One more time: There’s no evidence Gardasil causes premature ovarian failure

Here we go again.

When you’ve been blogging for over 11 years, particularly when what you blog about is skepticism and science-based medicine, with a special emphasis on taking down quackery (particularly cancer and antivaccine quackery), inevitably you see the same misinformation and lies pop up from time to time. 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 yesterday on that repository of quackery,

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. 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.

Perhaps the most distinctive lie about Gardasil and Cervarix is that it causes infertility and sterility in girls. Actually, that’s not entirely true. 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. 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. That hatred seems to be based on the fact that HPV vaccines are used to prevent a sexually-transmitted virus, the rationale somehow being that the use of such a vaccine will “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 their 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 hormones rage. None of this matters to the people making these claims, however.

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 does sometimes 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 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 blame POF on Gardasil. 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 not conclusive, that there probably isn’t a link.

Before we go on, let’s take a look at the two references cited. Reference 2 can be dispensed with fairly easily, because I discussed at least one case in it in detail when it was published. The first case discussed in the reference, for instance, was one of the first dubious testimonials claiming to link POF with Gardasil that I 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 it the case with most of these stories) is that because no other cause for POF could be found upon investigation, it must have been the Gardasil. Of course, most cases of POF are idiopathic; i.e., no clear cause is ever found. It’s frustrating, but true. The second case was that of a woman who was diagnosed with POF at age 18, while 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. POF occuring nearly five years later was blamed on the HPV vaccine. It was noted that she 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. 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 is pretty thin gruel.

Ultimately, the author, Deirdre Therese Little, even had to admit at the end of the article that case reports “do not and cannot establish causation,” but she certainly tries 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. The first case 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 suffered by one month. 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! It’s the classic tendency of antivaccine activists to confuse correlation with causation. Of course, we’ve met Tomljenovic and Shoenfeld before, quite recently in fact, when they tried (and failed miserably) to show that Gardasil causes behavioral problems in mice. Earlier, working with antivaccine scientist Christopher Shaw, Tomljenovic has tried to show that Gardasil kills.

Oh, and they’re both big into trying to “prove” that aluminum adjuvants in vaccines cause autism. Meanwhile Shoenfeld made up a syndrome called ASIA (“Autoimmune/Inflammatory Syndrome Induced by Adjuvants”) for which no compelling evidence exists.

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 I’ve described before, 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. So 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.

First off, those rat studies mentioned early in the statement used massive doses of polysorbate 80 to affect ovarian function; 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 and 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. Of course, POF is, fortunately, a relatively uncommon condition, particularly in teenagers, and there really isn’t much in the way of compelling evidence to suggest a link. Certainly there is not enough in the way of evidence to justify Field’s last recommendation, which is that “primary care providers be notified of a possible association between HPV and amenorrhea.” No, there isn’t really any compelling evidence upon which to base such a recommendation.

But who is the ACP, after all. 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 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. Surprise, surprise.