.” The EMA clearly dismissed any claims of a causal link between the HPV vaccine and those two conditions.

The suspicion that postural orthostatic tachycardia syndrome is related to a study published earlier in 2015 by Danish researchers who provided some observational evidence about POTS occurrence after HPV vaccines. This study was seriously flawed – I strongly critiqued this study previously.

My essential points were that it was a case study, not a controlled clinical trial. Case studies rank pretty close to the bottom of the hierarchy of scientific studies. And that POTS is notoriously difficult to diagnose accurately. This doesn’t qualify as strong evidence that the HPV vaccine is related to POTS. Not even close.

Similarly, there is no evidence of a causal relationship between the HPV vaccine and CRPS, which seems to have arisen from a paper that hypothesized a relationship, without any clinical evidence. Except for the aforementioned anecdotes.

The larger problem with Joelving’s article is that he loves anecdotes from individuals who could not possibly establish a link between the vaccination and their conditions. They make for compelling stories – but they make for really bad science.

EMA responds to the POTS and CRPS claims

Of course, the European Medicines Agency, two years ago, responded to the claims, similar to the ones that Joelving made. Let’s just say there’s one side with opinion and anecdotes, and the other with firmly established science.

In November 2015, the EMA determined that HPV vaccines are not linked causally to the development of either POTS or CRPS. The agency concluded  that observations of POTS and CRPS after HPV vaccination are not different from the rates that would be observed in the general population of these demographic groups.

Here are some excerpts from their statement:

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.

PRAC thoroughly reviewed the published research, data from clinical trials and reports of suspected side effects from patients and healthcare professionals, as well as data supplied by Member States. It also consulted a group of leading experts in the field, and took into account detailed information received from a number of patient groups that also highlighted the impact these syndromes can have on patients and families.

Their reasoning was not based on some undue influence from Merck or anyone’s opinion. It was based on robust scientific evidence that overwhelmingly supports the lack of a causal relationship:

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.

If you don’t have the time to read all of PRAC’s reasoning for dismissing these claims, let’s get to their final conclusion:

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.

Let me digest this down to the simplest terms – Joelving’s claims are based on anecdotes and case studies which did not meet the standards of of valid HPV vaccine clinical trials. And certainly did not meet any standard that would require a change in EMA’s regulations for Gardasil.

The post-marketing HPV vaccine clinical trials

As opposed to the beliefs of Joelving, science is not static and dogmatic. Pharmaceutical companies have a responsibility, by law and tradition, to continue clinical trials for their products. And this is true of Gardasil.

There is a literal boatload of data that has been reviewed in case controlled studies on Gardasil. Some of these are huge studies with millions or hundreds of thousands of patients. These are studies so large that even the smallest adverse event could be statistically identified if it were more common than the background rate.

Let’s take a look at a few of them:

These studies did not find increased risks of POTS or CRPS. They did not find anything that has been claimed by the anti-vaccine religion or Frederik Joelving.

Unsurprisingly, Joelving jumps on the argument from ignorance, claiming that the anecdotal evidence leads one to believe that,

Not owning up to that uncertainty, when it is legitimate, likely will only slow scientific progress. In the controversial realm of vaccines, it will also create fodder for conspiracy theorists spreading overblown or unfounded fears among an already distrustful public.

Is Joelving writing about himself? His whole a article is based on cherry picking really bad information, that sounds like he is trying to create a manufactroversy – using information that has been long disputed and refuted.

One more thing – Slate makes excuses

As I mentioned above, Slate, probably to deflect lots of criticism, wrote an accompanying “here’s why we published this junk science article” opinion piece. Here’s what they concluded:

If this story were about almost anything besides a vaccine, I doubt I would be writing this. The value of understanding potential side effects and ensuring that our clinical trials are robust enough to do so would be apparent, I suspect. But because it is about a vaccine, this is much more complicated, because there’s a (legitimate) fear that this story could be used to bolster a case that vaccines are bad and untrustworthy. And bolstering that case could have real and serious ramifications for public health if it leads to more people not getting vaccinated.

Here’s the problem with your making excuses about a bad article on Gardasil – there were no scientific facts presented. None. Sure there was cherry picking and anecdotes, but they do not form the basis of scientific knowledge.

Joelving completely ignored (or, at best, briefly mentioned), the numerous large and compelling studies that are great science. And clearly makes a legitimate case that the vaccines are extraordinarily safe. Slate makes it sound like Joelving made a case – he didn’t. He reiterated the lies and misinformation of the anti-vaccine religion, which means that Slate aided and abetted the disinformation campaign about the HPV vaccine.

As Vaxopedia concluded about Joelving’s article:

Downplaying the risks of vaccine-preventable diseases, while trying to scare folks about vaccines – that’s what gets you labeled as anti-vaccine.

Yes Slate, you are now officially anti-vaccine. You get to fix that label by disowning Joelving’s junk science. Or not.  But reading your companion piece, it appears you have an arrogant belief that you are the science police. You’re not, unless you do a better job of avoiding logical fallacies, avoiding cherry-picking, and avoiding anti-vaccine tropes.

Gardasil prevents cancer. Gardasil is extremely safe. Gardasil saves lives.

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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!