Antivaccinationists against the HPV vaccine, Round 5,000

Whenever I take a day off from blogging, as I did yesterday because I was too busy going out with my wife on Wednesday night to celebrate my birthday, I not infrequently find an embarrassment of riches to blog about the next day. Sometimes it’s downright difficult to decide what to write about. So it was as I sat down last night to do a bit of blogging. I briefly considered writing about Suzanne Somers leaping into the fray to defend Stanislaw Burzynski, and maybe I still will. On the other hand, it’s standard boilerplate Burzynski apologetics, not even very interesting; so maybe I won’t. There were others, including a news story about something going on in my very own home town, which I’ll probably wait on until next week. Then I was made aware by some Facebook friends of an anti-Gardasil “study” going around the antivaccine crankosphere right now that claims that Gardasil induces ovarian failure and infertility, and I knew I had to perform yet another public service combatting bad studies promoting antivaccine pseudoscience.

The last time I dealt with this topic was last fall, when a highly dubious case report of a 16 year old girl who developed ovarian failure. Of course, to the antivaccinationists it just had to be Gardasil. It just had to be. Because vaccines. It almost certainly wasn’t, but that didn’t stop the antivaccine contingent from flogging the case report as being slam dunk evidence for a link between the HPV vaccine and premature ovarian failure. Unfortunately, antivaccinationists are still flogging this study. It even showed up earlier this week on as a “newly published study” even though it was published last October. As “evidence” that the HPV vaccine causes premature ovarian failure, this case report was thin gruel indeed. The girl didn’t start to have irregular menses until five months after her last dose of Gardasil and didn’t stop menstruating altogether until nearly a year later.

This next “study,” by Serena Colafrancesco and investigators at the Zabludowicz Center for Autoimmune Diseases Sheba Medical Center, Tel-Hashomer, Israel and the Rheumatology Unit, Department of Internal Medicine and Medical Specialities, Sapienza University of Rome, Rome, Italy and entitled Human Papilloma Virus Vaccine and Primary Ovarian Failure: Another Facet of the Autoimmune/Inflammatory Syndrome Induced by Adjuvants is just more of the same. Instead of one weak case study, we have three weak case studies put together to make a case series. As we say in the biz, the plural of “anecdote” is not “data,” and this paper is a perfect example of this. Moreover, one of our favorite new antivaccine “researchers” is involved in this paper, a veritable “rising star” of the antivaccine movement, Lucija Tomljenovic. When last we saw her, she was twisting and distorting other case reports to make it look as though Gardasil was responsible for two deaths when it almost certainly wasn’t. In fact, when I see Tomljenovic’s name on a paper, I know that the relationship between the reported findings (which will always claim that vaccines cause horrible consequences) and reality will be related only by coincidence, if even that.

Let’s look at the cases. I’ll briefly comment on each one and then comment on all three of them together in the more lengthy, detailed way that you know and love.

Here’s case #1:

A young previously healthy girl received three administrations of the quadrivalent HPV vaccine (T0, T1 after 4 months, T2 after 9 months) when she was 14 years old. Six months before the first injection, the patient had menarche. Her psycho-physical and sexual development were normal except that at the time she received the first HPV vaccine dose, she was complaining of irregular periods (every 2 months). After the first vaccination, the patient immediately started to complain of burning and heavy sensation in the injected arm, followed by skin rash and fever. Nausea and stomach aches lasted for 2 days after the injection, while in the subsequent 2 weeks, she further complained of cramping and headache. At the time of the second vaccine administration, she reported similar injection site related symptoms, accompanied by sleep disturbances, such as insomnia and night sweats. At the time of the third injection, the patient continued to experience the same symptoms: burning, pain and heavy sensation in the injected arm, headache and cramping. Insomnia associated with night sweats persisted and she started complaining of arthralgia, anxiety and depression. The patient reported that her last period occurred shortly after the last injection of the HPV vaccine. The hormonal screening showed the presence of increased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) associated with very low levels of estradiol. Beta human chorionic gonadotropin (HCG) tested negative excluding pregnancy. The karyotype study was 46 XX, while molecular studies ruled out Fragile X syndrome and mutated follicle-stimulating hormone receptor (FSHR) gene. A pelvic ultrasound did not show any abnormality. According to these clinical and serological findings, POF diagnosis was determined. Even though the patient started therapy with medroxyprogesterone to stimulate bleeding, no improvement occurred and she continued to experience abnormal vaginal bleeding, night sweats, hot flashes and sleep disturbances.

Note that at the time this patient received her first dose in the three dose series of Gardasil she was already complaining of irregular periods. This strongly suggests that, whatever was going on to cause her difficulties was going on when she started her first dose of Gardasil. Overall, this is pretty thin gruel. So let’s look at the second case:

This patient (the younger sister of the above-mentioned case) received three administrations of the quadrivalent HPV vaccine at the age of 13 under the same protocol as her sister. At that time, she had normal growth and sexual development. The patient complained, 10 days after the first injection, of general symptoms such as depression and sleep disturbances. She also experienced episodes of lightheadedness and tremulousness, anxiety, panic attacks and difficulties in focusing/concentrating in her school work. She had menarche at the age of 15 years, followed by another period 1 month later and none thereafter. Laboratory analysis showed high serum levels of FSH and LH with undetectable estradiol. The genetic test for Turner’s syndrome, Fragile X syndrome and FSHR gene was performed and resulted negative. Interestingly, the patient tested positive for antiovarian antibodies. She underwent a pelvic ultrasound without an evidence of abnormalities. In the light of these findings, a diagnosis of POF was determined and the patient was treated with several different hormonal replacement therapies with a poor therapeutic response.

There are multiple interesting things about this case. First, this is the sister of the girl who was case #1. Now, I don’t know about you, but if I were to see two examples of premature ovarian failure (POF) in two sisters, I’d wonder if there were some sort of genetic predisposition. There is, after all, a variant of POF that is familial. That the most common genetic cause was ruled out doesn’t mean that there can’t be others. As I’ve pointed out before, the vast majority of causes of ovarian failure before the age of 40 are idiopathic, and we don’t know all the potential genetic causes. The second thing about this case that stands out is that she had her series of Gardasil injections at age 13 and then had menarche (the onset of menstruation, for you non-medical types out there) at the late end of the normal range of ages for menarche. She only had two periods, though, and then no more. This was roughly two years later, but it had to be the Gardasil that caused it! In other words, this case is, if anything, even less convincing than the first case.

So let’s see if the third case is any more convincing:

The patient received the quadrivalent HPV vaccine in three administrations (T0, T1 after 2 months, T2 after 4 months) at the age of 21 years. Menarche occurred when she was 13 years old with normal monthly periods and a flow of 5–7 days, with mild cramps. A normal sexual development was reported. Few months after the last injection of HPV vaccine, she started complaining of irregular menses (off by 1–2 weeks) without an increase in bleeding or pain. The irregular periods worsened and the patient reported on menstruations every 3 months with bleeding only for 2 days. For this reason, she started drospirenone/ethinyl estradiol. Nonetheless, no improvement occurred and after discontinuation of therapy, at the age of 23 years, she complained of amenorrhoea. The laboratory tests showed the presence of very low levels of estradiol and increased FSH and LH. Testosterone, cortisol and prolactin serum level were found normal. Although the thyroid hormones were also in the normal range, the patients had positive antithyroid peroxidise (TPO) antibodies (134 IU/mL, n.v. 0–34). The karyotype evaluation and the search for Fragile X syndrome displayed no aberrations. A transvaginal and pelvic ultrasound did not reveal any abnormality. According to these findings and clinical features, a diagnosis of POF was determined. Thus, a therapy with medroxyprogesterone and estradiol was attempted, however, it did not improve her clinical condition.

Here we go again. It’s the same thing. Problems with menstruation occur a “few months” after the last injection of Gardasil and continued a couple of years before amenorrhoea occurred.

So what we have are three females, two of them teens and one of them a young woman, with primary ovarian failure. All of them have the key elements of POF, namely amenorrhea, low estrogen levels, and high gonadotropin (FSH and LH) levels. Its incidence is generally around one in a thousand before the age of 30. That’s rare, but not so rare that it’s really hard to find cases.

So how do the authors link these three cases, the first two of which look like familial idiopathic POF and the last of which looks like simple idiopathic POF? They invoke an entity called ASIA (Autoimmune/Inflammatory Syndrome Induced by Adjuvants). From what I’ve been able to tell, ASIA is basically a made-up syndrome that isn’t generally accepted. The authors of this article describe it as group of diseases that include “post-vaccination phenomena,” silicone implant–induced autoimmunity, Gulf War syndrome, macrophagic myofasciitis with chronic fatigue syndrome, and the sick-building syndrome. Note that all of these, with the exception of chronic fatigue syndrome, are highly dubious entities whose existence as distinct clinical syndromes is questionable at best. Even more dubious are the clinical criteria, four major and four minor, that are used to “diagnose” ASIA. The idea is that either two major criteria or one major and two minor criteria are required for a diagnosis of ASIA. Out of curiosity, I went back to what appears to be the original article in which ASIA was defined by Yehuda Shoenfeld, who is known for testifying for “vaccine injury” victims and running a journal sympathetic to antivaccine views, even publishing works by quacks like Mark and David Geier. The “syndrome” appears to have been made up of whole cloth based on unfounded assumptions. He’s also been known to speak at antivaccine conferences and “vetted” the antivaccine propaganda movie The Greater Good for “accuracy,” and the movie’s producer promotes ASIA.

If you look at how ASIA is defined, it’s so vague that almost any immune abnormality can be so classified, as long as somewhere, somehow, the patient had exposure to an adjuvant, in this case in the form of the adjuvant used in Gardasil, which is amorphous aluminum hydroxyphosphate sulfate), and that’s just how these authors do it. No evidence is presented, and they labor mightily to turn three anecdotes into “data.” Basically, their “reasoning” (such as it is) boils down to this. Three females developed POF sometime within several months to a couple of years of receiving Gardasil. Two of them had autoantibodies, but not the same autoantibodies. Therefore, Gardasil must have caused their ovarian failure through ASIA. Yes, their arguments are just that bad.

There’s almost no limit to the ridiculousness to which antivaccinationists will descend to attack Gardasil. A favorite tactic is to link it with infertility and POF. Why that particular entity? I think I know. Gardasil protects against a sexually transmitted disease, HPV. So giving Gardasil lets sluts have sex. So there must be consequences related to sex, and those consequences are infertility. I could be wrong, but aks yourself: Why the obsession with infertility related to Gardasil in the absence of any even remotely compelling evidence?