This article was first published on 11 September 2016, but on foot of this week’s debate about the HPV vaccine, we are republishing. We have re-checked and, if necessary, updated all figures to ensure its accuracy. 

AS THE SCHOOL year begins, tens of thousands of girls in the first year of secondary school will be offered the HPV vaccine in Ireland.

But a campaign called Regret has come to prominence, questioning the safety of the vaccine, and claiming it caused illness in 400 Irish teenage girls and young women after they took it.

Jacqui Madden in Co Roscommon and Deirdre Lally in Co Wicklow asked us to look into their claims, and assess the safety of the HPV vaccine, so we did.

(Remember, if you see a social media campaign you’re not sure about, email factcheck@thejournal.ie or tweet @TJ_FactCheck).

Claim: The side effects of the HPV vaccine outweigh the benefits
Verdict: FALSE (by a very wide margin)

• Repeated studies and clinical trials have shown HPV vaccines like Gardasil to be very effective in preventing the virus which leads to most cervical cancers
• Repeated studies and clinical trials have shown HPV vaccines to be very safe, and potential allergic reactions and possible side effects to be extremely rare
• What little scientific research has been done contradicting this overwhelming consensus, has consistently been shown to be flawed and unreliable
• There is no evidence to show that the illnesses highlighted by the group Regret were caused by the HPV vaccine

THE FACTS

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The Basics

HPV stands for Human Papillomavirus, which is one of the most common sexually transmitted infections, with almost all men and women contracting it at some point in their lives.

According to the HSE, 80% of women contract HPV, usually in their late teens or 20s.

In most cases, the virus clears on its own and does not have any symptoms, but in some cases, it can lead to genital warts. In women, HPV can cause changes in the cervix (the lower part of the uterus, or womb) which can lead to cervical cancer.

The HPV vaccine used in the school programme is called Gardasil, and protects against four out of 170 types of the virus: numbers 6, 11, 16, 18.

However, 16 and 18 alone are responsible for 70% of cervical cancers, as well as 75-80% of anal cancers, according to the manufacturer’s package leaflet and the Health Protection Surveillance Centre.

This fact wasn’t taken into account in the misleading claim made by Regret:

The HPV vaccine will not save any lives on its own merit, as it only protects against 4 strains out of more than 100 HPV infections.

The fact is that two of those four strains account for 70% of cervical cancers, and an immunisation against them therefore necessarily prevents some cervical cancer development, and therefore saves lives.

The rate of cervical cancer among women in Ireland is one in 115 (0.87%), according to the latest figures (for 2016).

In Irish schools, the HSE began administering a programme of HPV vaccination for free in May 2010, in schools and in clinics, to girls in first year of secondary school, and later began a “catch-up” programme for sixth years.

This previously involved three injections separated by six months each, but since the 2014/2015 academic year, has been decreased to two injections, six months apart.

Parents and guardians are given this HSE information booklet, and asked to sign a consent form before the vaccine can be administered.

In the 2014/2015 academic year, 55,121 vaccine doses were administered. In 2015/2016, 48,682 vaccine doses were given.

Gardasil is manufactured by Merck and was authorised by the Irish Health Products Regulatory Authority (HPRA) in September 2006, after being licensed by the European Medicines Agency.

The other HPV vaccine licensed in Ireland is Cervarix, which is manufactured by GlaxoSmithKline. Both are “prophylactic” medicines, which means they prevent HPV for a number of years after being administered, but do not cure it in existing cases.

Effectiveness of the HPV vaccine

There is an exceptionally large volume of scientific research on the efficacy of HPV vaccines, which include Gardasil.

A good place to start is this World Health Organisation (WHO) review of studies, which reported the vaccines had an efficacy rate of between 90% and 100% in preventing HPV infection.

A 2011 meta-analysis evaluated the results of seven separate randomised control tests, and found – for various groups of women over various time periods – the efficacy rate of the vaccines was 96%, 90%, 53%, 84%, 94%, 95%, 85%, 76%.

A 2014 meta-analysis evaluated the results of 15 previous scientific studies – 10 randomised control tests and five observational studies.

It found the effectiveness of the vaccines in preventing HPV 16 and 18 (the two most serious strains) ranged from 83% to 94%.

Another 2014 meta-analysis, on the long-term effectiveness of Gardasil, found that in one study of more than 1,000 vaccinated boys and girls aged 9-15, there wasn’t a single HPV infection up to nine years later.

And in another study where women aged 16-23 were vaccinated, there wasn’t a single HPV infection five and nine years later.

Finally, the original clinical trials which were the basis for Gardasil being licensed, found the vaccine was effective in 88.7% of cases (page 12/13, here).

Safety of the HPV vaccine

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Ireland

From 2010/2011 to 2014/2015, some 590,694 doses have been administered to first and sixth-year female secondary school students in Ireland, according to FactCheck’s analysis of data collected by the Health Protection Surveillance Centre (HPSC).

The total number of girls who took the full set of Gardasil doses available was 201,410.

Between 2010 and 2015, a total of 948 “adverse reactions” to Gardasil were reported to the HPRA.

Adverse reactions are, essentially, negative symptoms perceived to be side effects from a drug. According to a parliamentary question response by then Health Minister Leo Varadkar, in January:

The vast majority of reports received have been consistent with the expected pattern of adverse effects associated with use of Gardasil, as described in the product information.

These include reactions associated with the administering of the vaccine itself (an injection) like fainting, dizziness, headaches, skin rashes, but also include:

Chronic fatigue, nausea, swollen joints, gastrointestinal problems, drowsiness, menstrual disorders.

958 reports of negative reactions (of varying degrees of severity) out of 590,694 doses constitutes 0.16%.

If we plot those figures on a chart, the number of adverse reports is actually invisible compared to the scale of the doses administered.

And it’s important to note that these are simply reports of adverse reactions – they do not, by any means, constitute proof that the administering of the vaccine was the cause of the symptom.

Furthermore, some of the 108 adverse reports in 2015 would have related to the 2015/2016 vaccination programme, which is not included in the number of doses.

Europe

In November 2015, the European Medicines Agency published the results of a major review of the safety of HPV vaccines including Gardasil and Cervarix, examining an alleged link to two conditions.

They were: complex regional pain syndrome (CRPS), a chronic pain syndrome which affects limbs; and POTS (postural orthostatic tachycardia syndrome), which involves rapid heart rate increases on sitting or standing up, along with fatigue, dizziness and other symptoms.

The largescale EMA review concluded that there was no causal relationship between the HPV vaccines and the two conditions, and that, essentially, the prevalence of those two conditions was no greater among those treated with the vaccines, than among the general population.

It recommended no change to the licensing terms or product information requirements of Gardasil and Cervarix.

Package information

The manufacturer’s leaflet, which is reviewed by the HPRA, states the following possible side effects of Gardasil:

• Very common (more than 10% of patients) – Pain, swelling, redness at the injection site, headaches
• Common (more than 1%) – Bruising, itchiness at the injection site, fever and nausea
• Rare (less than 0.1%) – Hives
• Very rare (less than 0.01%) – Wheezing, difficulty breathing

Scientific research

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Once again, very many scientific studies and reviews have been conducted on this, and have found HPV vaccines like Gardasil to be extremely safe.

One of the 2014 meta-analyses mentioned above evaluated a 2013 study of almost one million 10-17 year-old girls in Denmark and Sweden.

It found no difference between vaccinated and unvaccinated girls in the rate of what have been claimed to be serious adverse effects – various autoimmune and neurological conditions, as well as venous thromboembolism (VTE), which includes deep vein thrombosis.

Another study from 2014 analysed 42 completed or ongoing clinical trials of Cervarix and found that the rates of symptoms were almost identical between vaccinated and control groups.

In fact, the rates of “medically significant conditions” and “serious adverse events” were slightly lower among the vaccinated groups, not that any particular conclusion should be drawn from that.

This summary of nine separate studies involves research into possible associations between HPV vaccines and a wide range of conditions and symptoms, including serious ones like stroke, appendicitis, and Guillain-Barré syndrome, an immune disorder that causes weakness and even paralysis, and has been claimed to be caused by HPV vaccination.

In almost all cases, the research found no difference between vaccinated and control groups in the prevalence of the conditions, with the exception of temporary problems like fainting and skin irritation.

In one case, a lower “odds ratio” (essentially a lower risk) of multiple sclerosis was observed among the vaccinated group.

In the case of Guillain-Barré syndrome, the rate of reported cases was 0.2 per 100,000 doses of Gardasil. That’s one in half a million, or 0.0002%. And that rate was no higher than is typical of other vaccines.

Yet another 2011 systematic review of existing research concluded that the prevalence of serious adverse events was not different between vaccinated and control groups.

And finally, another 2011 systematic review found the same results.

Regret’s evidence

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FactCheck asked the group Regret to provide evidence to support the contention that the HPV vaccine caused the health problems suffered by the 400 young women it represents, and that the HPV vaccine is not safe.

A spokesperson for the group confirmed it was their view that “on balance, the risks of taking the HPV vaccine outweigh the benefits”.

On the question of a cause-and-effect relationship, the group told us:

We question the safety of the vaccine, but without the appropriate independent investigative tools, we cannot establish the causation link [sic].

They did not provide any evidence showing that Gardasil caused the health problems observed among the girls in question.

On the wider question of the safety of Gardasil in general, Regret directed us to articles reporting decreasing uptake of the vaccine in various jurisdictions, and criticism of it, but only one scientific study.

The fact that uptake of the vaccine is decreasing in a small number of countries, or that its safety has been questioned, does not, of course, constitute evidence that it is not safe.

And in reality, the Canadian study highlighted by Regret does not give any support to their contention – quite the opposite. Its authors even expressly stated that the rate of side effects following HPV vaccination was “low”.

The research, published in April 2016, tracked the rate of AEFI (adverse events following immunisation), as well as hospitalisation and emergency department admissions within 42 days of vaccination, among women and girls aged nine and older in the Canadian province of Alberta, between 2006 and 2014.

In 99.2% of cases, the HPV vaccine administered was Gardasil.

The study found:

• Out of 528,913 doses of a HPV vaccine, 198 adverse events (side effects) were reported. That’s 0.04%
• Out of 195,270 girls and women vaccinated, 192 reported adverse events. That’s 0.1%
• Of those 192, four reported an adverse event serious enough to warrant hospitalisation within 42 days
• Therefore, four out of 195,270 vaccinated individuals experienced a serious side effect following vaccination. That’s 0.002%
• Of the 198 adverse events reported, the outcome was known for 171. All 171 ended in full recovery
• Of the 195,270 patients vaccinated, 958 (0.49%) visited the hospital within 42 days – 35.3% within two weeks, and 64.7% after two weeks
• Only four of these had reported a side effect from the vaccination
• Of the 195,270 patients vaccinated, 19,351 visited the emergency department (ED) within 42 days. That’s 9.9%

Regret presented the fact that almost 10% of those vaccinated visited the ED within 42 days as evidence supporting the risks of the HPV vaccine.

But this ignores the fact that only 0.002% of those vaccinated reported a serious side effect (one warranting a trip to the hospital).

In other words, those hospital and emergency department visits were not linked to the vaccination, not even in the minds of the women and girls themselves.

The “Research” page of the group’s website contains mostly op-ed articles, speeches or interviews criticising the vaccines, but among the more substantive items listed are:

• An article which claims clinical trials of Gardasil and Gardasil 9 showed a rate of serious side effects of 2.5% and 2.3%.

On even cursory examination, this is very misleading. In reality, between one month and four years after vaccination, only four out of 15,705 individuals had a side effect that was determined to be vaccine-related. That’s 0.03%.

Once again, vaccinated people getting sick in the normal course of events (including up to four years after vaccination) is falsely being presented as caused by vaccination.

• A Danish study which described a pattern of “autonomic dysfunction” (problems with breathing, heartrate and digestion) among 53 vaccinated patients.

It noted that it could not confirm or dismiss a causal link with the vaccine, but called for further research. However, the consistency of the symptoms observed is surely due to the fact that:

This was a retrospective analysis based on 75 patients consecutively referred to the Syncope [Fainting] Unit from May 2011 to December 2014 for a head-up tilt test due to 
orthostatic intolerance and symptoms compatible with autonomic dysfunction as suspected side effect following vaccination with the Q-HPV vaccine.

In other words, the study found a strong pattern of autonomic dysfunction among a few dozen patients who were referred to a specialised unit, with symptoms of autonomic dysfunction. Which is hardly shocking.

• A 2012 study which concluded that certain HPV vaccines “pose an inherent risk for triggering potentially fatal autoimmune vasculopathies [blood vessel disease]“.

That alarming conclusion was based on autopsy analysis and tissue samples taken from the brains of two young women (19 and 14), who had died six months and two weeks after HPV vaccination.

The study was so alarming that the US government’s Centers for Disease Control (CDC) established a working group to examine it. In a public response, they found several serious flaws:

• The authors’ diagnosis of cerebral vasculitis (blood vessel inflammation in the brain) was invalid
• The way they tested for the presence of vaccine-related proteins lacked proper controls and was “questionable”
• The authors did not use the right equipment to properly identify vaccine particles, and did not use control samples, so the relevance of what they did find “cannot be determined”
• They did not present enough information to be able to examine possible alternative causes of death.

And for the record, out of the many millions of HPV vaccine doses administered in the US over the years, the CDC working group found one report of cerebral vasculitis (the disease the article claims is caused by the vaccine), 45 days after a vaccination.

And that was in a woman who already had immune system difficulties and several medical problems to begin with.

In the medical literature, they found two cases of vasculitis after vaccination (neither of them in the brain, which is the focus of this study), and both of them attributed to a blood vessel disorder called Henoch-Schonlein Purpura.

Conclusion

• A very large number of clinical trials and scientific studies, some outlined above, have proven HPV vaccines, including Gardasil, to be highly effective in preventing the virus that causes 70% of cervical cancer
• These trials and studies have also proven HPV vaccines, including Gardasil, to be very safe, with extremely low rates of serious possible side effects
• What little scientific research has been done contradicting this overwhelming consensus, has consistently been shown to be flawed and unreliable
• There is no evidence whatsoever that HPV vaccination caused the health difficulties observed among the 400 young women represented by the group Regret

The claim that “On balance, the risks of taking the HPV vaccine outweigh the benefits” is FALSE by a very wide margin. In fact, the evidence is unequivocal.

Send your FactCheck requests to factcheck@thejournal.ie

Update: This article has been updated to include the fact that the cervical cancer rate among women in Ireland is one in 115, according to the latest figures (2016).

Correction: This article has been amended with the correct spelling of the HPV vaccine Cervarix. We previously wrongly referred to it as “Cervatrix”.

This article was originally published on 11 September 2016