By Helen Petousis Harris 29/08/2015 11


The quadrivalent human papillomavirus vaccine called Gardasil is putting on a bloody good show and NO, it doesn’t cause THAT!

Despite strong evidence demonstrating effectiveness against a range of cancers and genital warts and robust data supporting its safety a bunch of silly rumours threaten to derail efforts to get our young women vaccinated. By the way boys should also be vaccinated but in NZ funding has not yet been provided for all our young blokes so most have to pay for it privately, inequitable yes – but that is another story.

So where does the evidence on effectiveness and safety stand in August 2015?

Gardasil is a very effective vaccine

As we know Gardasil performed extremely well in clinical trials, effectively preventing pre-invasive cervical lesions, and the results suggested it would have a dramatic effect on cervical disease and genital warts. While it is still very early days to be looking at cancer outcomes there are already reductions in cervical disease, such as cervical intraepithelial neoplasia (CIN), being observed.

Q: So now that it has been in use in various countries, what impact in the real world is it having?

A: Rates of cervical dysplasia are decreasing. Some examples below.

  • Californian data show a reduction in leisions caused by HPV16/18 classified as CIN2 or worse of 53.6% to 28.4% in vaccinated women who received at least one dose of vaccine. There was no reduction observed among unvaccinated women. The effectiveness increased as the time between vaccination and diagnosis increased.
  • Canadian data show a relative reduction in cervical dysplasia of 44% in young women who were vaccinated.
  • Australian data show any number of doses associated with a reduction in rates of high and low grade dysplasia and this effect gets bigger as more time goes on.

Q: What about warts?

A: Rates of genital warts are dropping in female cohorts eligible for vaccination and their sexual partners. Here is a recent systematic review.  And Australia have almost eliminated them.

Gardasil is a very safe vaccine

Now that around 180 million doses have been distributed what is the safety profile of HPV vaccine?

It is fair to say there is now a vast body of evidence about the safety of HPV vaccines. When I say vast here are some numbers.

  • Years of study – Clinical studies began ~2002 and are on going = 13 years
  • Number of studies since the vaccine was licenced – 9 years
  • Number of post licensure safety studies (2006 onwards) as of mid-2015 – 15 studies
  • Number of individuals in the studies – over one million
  • Who has been studied? – males and females aged 9 years to 45 years including people with special conditions such as pregnant women.
  • What are the risks from the vaccine other than minor stuff? Fainting is a real risk as is anaphylaxis

The bottom line is that when vaccinated people are compared with unvaccinated people there are no increased risks for serious adverse events. Put another way, receipt of 4-HPV vaccine does not increase your risk for a serious adverse event over and above your risk without having the vaccine. I think I have said this until blue in the face.

Blue in the face

Despite the now vast body of safety data there continue to be some pretty outrageous rumours that circulate – usually recycled rhetoric. Here are some of the myths around the safety of HPV vaccine and reasons why these claims are fallacious in some way.

Falsehoods about the safety of HPV vaccine – no it doesn’t cause that

Complex regional pain syndrome (CRPS).

CRPS can follow a minor injury. There are case reports in the literature of CRPS following needle related procedures including venipuncture and injections such as immunsiations. It is certainly important to be aware that even though rare, CRPS can occur after immunisation and also that young adolescent girls appear at highest risk. Some cases from Australia were published in 2012 and the authors provide a considered discussion on the matter, also noting that the cases responded to treatment and further doses were recommended and well tolerated.

However, this issue appeared to take on a life of its own in Japan leading to wide spread loss of confidence in the vaccine mid 2013 following highly publicised claims about adverse events. The public discussion grew with vocal anti vaccination proponents gaining control of the conversations and coordinating activities. Some medical professionals have also added their voices to the dabate, despite the fact there is no evidence that the vaccine has anything but a rare role in this syndrome. While the Japanese government no longer actively recommends the vaccine it is still available. The events in Japan are well documented in this report from the CSIS Global Health Policy Centre. and a source of great disappointment for the Japanese Ministry of Health.

Many major international newspapers and magazines are running stories about girls experiencing a range of neurological symptoms after receiving the vaccine. The Independent is one such example that has made waves here in NZ.

There is currently nothing to substantiate a significant causal relationship between HPV vaccine and CRPS other than the potential for minor needle related mechanical injury which, in rare instances, may result in CRPS in the arm. This letter to the Archives of Internal Medicine highlights the points nicely.

Studies that have assessed neurological events following HPV vaccine include a register based cohort study from Denmark and Sweden including 997,585 girls aged 10-17 of whom 296,828 had received a total of 696,420 doses of Gardasil. You would think that if this vaccine was the cause a bunch of CRPS it would show up here. But it does not. 

Commentary by CDC authors and summary of US passive safety surveillance data find no patterns to suggest an association. And, The Global Advisory Committee on Vaccine Safety have investigated and reported on all safety concerns that have been raised. They have found no evidence for CRPS (or any other conditions).  And finally, The European Medicines Agency are about to review the matter.

A review summarising the safety of Gardasil from 2006 – 2015 concludes:

Conclusions: These results, along with the safety data from the prelicensure clinical trials, confirm that the HPV4 vaccine has a favorable safety profile. Key policy, medical and regulatory organizations around the world have independently reviewed these data and continue to recommend routine HPV vaccination.

So while it appears to me that there is the fairly rare potential for needle related procedures to induce a CRPS the current rumours about HPV vaccine induced CRPS seem blown out of all proportion and effectively constitute a public health menace rather than a useful contribution to science-based evidence.

Aluminium adjuvant

A particularly wacky theory is that the aluminium adjuvant in the vaccine somehow colludes with viral DNA and/or viral proteins and/or yeast, crosses the blood brain barrier and/or induces an inflammatory reaction leading to ….death and disability. I have previously written about this [here] and will not go into it again here HOWEVER, the barn door most basic question you have to ask yourself is this: If the vaccine ingredients conspire to induce death and disability then surely we would see more death and disability in vaccinated people when we compare them to unvaccinated – after all presumably this will not happen in the unvaccinated? Wouldn’t ya think???

Surely that should be the end of the conversation. Risk the same regardless of vaccine exposure.

Postural Orthostatic Tachycardia Syndrome (POTS)

POTS is basically a condition that gives you a racing heart when you stand up. It can sometimes be associated with a viral illness. Some case reports have appeared in the literature following HPV vaccine, a couple of bottom level dwelling evidence examples below.

In 2013 a report of 6 cases was published, onset 6 days to 2 months following HPV vaccine. An autoimmune aetiology was proposed. In a 2015 report 21/35 women tested for suspected POTS fulfilled the diagnostic criteria. The time to onset of symptoms ranged from 0 – 30 days following HPV vaccine and a mean time to being tested for the condition 1.9 years. An autoimmune aetiology was proposed. Mmmm. Personally I find the whole autoimmunity argument a bit of a catch all for anti-vaxers as it is hard to argue against the possibility of biological plausibility no matter how improbable.

However…

Like the CRPS discussed above these are simply case reports which are hypothesis generating – we could pose a research question and then test it based on these case reports. That is called science.

And right now the actual real science says that no more bad stuff happens in people who have received HPV vaccine than happens in people who have not. 13 years down the track of HPV vaccination and the scientific evidence supporting the safety of Gardasil only got stronger. Unfortunately so did the wave of unsubstantiated rumour and scaremongering.


11 Responses to “HPV vaccine Gardasil – seriously good data reinforce its safety”

  • Hello Helen. I really appreciate your blog. It is refreshing to read material which focuses on the veracity of key vaccine related issues. Nevertheless, may I say, that I do find one aspect of your blogs somewhat unsettling; the manner in which you belittle any authors, publications, professionally published material with which you disagree. Frankly –
    to me at least – it undermines your credibility. Understanding, of course, that it is your personal blog, and you are perfectly free to write in whatsoever manner of style you wish!

    The truth around safety, efficacy, neurotoxin adjvants, suppressed test results, adverse effects and such, really does seem to be masked by a range of agendas. The extent to which say, Gardisil has been subject to the push and pull of agendas is surprising. The thing is, that parents, want valid information of high integrity in order to make informed decisions. And this requires balance i.e. the good, the bad – and the ugly. It is not sufficient (for some of us) to simply believe the statement “that Gardisil is a very safe vaccine”. True informed consent requires more than this I believe.

    A good example, is this article from ‘Childrens Medical Safety Research Institute’ – which throws decent balance to a couple of your sweeping statements. See below. “Death rate from cervical cancer in 9-20-year-old girls is zero and long-term benefits are yet to be proven,” say the immunologists. They cite unusually high adverse event reports with the vaccine, including cases of many autoimmune diseases such as paralyzing Guillain Barre syndrome, multiple sclerosis and transverse myelitis and state that “short-term risks to healthy subjects can prove to pose a heavier burden than cervical cancer.”

    Perhaps there is not sufficient resource to maintain healthy assessment to all new research (within Government departments). Perhaps the weight of money from within the Pharma industry is overwhelming. I dont have sufficient insight to know. What I do know, is that there is not sufficient balance, credence or worthwhile public debate given to the Downside risks associated with vaccinations .. Sincerely

    http://info.cmsri.org/the-driven-researcher-blog/on-vaccines-adjuvants-and-autoimmunity

    • Hi David,
      It is true I am scathing of certain material, something i will not apologise for because of the damage to public health such material can do (extreme example Wakefield). However, it is not because I disagree with the material per se but that it is dishonest and misleads. The link you provide is a perfect example. The Children’s Medical Safety Research Institute is an anti vaccination group, not a science group. The funder has been known to state “Vaccines are a holocaust of poison on our children’s brains and immune systems” Science plays no role here, in fact the science advisory board includes some well known pseudoscientists. Some of the research has been retracted from journals, some is published in journals on which the authors are editors (not necessarily a problem but it is a theme here rather than an exception. Here is a link to a discussion about the source of some of this material from the CMSRI, saves me from saying much the same thing. What is the difference between this antivax funded ‘research’ and big pharma funded research you may ask?

      There are many vaccine studies funded by industry and if all vaccine studies were funded by industry that would not be good. Just as well they are not. The industry funded studies are subjected to peer review from conception, ethical approval, progress reporting, and publication. However, the most important thing is that the findings are reproduced by studies funded by non-industry/non-profit entities such as public good and regulatory agencies. The antivax funded studies are not, they are generated by the same people over and over again.

      To directly respond to your comment “Death rate from cervical cancer in 9-20-year-old girls is zero and long-term benefits are yet to be proven,” say the immunologists. They cite unusually high adverse event reports with the vaccine, including cases of many autoimmune diseases such as paralyzing Guillain Barre syndrome, multiple sclerosis and transverse myelitis and state that “short-term risks to healthy subjects can prove to pose a heavier burden than cervical cancer.”

      Of course the death rate from cervical cancer in 9-20 year olds is virtually zero! They need a persisting infection with HPV for years to develop cancer, this is what the vaccine prevents. Quite frankly this is an issue for epidemiologists and oncologists anyway. The claim that the vaccine causes these terrible adverse events is just plain wrong and I will shamelessly launch attacks on those who deliberately mislead on this matter. How on earth can you hold up a poorly conducted laboratory study or voluntary online survey as evidence in the face of global population cohort studies and randomised clinical trials that include millions and repeatedly and robustly say otherwise? Obviously no scientist would.

  • Thank you for your reply Helen. You provide interesting perspective.

    Your comment that Children Safety Medical Research material is “dishonest and misleading” is interesting, in that the article I linked to also referenced several other organisations and (quite a bit of) peer-reviewed research. I wonder whether (or not) you read the articles, or pursued the referenced material.

    By proxy, you also besmirch the ‘Journal of Pharmacological Research’ and ‘Zabludwicz Centre for Autoimmune Diseases in Tel-Hashomer, Israel. And, you are sullying a number of other reputable institutions referenced in the article. Was this intentional? I am referring to these references:

    http://www.cmsri.org/global-research/ and
    http://www.cmsri.org/cmsri-funded-research/

    I respectfully suggest, that all the papers pertaining to adverse effects of adjuvants cannot all be “dishonest and misleading’. Indeed, I find intriguing that you (appear to) consider yourself a senteniel, with a mission to decry or denigrate any published research or material, which does not align with the position “that vaccines are very safe.” Speaking personally, I think that it undermines your credibility.

    I wonder whether (or not) you grasped my main point: that ” that parents, want valid information of high integrity in order to make informed decisions. And this requires balance i.e. the good, the bad – and the ugly. It is not sufficient (for some of us) to simply believe the statements such as “Vaccines are very safe”.

    We know that there are risks to vaccines, and that there are serious hospitalisation cases and life-changing events to a (small) number of people. Heck, the vaccine inserts acknowledge that much. We also know that the CDC itself acknowledges that only a small percentage of serious, adverse effects are recorded in the VAERS database. And, we know the history associated with the Smallpox and Polio cycles, and that the concept of ‘herd immunity’ only operates for some diseases. And, we know that there is immense pressure from Pharmacy advocacy and money to promote vaccines favourably.

    You see, we also know about the (Gardisil) scandals in Japan, Denmark and Australia. This stuff is public knowledge – and, goes against some of your (very public) proclamations.

    I respectfully contend that some of us have more insight than you presently give us credit for. To think otherwise is insulting. In order to uphold the principle of ‘informed consent’ in New Zealand, we require levels of integrity and transparency of the highest order.

    Sincerely, David Bernard

  • David – Some questions.

    “You see, we also know about the (Gardisil) scandals in Japan, Denmark and Australia. This stuff is public knowledge – and, goes against some of your (very public) proclamations.”

    Who is “we”?

    What event is it that you refer to as a “scandal”?

    Why did you choose the word “Scandal”?

    How does this paragraph stack up with your carefully (but obviously) contrived position as an honest broker?

  • Ashton. Greetings. Who is “we” ? Myself, and other intelligent parents, striving to peel back the layers of half-truth, pseudo science, fact and fiction, in order to arrive at a level of understanding, which allows us to make informed decisions.

    Why did I use the word “scandal” ? Because, the events I allude to, give appearance to satisfactorily full filling the definition of scandal: “an action or event regarded as morally or legally wrong and causing general public outrage”. I am happy to detail (but am giving you a quick response for now).

    Not quite sure what you mean by “How does this paragraph stack up .. honest broker”.

    The truth is, that I have growing admiration for Dr Helen, as I read her historic blogs. Perhaps she does indeed have a role as “Sentinel of knowledge”. Notwithstanding, in this whole matter of informed consent, parents such as myself are simply seeking factual, evidence based knowledge; the good, the bad, and the ugly – in order to make informed decisions. It aint easy !

    • Hi David.

      So we is an undefined group of people with limited (or no) medical background but a level of hubris that takes some beating, who are attempting to second-guess a group of professionals that numbers in the thousands.

      The only “scandal” I can find in your examples of countries and their reaction to Gardasil is the scandalous misinformation from the anti-vaxx lobby. Here is a neat and easy reduction of the facts vis-a-vis Japan.

      Ashton. Greetings. Who is “we” ? Myself, and other intelligent parents, striving to peel back the layers of half-truth, pseudo science, fact and fiction, in order to arrive at a level of understanding, which allows us to make informed decisions.

      https://www.skepticalraptor.com/skepticalraptorblog.php/japan-bans-gardasil-debunking-myths-hpv-vaccine/

      “parents such as myself are simply seeking factual, evidence based knowledge; the good, the bad, and the ugly – in order to make informed decisions. It aint easy ”

      Its actually pretty easy – there are many countries with reliable and well resourced medical research bodies, and they concur – vaccination is the best method we have for reducing or eliminating public health problems. They don’t concur because of shady backhanders, or a lack of insight. They concur because, dammit, its a fact.

  • David,

    If you are “simply seeking factual, evidence based knowledge”, then, mayhaps, you should first investigate the integrity, funding and veracity of CMSRI before professing your belief in their assertions.

    After all, that’s simply a small part of what scientists do when somebody, or some group, makes claims that are unsupported by the scientific consensus.

    After all, extraordinary claims require extraordinary evidence.

    Undoubtedly, you will disregard any research provided by pharmacological companies that supports the safety of vaccines (whilst, of course, wholeheartedly endorsing any research by them suggesting any degree of risk provided by those vaccines), but you appear to be unable to reverse the procedure.

    You do not seem to impart the same level of criticism to “research” funded by anti-vaccine agencies as you do to that funded by vaccine manufacturers.

    Yet the scientific method requires that you apply the same degree of scepticism to both sources of evidence.

    Please do so.

  • David,

    Helen told you that CSMRI is an anti-vaccine group, and why.

    I pointed out that whatever the source of evidence you use, the scientific method requires that you impart the same degree of scepticism to each source.

    I didn’t respond to your “key points”, since you can readily find others that can do so better than I am able. I responded instead to your statement that you are “simply seeking factual, evidence based knowledge” and advised you how using the scientific method allows you to do so.

    You should apply the same scientific standards to CSMRI that you apply to pharmaceutical companies.

    May I recommend a trio of books from Ben Goldacre for examples of how the scientific method can ensure you are finding “factual, evidence based knowledge”? “Bad Science,” “Bad Pharma” and “I think you’ll find it’s a bit more complicated than that” are all excellent books although allowances have to be made for their UK orientated content.

  • Firstly, thank you Ashton and Stuartg for your responses. Particularly, for the suggested ‘Ben Goldacre’ reading.

    I have realised that there is much to learn – and, indeed, from Dr. Helen’s archived, blog material.
    I have also realised that, not being a scientist, I am probably participating on the wrong blog.
    There is much ‘crazy stuff’ out there;

    https://worldmercuryproject.org/

  • You’re participating on the right blog. How you think about these things matters too, though.

    You need to genuinely consider that what you’re repeating really is “dishonest and misleading”! 🙂

    Well meant advocacy groups are rather good at fooling themselves. (Shades of Carl Sagan here, another author you might read – try The Demon Haunted World; I’ve got a blog post here with quotes from that, too!)

    A word about intellectual (dis)honesty might help. Intellectual dishonesty is not accusing people of deliberately lying or ‘cheating’. It’s about not holding up a proper care of duty in studying a thing. (I have a post on Sciblogs that touches on some of this, sparked by the retraction of one of the papers on aluminium adjuvants.)

    There are relatively few papers that claim a link between aluminium adjuvants and ‘harm’. Some groups exaggerate how many they are, unfortunately. Also, a closer look shows the arguments these papers offer aren’t nearly as good as these (advocacy) groups make out.

    As an extreme example, you might aware that Shaw and Tomljenovic’s work is often used to support a link between aluminium adjuvants in vaccines and autism. Are you aware that their latest paper has been retracted owing to ‘creatively edited’ images in the paper?

    Citing the vaccine inserts as ‘evidence’ is a common thing encouraged by some advocacy groups. There’s a lot to this, but the nutshell is that they can’t be taken simplistically. As a simple example, the Gardasil vaccine inset reports 40 deaths — from road accidents, drug overdose/suicide, gunshot wound, etc. The catch is that in large studies there will always be some deaths because people die all the time, and if you take a large enough group some will die.

    There are more subtle points, too. Correlations don’t imply the first thing caused the second, they only indicate they coincided. You have to do more work to show cause. It’s worth noting that a few ‘side effects’ were rarer in the vaccinated v. the placebo controls. It’s the nature of statistics have a few either way, just due to randomness.

    As an example, if you were “obliged” to take the Gardasil vaccine insert naïvely, you’d be obliged to conclude that Gardasil has a preventative effect against inflammatory bowel disease — that Wakefield so infamously tried to link to the MMR vaccine. (And perhaps it does – but you’d need more than what the insert shows.)

    There are studies looking into these things more closely. Bottom line is there are very few cases of serious harm (for want of a better term) that can be confirmed. That’s not to say these things never happen, but the effect is claims about them are too often exaggerate in at least two ways. One is to make out there’s more instances of harm caused than there is. Another is to over-simplifiy to “the vaccine what done it”, leaving out all the rest of the biology (and statistics!)

    A deeper problem is that the meaningful comparison for safety is NOT against no harm at all, but comparing against the harm the disease causes. Better the disease or the vaccine? Literally everything in life has hazards and risks (two different things). There isn’t a single thing you do that you can ask there is absolutely no hazard (or risk). Asking for that is asking for something impossible. Some advocacy groups ask for the impossible because tactically they know it’s unachievable. That’s intellectually dishonest, too. (Comparing against no harm at all is an ideal – we’d all like that, but we do have to remember we live in a real world!)