By Rob Verkerk PhD, executive and scientific director
Few would argue that the HPV vaccine is not contentious. That’s why uptake rates for 12 to13 year-old schoolgirls varies considerably from one geographic location to another. In the UK, while the average is close to 90%, in at least one region (East Sussex), uptake is around half this average.
Those who don’t consent to the vaccine are exercising their democratic and legal rights. The government and the bulk of the mainstream medical profession argues these people are acting irrationally or have been misinformed. Vaccine protagonists tend to see the HPV vaccine as something of a panacea for cervical cancer that also saves society money downstream — with no significant downside or risk.
But if you’ve dug deeper into the science and politics of HPV vaccination, as we have, or experienced a serious side effect, or are a parent of a child who has, would you agree? How common or serious is a ‘serious side effect’ anyway? And, are parents and children given sufficient information to be able to give informed consent prior to the arrival of nurses at schools to deliver their course of two or three HPV jabs as part of the national immunisation programme?
The debate has really heated up in the UK again, prompted by some new, publicised cases of suspected adverse reactions in young teenagers in The Independent and Daily Mail on 31 May and 1 June, respectively. On the back of this, the government is trying hard to increase uptake rates of the vaccine in those counties, such as East Sussex and Cornwall, where rates have been lowest.
Over the last two days I’ve been invited by BBC television and radio to air my views on this issue, questioning especially whether sufficient information is being provided to girls and parents to allow informed consent.
Following are some of the key questions that many people want to know about before giving consent for the HPV vaccine. We hope the answers we’ve provided help you to make a more informed choice.
Much of the background on HPV and cervical cancer is both well known and generally undisputed. Some of the main facts are as follows:
Persistent infection with particular strains of the Human Papilloma Virus (HPV) is responsible for the vast majority of cases of cervical cancer; high-risk HPV types (including types 16 and 18) are detected in 99% of cervical cancers
Around 120 HPV types have been identified in total, with about 40 of these infecting the mucosal epithelium. Of these, types 16 and 18 are among the high-risk types that are responsible for high-grade cervical cell abnormalities that are precursors to cancer and anogenital cancers
Long-term infection with types 16 and 18 are responsible for about 70% of cases of cervical cancer
Long-term infection with types 16, 18, 31 and 33 are responsible for around 80% of cervical cancers
In about 90% of cases of infection, the infection naturally resolves within 2 years, with the virus being overcome by the immune system
Globally, HPV infection and cervical cancer risk is significantly higher in developing countries, as compared with developed ones. Around 85% of deaths from cervical cancer occur in developing countries. This may be associated with concomitant risk factors such as smoking, the number of sexual partners and infection with HIV, as well as low levels of screening, less access to treatment and poorer outcomes from treatment
Cervical screening by means of pap testing is recommended every 3 to 5 years (greater frequency for ages 21-30, lesser frequency when older) and provide a voluntary, useful and proven means of early diagnosis of cell abnormalities or high-risk HPV infection that, if left untreated, may lead to cervical cancer
Vaccination after infection with HPV (transmission being associated with sexual activity) has been shown to be completely ineffective, hence the targeting of 12-13 girls for the vaccine
Further information and references to published scientific studies can be found in UK, US and World Health Organization (WHO) guidance:
Cervical screening or pap smears are voluntary. The most comprehensive tests now detect both cell abnormalities in the cervix and presence of key HPV types, although the latter tests are more relevant for older women. The risk that persistent HPV infection with ‘high-risk HPV’ types (hrHPV), of which there are 13, will trigger cervical cancer is higher among younger women, especially those in their 20s. That’s why the US recommends that women between the ages of 21 and 29 are pap tested every three years and those between ages 50 and 64, every five years.
In the UK, the recommended starting age is slightly older, being 25, with a recommendation that screening is conducted every three years through to age 49. From ages 50 to 64, 5 yearly testing is recommended.
Also in the UK, results from screening show that 40% of women aged 20 to 24 are positive for one type or another of HPV, with 15% of these (just 6% of this age group) being positive for types 16 and 18. Annual incidence of cervical cancer ranges from around 2,500 to over 3,000 cases in the UK.
Given the arrival of rapid genetic sequencing techniques and a clearer understanding of the role of particular HPV types in the development of cervical and other cancers, there is a shift towards using detection of hrHPV as the primary focus for screening. This approach is being pushed hard by Prof Henry Kitchener, Chair of the Advisory Committee of Cervical Screening (Public Health England) and colleagues, who have been intimately involved with cervical screening for decades. They note also that cervical screening rates in the UK have declined in recent years, from 81.2% to 78.3% between 20013 and 2013. This decrease in uptake may be associated with the introduction and uptake of the HPV national immunisation programme.
Two principle vaccines have been created targeting HPV, commercially known as Cervarix and Gardasil. They use recombinant, genetic engineering techniques using yeast or insect cells that create ‘virus-like particles’. The vaccines don’t include any live or attenuated viruses or virus fragments themselves. Each of the two main vaccines use different adjuvants in their formulations, the adjuvants having been associated with a range of adverse reactions post-vaccination.
The divalent vaccine, Cervarix, manufactured by the UK’s GSK, the second largest pharma company in the world after Pfizer, targets only HPV types 16 and 18 that cause about 75% of cervical cancers. This vaccine was introduced in the UK in September 2008 and was used as part of the national immunisation programme until September 2012, when it was replaced by the quadrivalent vaccine Gardasil, manufactured by French pharma giant, Sanofi Pasteur MSD. Gardasil targets not only HPV types 18 and 18, but also HPV types 6 and 11 that are important mediators of genital warts.
The vaccination schedule in the UK has recently been shifted from three doses to two, where the second dose is given at least 6 months after the priming dose (if the child is under 15 years old) and not more than 24 months after.
The decision to switch from Cervarix to Gardasil was made in the knowledge that Gardasil saves public money and might improve quality of life, while Cervarix appears to reduce risk of death from cancer. Is it another case of money first?
GSK and Sanofi Pasteur were involved with the Prescription Medicines Code of Practice Authority (PMCPA) in their own dispute about the effectiveness of their respective vaccines back in 2008, and given lack of head to head comparisons and paucity of published data, it is difficult to make direct, scientifically meaningful comparisons.
Even if Gardasil was 100% effective in dealing with HPV types 16 to 18 (which it isn’t), it still neglects other HPV types that are responsible for around 30% of cases of cervical cancer.
There is very limited available evidence of how effective the vaccine is in practice.
The UK Department of health estimates that, “By immunising girls against HPV before they get infected…up to 400 deaths from cervical cancer every year could eventually[our emphasis] be prevented.”
We have been unable to find the source analysis for this work. Conspicuously, while it is cited regularly in NHS, MHRA and Department of Health reports supporting the national immunisation programme, the evidence base for the figure is not routinely given.
A UK study published in 2010, suggests a more conservative impact, with a prediction that just 145 lives per year among the key 20 to 29 year age group would be saved.
The often quoted ‘400 lives saved per annum’ figure was issued prior to the most comprehensive epidemiological study on the vaccine’s effectiveness, undertaken in Australia, and published in the British Medical Journal in March 2014. Australian adolescent girls have been exposed to HPV mass vaccination longer than any other population so the results are highly relevant and based on the real world, as opposed to clinical trial, findings. The authors found that Gardasil “provided 46% protection against histologically confirmed high grade cervical abnormalities” and “just 46% protection against hr-HPV types”, and “The numbers needed to vaccinate to prevent one cervical abnormality at first screening round were 125 for a histologically confirmed high grade abnormality”. Perhaps not quite as spectacular as many are made to believe – and we’ve given our readers direct quotations from the BMJ to ensure there is not any misinterpretation of the findings.
These figures must be viewed alongside the serious adverse event rate (see below) of 1 in 10,000, which equates to around 2,500 of the UK’s female population, assuming it was 80% vaccinated.
Vaccine take-up in the UK has actually been a little higher on average, at 87% (2013-14). Cornwall and East Sussex, by contrast, have typically had the lowest rates of uptake, with 57% and 49% respectively between 2013 and 2014. Low uptake has been the main reason for the recent push and associated media with which ANH-Intl has been involved in East Sussex.
Equally disconcerting, is that as shown by data provided to the US Food and Drug Administration (FDA) during the registration process for Gardasil, there is a 44.6% increased chance of being diagnosed with precancerous lesions if a vaccinated girl has been exposed to any of the HPV types in the vaccine prior to inoculation.
Cervical cancer incidence
In 2011, there were 3,064 new cases of cervical cancer in the UK. The crude incidence rate shows that there are around 10 new cervical cancer cases for every 100,000 females in the UK.
In 1990 there were around 12 case per 100,000, and this has reduced to about 9 per 100,000 currently. The mortality rate is about 2 per 100,000, as compared with 8 per 100,000 in the 1970s.
About 265,000 women die of cervical cancer annually, mostly in developing countries; around 700 women die of cervical cancer in the UK per year. Of those diagnosed today, over 60% will survive more than 10 years.
Full uptake of the vaccine is predicted by the Department of the Health to reduce this death rate from 700 to 300 per annum. These predictions were made prior to the publication of the Australian study in the BMJ. ANH-Intl is presently investigating whether the Department of Health will revise its predictions of benefit – and we will inform our readers of the outcome of our enquiries.
More about what’s really going on with adverse reactions
It is with adverse events that lies the greatest bone of contention. On our analysis, four important elements emerge that drastically change the risk/benefit balance as recounted by government agencies:
Firstly, available information from government sources is not made readily available to parents and children at the time consent is requested for HPV vaccination.
Secondly, the source data from which safety data are derived are “largely inadequate”, according to researchers at the University of British Columbia, being based on “selective reporting of results from clinical trials,… unproven assumptions (or such which are at odds with factual evidence) and significant misinterpretation of available data.”
Thirdly, despite the relative novelty of HPV vaccines, there is a rapidly accumulating body of evidence to show that the adverse event rate for this vaccine is considerably higher than for other vaccines, as shown by an analysis in The Independent newspaper published on 31 May 2015 and based on a freedom of information request.
Fourthly, based on multiple cases about which we have been made aware, the medical profession appears to be, by and large and with clear exceptions, poorly educated about how to respond to suspected adverse reactions to vaccines.
How serious are the adverse reactions to HPV vaccines?
One of the main sources of public information issued by the UK government is the MHRA’s post-market surveillance reports, the latest Public Assessment Report of which was published in December 2012. In essence, this report, if it were to be read by parents, would likely make parents feel that HPVvaccines are safe and effective or at least not more harmful than other vaccines.
Furthermore, the UK post-market surveillance applies primarily to four years of use of Cervarix and not the currently used Gardasil, which was only introduced in September 2012.
However, the freedom of information request by The Independent reveals a dramatically higher level of adverse events for HPV than any other vaccine, with 8,228 cases reported as a result of routine vaccinations between 1 January 2005 and 22 April 2015, as compared with 1,594 for the MMR vaccine, the vaccine with the next most commonly reported adverse events.
In the same article, the MHRA is quoted as accepting that these reports, as with any adverse reporting, probably estimate just 10% of actual adverse reactions. Recognition of the potential scale of the problem drove The Independent to issue its eye-catching headline, “Thousands of teenage girls enduring debilitating illnesses after routine school cancer vaccination” and suggest that “tens of thousands” of girls may suffer adverse reactions to HPV, some so serious they may lead to paralysis, long-term or potentially even permanent disability, as well as long-term conditions such as facial palsy, fibromyalgia and chronic fatigue syndrome.
These findings are entirely at odds with repeated statements by government and the MHRA that the safety profile is good and that adverse event rates for HPV vaccines are in line with other vaccines.
There are many instances, including that of Emily Ryalls detailed in The Independent, in which general practitioners (GPs) are highly dismissive about cases of reactions which develop shortly after vaccination. These cases of course do not provide causal evidence of a relationship, which is notoriously difficult to establish. It is unsurprising that Emily’s mother Carol has set up the Association for HPV Vaccine Injured Daughters (AHVID) that aims to bring together families with girls adversely affected by the HPV vaccine.
A day after the Emily Ryalls’ story was published in The Independent— after Carol had spent two years trying to interest journalists in her daughter’s case with no response until it was taken up by Paul Gallagher — the Daily Mail published a story detailing the case of 15-year-old Katie Green.
In its Public Assessment Report on 4 years of use of Cervarix, the MHRA indicates that upper respiratory tract infections and dizziness are “very common”, occurring at a frequency of about 1 in 10. The MHRA considers as common (1 in 100) effects such as anaphylaxis, angioedema, syncope (loss of consciousness) and fatigue, as well as Guillain-Barré syndrome, Bell’s/facial palsy, chronic fatigue syndrome/post viral fatigue syndrome, complex regional pain syndrome and encephalitis.
What’s happening in other countries?
Japan withdrew its recommendation for HPV vaccine in 2013 based on mounting public concerns about serious adverse reactions that include “serious cases of pains or body convulsions, pains in joints, or difficulty in walking".
Across the EU uptake rates were high in the initial states of the HPV vaccine’s introduction between 2006-8 in the European Union (EU). Uptake rates have now declined, a report by the European Centre for Disease Prevention and Control (EDPC) in 2012 stating, “One major issue, for some parents and healthcare professionals is the perception of the vaccine’s negative impact on the sexual conduct of adolescent girls.”
A Spanish study has found, in accordance with media reports, that neurological effects causing syncope and seizures was higher in adolescents exposed to the HPV vaccine than with other vaccines.
It’s a tough decision for anyone wanting the best for their daughter, and increasingly, their son, given that boys are now being targeted too for the HPV vaccine.
That decision is one that needs to be made when you're faced with your consent form. The most important thing to remember is, in the absence of complete and comparable information about risk and benefit, there is no right or wrong. Everyone simply wants to do the best by their child.
The commonly issued catch-cry of the likes of the MHRA is that the balance of benefit to risk is still positive. Well, risk and benefit assessment in such matters is never an easy judgment as you are effectively comparing apples and oranges. And what if the benefits are significantly lower, and the risks significantly greater, than is typically claimed by health authorities? With respect to the HPV vaccine, this is the very situation we believe we find ourselves in as a society. Given that most people don’t have adequate information on which to make a decision, how can truly informed consent be possible for most?
In a nutshell, and as discussed above, we can conclude that there is limited evidence of some effectiveness of the HPV vaccine, but this effectiveness is probably substantially lower than that which health authorities claim. Complicating the picture is that the government take on adverse events appears to understate the seriousness of adverse reactions.
We are blind to how far these reactions relate to the virus-like particles (VLPs) that comprise the key active ingredient in the vaccines, as compared with the adjuvants, which vary between vaccines.
As a society, what message are we giving to adolescent girls over HPV, which is essentially a sexually transmitted disease, if we continue to push for mass vaccination?
There are some clear steps that should be taken by parents and children choosing not to be exposed to the HPV vaccine.
The top three priorities should be:
Provide the necessary education so that young girls, prior to any sexual activity, understand the risks and mechanisms of HPV transmission by sexual activity, especially with multiple partners, including the fact that there is no risk without sexual activity and that risks can be significantly reduced through the correct use of condoms
Manage the health of the immune system by adopting a healthy, balanced and varied diet, plenty of regular exercise and appropriate stress transformation practices. More information can be found at Bite the Sun.
For women between 21 and 29 years of age, engage in cervical cancer screening by pap tests every 3 years until and assuming no negative cytological results, continue screening at 5 yearly intervals from the age of 30 - 65 or as recommended by your healthcare professional.