By Helen Petousis Harris 29/08/2015


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.


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