Posted by David Gorski on March 7, 2016 It’s amazing how, to antivaccine activists, it just so happens that a vaccine that targets a sexually transmitted virus must also destroy a girl’s ovaries. It must be a coincidence, right? When you’ve been blogging for over 11 years on your own blog and 8 years on a blog like Science-Based Medicine, particularly when what you blog about is skepticism and science-based medicine, with a special emphasis on rationally and scientifically discussing quackery, inevitably you see the same misinformation and lies pop up again and again. Indeed, those of us in the…

It's amazing how, to antivaccine activists, it just so happens that a vaccine that targets a sexually transmitted virus must also destroy a girl's ovaries.

It’s amazing how, to antivaccine activists, it just so happens that a vaccine that targets a sexually transmitted virus must also destroy a girl’s ovaries. It must be a coincidence, right?

When you’ve been blogging for over 11 years on your own blog and 8 years on a blog like Science-Based Medicine, particularly when what you blog about is skepticism and science-based medicine, with a special emphasis on rationally and scientifically discussing quackery, inevitably you see the same misinformation and lies pop up again and again. Indeed, those of us in the biz not infrequently refer to such stories as “zombie lies,” because no matter how often you think they’ve been killed they always come back. Personally, I like to refer to them as Jason, Michael Myers, or Freddy Krueger lies (or just slasher or monster lies), for basically the same reason. You kill them with facts, evidence, science, and reason, but sooner or later they always come back. Always. That’s why trying to refute them is like playing Whac-A-Mole. This time around, a group called the American College of Pediatrics (ACP) is claiming that Gardasil is causing infertility in girls, a claim that showed up last week on that repository of quackery, Oddly enough, despite the article’s hysterical tone, it wasn’t written by NN’s big macher himself, Mike Adams.

The reason that slasher lies keep coming back is because they never really go away completely. They only look that way because they recede for a while until someone new discovers them or their originators decide the coast is clear and they can repeat them again. There’s one particular slasher lie that keeps coming up about the HPV vaccine, usually Gardasil (mainly because that’s the brand of HPV vaccine most commonly used in the US) but not restricted to Gardasil. Sometimes Cervarix falls prey to the same lies, mainly overseas where it is the predominant version of HPV vaccine used. Given that I was in Boston at the annual meeting of the Society of Surgical Oncology over the weekend and was also busy hanging out with Kimball Atwood and Clay Jones one night, surgical colleagues another night, and the Boston Skeptics on Saturday, it seemed to me to be a good time to revisit this topic, particularly given that it hasn’t been covered on SBM before. If this post looks familiar, it’s because it has appeared before, but it was in a different form. Consider this a beefed up version of the prior post, because even when I recycle material I can’t just recycle it unchanged. I have to tinker, add, and, of course, customize for the blog. It’s what I do.

The slasher lie returns

The slasher lie I’m referring to is, of course, the claim that the HPV vaccine causes infertility and sterility in adolescent girls and young women. Actually, it’s not entirely true that this is an antivaccine claim unique to the HPV vaccine. After all, it wasn’t so long ago that I discussed a pernicious lie being spread by Catholic bishops in Kenya claiming that it had been spiked with beta-hCG as a means of birth control. Another time, the same culprits claimed that the polio vaccine was being spiked with estrogen in order to sterilize Kenyan girls. Both claims were, of course, ridiculous, but the idea is there: Someone is using vaccines for “population control,” and they’re doing it by rendering young girls sterile. Actually, this is a very common conspiracy theory among the antivaccine faithful, that “someone” (usually involving Bill Gates) is using vaccines to depopulate the world.

So what makes the conspiracy theories about Gardasil different? Simple. Antivaccinationists have a special hatred for Gardasil. I realize that it sometimes annoys some of our readers when one of us waxes political or ideological, but in this case it really can’t be avoided. The hatred and fear of Gardasil and Cervarix very much appear to derive from the fact that HPV vaccines are used to prevent a sexually-transmitted virus, the rationale for that fear being that the use of such a vaccine will somehow “encourage promiscuity.” It’s even been called the “promiscuity vaccine.” Never mind that the evidence is quite clear that this claim is simply not true. Never mind that anyone who remembers her own adolescence clearly would know that fear of catching HPV and then developing cervical cancer 20 or 30 years down the road is not a major concern among teens as their raging hormones drive their behavior. None of this matters to the people making these claims, however, who seem to think that cervical cancer is a just punishment for “promiscuity” and naturally seem to latch onto conspiracy theories in which HPV vaccines would naturally cause infertility because the “promiscuous” shouldn’t be mothers.

Perhaps the link with sex and the fact that it is designed to combat a sexually-transmitted virus are what make the most pernicious slasher lie about Gardasil, that it causes primary ovarian insufficiency, more commonly known as premature ovarian failure (POF), so hard to kill for good. Basically, POF is early menopause and usually defined as loss of normal ovarian function before the age of 40. It can and does occur in young women and even teenagers, for whom it is a particularly devastating problem. (Just imagine going through, in essence, menopause at age 15 and you’ll get an idea of how profoundly horrific POF can be.) The linking of a vaccine viewed as promoting promiscuity to a punishment of losing fertility is simply too natural and irresistible to cranks, regardless of how wrong it is. Not surprisingly, this is exactly what we see in the aforementioned article, which is based on a press release by the American College of Pediatrics entitled “New Concerns about the Human Papillomavirus Vaccine.” You can tell you’re in for a heaping helping of BS from the very first paragraph:

The American College of Pediatricians (The College) is committed to the health and well-being of children, including prevention of disease by vaccines. It has recently come to the attention of the College that one of the recommended vaccines could possibly be associated with the very rare but serious condition of premature ovarian failure (POF), also known as premature menopause. There have been two case report series (3 cases each) published since 2013 in which post-menarcheal adolescent girls developed laboratory documented POF within weeks to several years of receiving Gardasil, a four-strain human papillomavirus vaccine (HPV4).1,2 Adverse events that occur after vaccines are frequently not caused by the vaccine and there has not been a noticeable rise in POF cases in the last 9 years since HPV4 vaccine has been widely used.

It’s rather amusing that the authors note that there hasn’t been an increase in POF incidence since the introduction of Gardasil, but nonetheless strain mightily to blame POF on the vaccine. Given the number of girls vaccinated over the last decade, if Gardasil were linked to POF we’d expect to have found evidence in the various vaccine safety surveillance systems in place to find adverse reactions to vaccines. That no such link has been found is suggestive, albeit admittedly not conclusive, that there probably isn’t a link.

Gardasil and premature ovarian failure: Slaying the slasher lie

To analyze what the ACP has said thus far, let’s take a look at the two references cited. Reference 2 can be dispensed with fairly easily. The first case discussed in the reference, for instance, was one of the first dubious testimonials claiming to link POF with Gardasil that I’ve ever encountered. It’s no more convincing in the article cited than it was in the BMJ Case Reports article from which it originated. Basically, the argument (as is the case the case with nearly all of these stories) is that because no other cause for this patient’s POF could be determined upon investigation, it must have been the Gardasil.

Of course, the vast majority of cases of POF are idiopathic; i.e., no clear cause is ever found. (Of the remainder, the cause is usually rare chromosomal abnormalities, autoimmune diseases, and other rare disorders.) It’s frustrating, but true. It’s also true that POF is more common than most realize; as many as 1 in 100 girls and women suffer from it.

You can see this problem in the second case, which is that of a woman who was diagnosed with POF at age 18. She received her series of three doses of HPV vaccine at 12 years and 9 months; near her 13th birthday; and at age 13 years and 5 months. That’s right. The author of this paper, Deirdre Therese Little, blamed POF occuring nearly five years after the patient’s last dose of Gardasil on the vaccine. To explain this long delay between vaccine and discovery of POF, she noted that the young woman had been on oral contraceptives since age 12 for irregular menstrual periods, which were stopped briefly at age 14 with a three month period of amenorrhea, and then restarted. She also had several health problems, including cerebral palsy, asthma, epilepsy. Overall, Little was clearly reaching very far to blame this case of POF on Gardasil. I hope she didn’t hurt her back or shoulder.

The third case is the only one that showed a reasonable temporal correlation, with the patient’s first late period occurring after the third dose of the HPV vaccine, but even that correlation is pretty thin gruel, as it is correlation without convincing evidence of causation. As is the case for vaccines and autism, is it not surprising that there are girls and young women who suffer POF in close temporal relation to their having received a dose of Gardasil. In fact, what surprises me more than the ability of antivaccine activists to find cases of girls whose onset of POF can be related to their having received a Gardasil booster, however tenuous and forced the correlation might be, is just how few cases they can find: Around six in the entire developed world, if you believe the statement, and of these at least half do not even have a correlation between vaccination and symptom onset convincing enough even to suspect that this correlation might equal causation. Add to this just how hard these activists are looking for such cases, and, even given how uncommon POF is before the age of 18, it’s actually rather amazing that Little and her fellow anti-Gardasil activists haven’t flooded the case report literature with such cases. Instead, we have about a half dozen.

Ultimately, Little even had to admit at the end of the article that case reports “do not and cannot establish causation,” but she certainly tried her best to spin every cherry picked preclinical study she can find to implicate Gardasil in these girls’ POF. She even goes so far as to cite dubious studies claimed to show that polsorbate 80 in vaccines can cause infertility in rats as well as the bogus claim that detection of HPV DNA in the vaccine is a great danger, which is a bit of misinformation promoted by pathologist Sin Hang Lee. It also turns out that Dr. Little is on the board of advisors for an Australian Catholic anti-abortion group called Family Life International, whose official patron laments the growth of promiscuity and the “redefining” of marriage (big surprise, the group is against gay marriage as well). On the website is a diatribe against Gardasil, which, FLI gravely notes, is “often associated with promiscuity,” along with a link to a YouTube video of the antivaccine propaganda film The Greater Good. It also turns out that Little’s co-author, Harvey Rodrick Grenville Ward, is cut from the same cloth, described as a “pro-life obstetrician/gynecologist.” He also apparently helps an antiabortion activist named Stephanie Gray give talks at local churches in Canada in which she shows graphic abortion videos to convince the audience that abortion is “wrong 100% of the time.”

Also not surprisingly, Reference 1 is an article by Lucija Tomljenovic and Yehuda Shoenfeld that claims that the HPV vaccine can trigger an autoimmune syndrome, part of whose manifestation is premature ovarian failure. These two are antivaccinationists we’ve met before. Shoenfeld is best known for having made up a syndrome that he calls ASIA (“Autoimmune/Inflammatory Syndrome Induced by Adjuvants”) for which no compelling evidence exists. He’s also known for having provided pseudoscientific reports to bolster antivaccine claims that vaccines cause autoimmune disease and being the scientific advisor for The Greater Good. Speaking of The Greater Good, Tomljenovic is known for working closely with Christopher Shaw, an antivaccine scientist who appeared in the film to proclaim that we’re all living in a “toxic” soup and that vaccines are part of that soup. Basically, they both publish lots of articles claiming that the aluminum adjuvants in vaccines (particularly Gardasil) are causing horrific health problems; they’ve even blamed Gardasil incorrectly for a death, as was reported by The Toronto Star in one of the worst mainstream news articles I’ve ever seen on Gardasil. Yes, working with other antivaccine scientists, Shaw and Tomljenovic have tried to show that Gardasil kills. It doesn’t.

The first case presented is a 14 year old girl who suffered amenorrhea after her series of HPV vaccine doses. The second is a case of a girl who was vaccinated with HPV at age 13, which was before she had her first period at age 15, when she had only two periods separated by one month. (Yes, they blame Gardasil doses given before this girl’s onset of menses for POF that happened two years after the doses.) The third case is a 21 year old woman who developed irregular menses after her third dose of HPV vaccine and ultimately became amenorrheic at age 23. Based on this thin gruel, Lucija Tomljenovic and Yehuda Shoenfeld conclude, “In this case, as in our three cases, no other possible causes of POF were identified other than the HPV vaccine.”

In other words, even though in the vast majority of cases of POF no specific cause for ovarian failure can be identified, to Tomljenovic and Shoenfeld that must mean it was the Gardasil that done it! They claim it’s because the vaccine can cause an autoimmune syndrome like ASIA, even though they present no clinical evidence that any of these patients had an autoimmune syndrome. It’s the classic tendency of antivaccine activists to confuse correlation with causation.

Of course, this isn’t the first time Tomljenovic and Shoenfeld have worked together. In fact, I’ve even encountered them quite recently, when they tried (and failed miserably) to show that Gardasil causes behavioral problems in mice.

Gardasil: When the slasher lie is down, don’t take your eyes off of it

As you can see, the evidence presented by the ACP as warranting concern about the ability of Gardasil to cause POF both comes from highly biased sources and rests on some pretty tenuous “correlations.” None of this stops the ACP from claiming:

Nevertheless there are legitimate concerns that should be addressed: (1) long-term ovarian function was not assessed in either the original rat safety studies3,4 or in the human vaccine trials, (2) most primary care physicians are probably unaware of a possible association between HPV4 and POF and may not consider reporting POF cases or prolonged amenorrhea (missing menstrual periods) to the Vaccine Adverse Event Reporting System (VAERS), (3) potential mechanisms of action have been postulated based on autoimmune associations with the aluminum adjuvant used and previously documented ovarian toxicity in rats from another component, polysorbate 80,2 and (4) since licensure of Gardasil® in 2006, there have been about 213 VAERS reports (per the publicly available CDC WONDER VAERS database) involving amenorrhea, POF or premature menopause, 88% of which have been associated with Gardasil®.5 The two-strain HPV2, CervarixTM, was licensed late in 2009 and accounts for 4.7% of VAERS amenorrhea reports since 2006, and 8.5% of those reports from February 2010 through May 2015. This compares to the pre-HPV vaccine period from 1990 to 2006 during which no cases of POF or premature menopause and 32 cases of amenorrhea were reported to VAERS.

Of course, as has been described before many times, the VAERS database is not a useful tool for assessing incidence or changes in incidence of adverse reactions due to vaccines. The reason is simple. Anyone can submit reports of adverse events to VAERS. Anyone. The reports undergo minimal or no vetting by medical professionals. Heck, there is even a famous description of how a man successfully submitted a report that a vaccine turned him into The Incredible Hulk. What that means is that any belief about a vaccine’s adverse effects can lead to more reports being filed. Worse, we’ve known for at least a decade that vaccine litigation itself distorts the database. Indeed, it’s very likely that the publicity of a “link” between Gardasil and amenorrhea or POF is the very reason why the vast majority of reports to VAERS of amenorrhea or POF are associated with Gardasil and why such reports took off after Gardasil and Cervarix were licensed. Basically, none of the above claims is compelling evidence that Gardasil or Cervarix is associated with POF.

Nor is this:

Few other vaccines besides Gardasil® that are administered in adolescence contain polysorbate 80. Pre-licensure safety trials for Gardasil® used placebo that contained polysorbate 80 as well as aluminum adjuvant. Therefore, if such ingredients could cause ovarian dysfunction, an increase in amenorrhea probably would not have been detected in the placebo controlled trials. Furthermore, a large number of girls in the original trials were taking hormonal contraceptives which can mask ovarian dysfunction including amenorrhea and ovarian failure. Thus a causal relationship between human papillomavirus vaccines (if not Gardasil® specifically) and ovarian dysfunction cannot be ruled out at this time.

I can’t help but note that the rat studies mentioned early in the statement used massive doses of polysorbate 80, far beyond what is in any vaccine; so their relevance to, well, anything is highly questionable. Basically, at best ACP has a few case reports, some of which aren’t even particularly convincing as single case examples of correlation, much less as evidence of causation, plus some cherry picked animal research. There are also appeals to ignorance. For instance, Scott S. Field, MD, the author of this statement, notes a very large study that found no evidence of a link between Gardasil and demyelinating or autoimmune diseases but dismissed it not having looked specifically at POF. So basically, based on some tenuous correlations, some reports in VAERS, and irrelevant science, Field recommends trying to scare primary care doctors to scare parents about Gardasil.

The American College of Pediatrics: Not the American Academy of Pediatrics!

The large number of bad arguments in its statement led me to ask: Who is the ACP, after all? On the surface, it sure sounds like a professional organization for pediatricians, such as the American Academy of Pediatrics (AAP). Wrong. The ACP does little resembling what a professional society does; certainly it doesn’t offer continuing medical education credit. Certainly it is not the “leading association of pediatricians” in the nation, as its advocates claim. In fact, here’s the origin of the ACP:

In February 2003, the American Academy of Pediatrics (AAP) issued a policy statement declaring its support for homosexual parenting. The statement urges the states to extend the status of legal parent to same-sex partners, as well as marriage-equivalent status to homosexual and lesbian couples.

However, a new group–the American College of Pediatrics, a Tennessee-based alternative organization headed by Dr. Joseph Zanga–has just responded by requesting that its fellow organization reverse its stand.

Zanga’s group was formed by 100 dissenting members of the AAP. His organization disagrees with the AAP’s point of view on gay parenting, as well as numerous other social issues.

That’s right, the ACP is a small splinter group of conservative pediatricians who broke away from the AAP over its support for parenting by homosexual couples 13 years ago:

“We are essentially a Judeo-Christian, traditional-values organization,” he noted, “open to membership for pediatric medical professionals of all religions who hold to our core beliefs.” Those beliefs, he said, are that “life begins at conception, and that the traditional family unit, headed by an opposite-sex couple, poses far fewer risk factors in the adoption and raising of children.”

The chief purpose of his organization, Zanga commented, is to see to it that children and adolescents receive optimal healthcare, with children’s needs coming first, taking precedence over the political aims of socio-political activists.

And here’s how the ACP describes its values:

The American College of Pediatricians:

A. Recognizes that there are absolutes and scientific truths that transcend relative social considerations of the day.

B. Recognizes that good medical science cannot exist in a moral vacuum and pledges to promote such science.

C. Recognizes the fundamental mother-father family unit, within the context of marriage, to be the optimal setting for the development and nurturing of children and pledges to promote this unit.

D. Recognizes the unique value of every human life from the time of conception to natural death and pledges to promote research and clinical practice that provides for the healthiest outcome of the child from conception to adulthood.

E. Recognizes the essential role parents play in encouraging and correcting the child and pledges to protect and promote this role.

F. Recognizes the physical and emotional benefits of sexual abstinence until marriage and pledges to promote this behavior as the ideal for adolescence.

You get the idea. The ACP is anti-gay marriage, anti-abortion, and promotes the pseudoscience that claims that abstinence-only education is an effective means of reducing the incidence of teen pregnancy. Basically, it’s a phony medical group peddling anti-gay propaganda and pseudoscience to schools.

Unsurprisingly, the ACP now appears to have latched on to anti-Gardasil antivaccine pseudoscience as well. Quelle surprise.

HPV vaccines are effective and safe

Unfortunately, the ACP’s tactic has been more effective than I would like. The original article on the crank website Truthkings trumpeted the ACP statement as “Pediatricians Association Admits HPV Vaccine Causes Ovarian Failure“, making it sound as though a real, legitimate academic pediatrics association had concluded that there is something to worry about. It rapidly went viral with sites like The Healthy Home Economist and Collective Evolution. Because the ACP’s name sounds very official and academic, not surprisingly, the theme that pediatricians were “admitting” that Gardasil can cause premature ovarian failure was very attractive, and many were the articles in the “alternative medicine” and antivaccine blogosphere and on crank websites portraying this as the admission of a coverup. Fortunately, the ACP’s statement was so bad that even at last one who would be inclined to agree with the group on an ideological basis mercilessly eviscerated the ACP’s misinformation.

The bottom line is, as Steve Novella has summarized, the HPV vaccine is effective and quite safe. As a recent review described it:

A number of examinations of the VAERS data for HPV vaccination have shown a low rate of adverse reactions, and no link for any causal relationship between HPV vaccination and reports [43, 44]. There are a variety of conditions that can occur in the absence of HPV or other vaccinations, in young adolescent females, which can be mistaken for HPV vaccination side-effects, and therefore to draw conclusions from adverse event data to HPV vaccination is to mistake (time) correlation for causality [45]. In 2009 Slade and colleagues [44] investigated the 32 deaths attributed to Gardasil® that had been reported on VAERS. Of the 32 deaths there was not enough information to identify or verify the death for 12 reports. The causes of the remaining 20 deaths were: 2 due to diabetic ketoacidosis, 3 due to pulmonary embolism, 6 were cardiac-related (4 arrhythmias, 2 myocarditis), 2 were idiopathic seizure disorders, 4 were unexplained, 1 was due to juvenile amyotrophic lateral sclerosis, 1 case of Neisseria meningitidis serogroup B caused meningoencephalitis and the final death was related to prescription drug abuse. The authors concluded that statistically (proportional reporting ratio of 1.2 for 8- to 29-year olds) these results were not significantly (p=0.92) different from what you would expect from a similar sized unvaccinated population.

In marked contrast, let’s see what a real pediatrics association (the American Academy of Pediatrics) says about Gardasil:

Clinical trials have revealed the vaccine to be highly immunogenic, safe, and well tolerated in males and females 9 through 26 years of age. Antibody responses are at least twice as high in individuals of both genders 9 through 15 years of age as in those 16 through 26 years of age. HPV4 was licensed for use in females in 2006; antibodies have been shown to persist for at least 9 years. HPV4 was licensed for use in males in 2009; the duration of vaccine-induced antibodies is still under investigation but is known to be at least 5 years.

Science, man. It works. It produces wonderful things like vaccines that can prevent cancer.

While discussing (and dismissing on scientific grounds) the claimed link between Gardasil and POF in a recent editorial, “Human papillomavirus vaccination and primary ovarian insufficiency: an association based on ideology rather than evidence“, David Hawkes and Jim Buttery noted a problem that applies to claims of adverse events after all vaccines:

Little and Ward complained that adverse events following immunization were not recorded beyond 7 months after vaccination. However, they provide no rationale or biological mechanism for including a longer interval between HPV vaccination and onset of POI [premature ovarian insufficiency], other than suggesting adolescent girls may not associate a decline or loss of fertility with vaccination if it occurs slowly over time. As the time between HPV vaccination and the first symptoms of POI increases it becomes more difficult to draw a conclusion of causation, particularly in the absence of a biological mechanism. Little and Ward provide no maximum time period between vaccination and the onset of symptoms beyond which they would consider an association unlikely, and with some claiming a causational relationship even with a 15-year interval between vaccination and symptoms [7], a defined temporal criterion is essential.

Which illustrates a more general problem:

Without a plausible biological mechanism we are reliant upon epidemiological studies to refute claims such as these. To conduct such studies, an agreed case definition of POI is required, with initial identification of cases occurring without knowledge of vaccination status or timing. So in essence the claim of an extremely rare reaction to HPV vaccination that results in a poorly defined, uncommon condition is virtually impossible to refute rapidly, and may take years of international collaborative study.

This is exactly the problem with many claims of adverse events after vaccination. Antivaccine advocates won’t be pinned down, and trying to get them to admit a time frame after which they would agree that an association with vaccination is unlikely is like trying to nail jello to a wall. The same, not coincidentally, is true with their claim that vaccines cause autism. Even if a child’s first symptoms of autism develop many weeks or months later, it still must be the vaccines that did it!

Unfortunately, this particular slasher lie that Gardasil renders girls infertile by causing premature ovarian failure is certainly not dead. As always, there will be a sequel, and as usual it won’t be as good as the original movie, which was bad enough to begin with. The bottom line is that Gardasil is effective and very safe, and much of the opposition to it, especially claims that it damages female fertility, is rooted in ideology, not science.

Posted in: Public Health, Religion, Vaccines

Source: The claim that Gardasil causes premature ovarian failure: Ideology, not science : Science Based Medicine