For shame! Annals of Medicine publishes hit piece on HPV vaccine
When I first saw this paper prairiedogging around anti-vax websites, I just rolled my eyes and figured it had been published in another one of the faux journals out there that looks legit but is really not peer-reviewed and has an impact factor hovering somewhere around absolute zero. But once I got a few moments, I checked out the reference and discovered that the steaming turd of a paper to be discussed in today’s blog was, shamefully, published in Annals of Medicine. I confess that I haven’t read many articles in this journal before, but its alleged impact factor of 5.4 indicates that apparently quite a few other people are reading it. It’s not Lancet-caliber, but it’s a mid-ranked journal and not a total fishwrap…at least not usually.
Papers like this sometimes make me wish that articles, when published, included the names of the reviewers and the editor who nannied the paper through the review process. Because I cannot imagine who reviewed this paper, found it legitimate, and recommended publication. The editorial board of Annals of Medicine should be thoroughly embarrassed.
The paper in question is entitled “Human papillomavirus (HPV) vaccine policy and evidence-based medicine: Are they at odds?” (1).
The paper kicks off with a bolded header entitled, “Can the currently licensed HPV vaccines prevent cervical cancer?”
The authors admit that HPV vaccines Gardasil and Cervarix are, in fact, extremely effective at preventing HPV 16 and 18 infections and pre-cancerous cervical lesions, also known as cervical intraepithelial neoplasia (CIN). They then go on to imply that the companies that make the vaccines are trying to pull the wool over our eyes by stating that the “testing period employed was too short to evaluate long-term benefits of HPV vaccination.” Well, yeah. As the authors themselves acknowledge, it takes 20-40 years for cervical cancer to develop. The vaccine itself is less than a decade old in terms of gathering data. So how on earth can ANYONE have attained an adequate sample size for examining the actual cervical cancer endpoint? Answer: they can’t have. It’s simply impossible. More disturbing however is the authors’ apparent belief that the HPV-to-CIN-to cancer pathway is hogwash. Because the only way they can insinuate that HPV vaccine won’t prevent cervcial cancer is to ignore this well-understood and well-established pathway to cervical carcinogenesis. If HPV vaccine prevents CIN, then it WILL prevent cervical cancer. But Tomljenovic and Shaw? Pshaw! It appears from the wording in this section that they do not seem to believe the scientific data of the last 50 years regarding HPV causing cervical cancer. But let’s continue. The next bolded section header is:
Gardasil and Cervarix: do the benefits of vaccination outweigh the risks?
Again the authors begin by banging on the idea tha HPV vaccine has not been proven to work. Again, this is simply because of the time it takes for cervical cancer to develop, not because of some conspiracy. They then go on to indicate that the risk of serious adverse events from Gardasil is “2.5 times higher” than the risk of death from cervical cancer in the United States. There are several serious reasoning flaws with this approach. The first is that the authors use the Vaccine Adverse Event Reporting System (VAERS) as their source for adverse event reporting. VAERS is an excellent system in terms of brute-force data collection. However, this system allows for anyone and everyone to report ANYTHING that has happened to them after they received HPV vaccine, from falling down a flight of stairs to bruising at the injection site. The major problem is that these reports may have nothing whatsoever to do with the actual vaccination.
Here is a thought experiment. Imagine that we have the MAERS (milk adverse event reporting system). Everyone has access to the system and can report any adverse event that occurs after drinking milk. We’re going to see reports of odd white moustaches, flatulence, diarrhea, diabetes, myocardial infarction, and autism. Are these things caused by drinking milk or are they coincident to the fact that a large proportion of Americans drink milk every day? You can see the problem here, reader, and if you like you can read more about the problems of interpreting VAERS in the blog post linked below, by Karen Ernst at Moms Who Vax (2). The problem for Tomljenovic and Shaw is that the CDC has studied these VAERS reports in detail and has observed no unusual clustering of ANY serious adverse events after HPV vaccine. Thus, the entire “analysis” comparing serious adverse events to cervical cancer deaths collapses in on itself, no matter how much hand-waving about VAERS reports is included. Further, the authors utterly ignore the other sequelae of HPV, such as biopsies, cryo-treatments, and massive anxiety, as I have discussed here previously (3). The next major header is:
Side-effects from HPV vaccines: are they a minor concern?
Here again we have a lot of hand-waving and insinuations. The authors begin to bang away on one of the adjuvants in the vaccine, ASO4, with such lines as, “All of the eight authors of the ASO4 safety study are employees of GlaxoSmithKline (GSK), the manufacturer of Cervarix”. It is very interesting that Tomljenovic and Shaw are attempting to cast aspersions about a study based on the funding source…but more on that below. Anyway, the authors ignore other peer-reviewed studies of ASO4 done by independent laboratories (4), as well as that the fact that ASO4 is a somewhat new adjuvant, the development of which would by rights be first reported on by the lab that created it. Regardless, the two authors provide no data whatsoever that this specific adjuvant might be dangerous; rather, they rail at the fact that there are not enough data showing its safety in individuals with autoimmune disorders. Why they are now wandering down the road of autoimmune disease is unclear, though they make some further insinuations that vaccines might “trigger” autoimmune diseases, cherry-picking the literature and ignoring the copious amounts of data showing the general safety of vaccines in individuals with autoimmune disorders.
They state, for example, that multiple sclerosis is a “serious demylenating disease of the central nervous system that typically follow(s) a febrile infection or vaccination”. The latter part of this statement is beyond ridiculous, as it is akin to stating that these diseases typically follow the inhalation of air. In fact, some vaccines, including tetanus and diptheria, are actually significantly associated with a consistent and substantial reduction in risk for multiple sclerosis (5), but this is not discussed. They then go on to list and beat on every disorder ever reported to VAERS, despite that fact that the CDC has detected no clustering of any disease after HPV vacccination. But just ignore that, Tomljenovic and Shaw, in your blindered quest to make your point.
Next up, we have: Safety assessment of HPV vaccines in clinical trials: was it adequate?
Tomljenovic and Shaw lead off with a trite analysis of placebos and of what they should be made. They then start hammering on the fact that the clinical trials of HPV vaccine used a placebo that contained aluminum adjuvant. The idea is that Merck and GSK were manipulating the trials such that any adverse events caused by the vaccine would be matched by including aluminum in the placebo, and as such both the test and placebo arms would have equivalent, but artificially so, rates of adverse events. Oddly, they later go on to admit that many of the trials used separate saline placebo and aluminum placebo arms. So how on earth could they have been manipulating the placebo group to make the drug look more favorable?
In addition, Tomljenovic and Shaw, a basic tenet of the placebo-controlled trial is that the placebo is IDENTICAL to the active drug, with one difference–the lack of the component being tested for efficacy, which in this case would be the HPV virus-like particle (VLP). Let’s say that the test drug included the aluminum adjuvant and the VLP, while the placebo did not contain the adjuvant. When, in 20 years, the vaccine has been shown to have substantially reduced the risk of cervical, anal, and head and neck cancers, there would be tinfoil hatters that would claim that it was the ALUMINUM that prevented cervical cancer, not the VLP. And there would be no data to indicate otherwise. Therefore, the placebo MUST contain the adjuvant for a fair test of the actual drug.
Are HPV vaccines cost-effective?
I’m not a health economist, though I’ve worked on grants in this field. I can tell you that it’s an extremely difficult area of study and it requires major expertise to conduct a cost-benefit analysis with any reliability at all. If my reader wants to comment on this section, that would be great. It seems to me that the authors make a heck of a lot of assumptions for this analysis, though, and I’m not at all sure of its accuracy.
Are there safe and effective alternatives to HPV vaccination?
The authors start this section off with this quote:
Although approximately 275,000 women die annually from cervical cancer worldwide, almost 88% of these deaths occur in developing countries.
Right. Developing countries. Areas where women are in many cases marginalized, and where there may be rampant poverty and a severe lack of regular access to healthcare. You know what may work better than a Pap Smear in these areas? A vaccination, that’s what. The authors blather on and on about how the Pap is superior to the HPV vaccine, which may be true in a perfect world where every woman can get a Pap each year. But we don’t live in a perfect world. Or maybe we just shouldn’t care about HPV in women who cannot afford or who do not have access to a clinic to run in and get a Pap every single year (or every three years, as the case may be).
How does HPV vaccine marketing and promotion line up with international ethical guidelines for informed consent?
This section is a bit odd because it begins with an attempted assassination of the FDA. Okay, agreed-the FDA has some problems. But anyway, they go on and on talking about the advertising blitz that Merck did for Gardasil. Agreed, Tomljenovic and Shaw, Merck was largely responsible for the backlash against its own drug by promoting it so heavily. But if you are seriously going to look at the ethics in drug advertising, you’re going to need to go a lot deeper than the HPV vaccine, a drug that has been proven to be safe and effective. Given that Shaw is heavily involved in developing his own drug (6), I’m not certain he wants to go too far down that road. There are other serious flaws with their argument, including what appears to me to be a fundamental misunderstanding of who is responsible for informed consent, but perhaps I’ll tackle that at another time.
I doubt that the authors see the irony here. But buried in the last paragraph is this statement: “The presentation of partial and non-factual information regarding cervical cancer risks and the usefulness of HPV vaccines, as cited above, is, in our view, neither scientific nor ethical.”
That’s right, Tomljenovic and Shaw. In my view, your paper is neither scientific nor ethical. The Editors of Annals of Medicine, the reviewers who approved this piece of crap paper, and the editor who ushered it to publication should hang their heads in shame. Perhaps the anti-vaccination activist groups who funded the authors feel differently, however, especially since at least one of these authors has taken their dog-and-pony show out on the anti-vax lecture circuit (7), a very lucrative area indeed.
If you are interested in more information on who provided the funding for this paper, the Dwoskin Foundation was the major supporter of a National Vaccine Information Center (NVIC) conference (8). NVIC is an established anti-vaccination activist organization. The Katlyn Fox Foundation provides a veritable cornucopia of anti-vaccination propaganda (9). The authors reported these conflicts of interest, and the impact of the funding source on the product can only be guessed at.
(1) Tomljenovic and Shaw, Annals of Medicine, December 22 2011. For now this is in early online form, but here is the link: http://informahealthcare.com/doi/abs/10.3109/07853890.2011.645353
(7) This work was supported by the Dwoskin, Lotus and Katlyn Fox Family Foundations. L.T. and C.A.S. conducted a histological analysis of autopsy brain samples from a Gardasil-suspected death case. C.A.S. is a founder and shareholder of Neurodyn Corporation, Inc. The company investigates early-state neurological disease mechanisms and biomarkers. This work and any views expressed within it are solely those of the authors and not of any affiliated bodies or organizations. A portion of this information was presented at the Vaccine Safety Conference, 3 – 8 January 2011 (www.vaccinesafetyconference.com).