University of British Columbia post-doctoral fellow and biochemist Dr. Lucija Tomljenovic reviews the data to determine the justification or lack of justification for immunization programs targeting human papilloma virus (HPV), which causes over 90% of cervical cancers. In doing so, Dr. Tomljenovic addresses two questions: What is the evidence that the HPV vaccine prevents cervical cancer and can therefore offer long-term clinical benefit? And what is the nature and incidence of HPV-related adverse events?
When considering vaccine effectiveness, one must consider the basis for a given vaccine’s use. The basis for HPV vaccination is its ability to prevent precancerous lesions related to HPV type 16 and 18 infections and the idea that preventing those lesions would prevent cervical cancer. According to University of Louisville researcher Dr. Diane Harper who led clinical trials of HPV vaccination, HPV infection can take years to result in cervical cancer. That leaves plenty of time for screening, treatment and prevention. Furthermore, 90% of HPV infections go away without treatment within three years. Only a tiny minority leads to cancer. Yet FDA licensed Merck's vaccine as a result of trials that were just three years long. Therefore, the long-term benefits of HPV vaccination concerning cancer prevention remain unclear.
A paper published in JAMA even asked how HPV vaccination in young girls is justified when it only partially prevents HPV infections – only a few of which will actually cause cancer, and not until 20-40 years after the initial infection. While Dr. Harper estimates that vaccine efficacy must hold for at least 15 years to prevent cervical cancer, GlaxoSmithKline's Cervarix vaccine is estimated to only last 8.4 years. Meanwhile, Merck's Gardasil vaccine is estimated to last just 4.5 years.
Overall, the annual incidence rate of cervical cancer in the developed world is very low. Just 8 in 100,000 develop cervical cancer each year in the United States thanks to cervical cancer screening. Yet simulation modeling operating under assumptions of 100% vaccination coverage and lifetime immunity predicts that the incidence rate would be 9.5 per 100,000 in the absence of screening with Cervarix and 14 per 100,000 with Gardasil. So even under these best-case scenarios, vaccination likely would not be more effective than screening at preventing cervical cancer. According to Dr. Tomljenovic, Dr. Harper does not expect combining vaccination and screening to significantly reduce cervical cancer cases.
Unfortunately, overconfidence in HPV vaccination has led to an impression that evaluation for effectiveness was unnecessary. Gardasil's European manufacturer has actually claimed that its vaccine provides 100% protection against cervical cancer. German regulators assumed lifelong protection in 92.5% of people vaccinated. As a consequence of the latter position, many physicians in Germany may have given the vaccine based on faulty assumptions.
Nonetheless, Dr. Tomljenovic stresses that PAP smear testing to screen for cervical cancer is not replaced by HPV vaccination as screening has reduced cancer mortality by 70% in the developed world. Effective or not, HPV vaccination would not further reduce cervical cancer mortality. On the contrary, if women who were vaccinated stopped being screened, incidence of cervical cancer would increase.
Research has suggested unimpressive HPV vaccine efficacy. One recent study from Canada yielded numbers in teenage girls that showed vaccine effectiveness at a mere 20-35% among 15 to 17 year olds for various cervical cancer lesions. Overall, there was little difference in probability of developing precancerous lesions over a three year period in vaccinated vs. unvaccinated cohorts.
Nonetheless, false advertising from Merck, the American Academy of Pediatrics and US Centers for Disease Control have included claims that Gardasil is the only vaccine against cervical cancer, that Gardasil is a “life-saving vaccine” and that it can potentially benefit millions of American women. All these claims are either untrue or ill-founded based on the current evidence.
Although the evidence does not support HPV vaccination’s effectiveness in the developed world that does not mean vaccination could be useful in the developing world. In India for example, PAP smear screening is not widespread and cervical cancer is more of an issue. The reality is that secular trends of cervical cancer in India have been on a steady decline without mass vaccination. In one paper published in a Southeast Asian journal cited by Dr. Tomljenovic, the authors stressed that cervical cancer’s multi-factorial nature suggests that vaccination would not necessarily be effective at reducing cancer. They also noted that the lack of an effective screening program does not justify mass vaccination and recommended that public health policy be independent and not dictated by those with ties to vaccine makers who have much to gain from mass vaccination programs.
Merck's aggressive marketing of Gardasil is largely done to offset losses incurred by other drugs that have been proven to be either unsafe or less effective than thought, and the firm has done so with some success. In Canada for example, Merck has been successful at expanding the market for Gardasil by having the vaccine also approved for use in young adult women.
Such aggressive marketing may not be without serious health consequences for patients. In 2012, Dr. Tomljenovic published a paper in the American Journal of Public Health with colleague Dr. Christopher Shaw. They analyzed the Vaccine Adverse Events Reporting System (VAERS) managed by FDA and CDC, and they found that Gardasil was associated with some 60-65% of serious, life-threatening or fatal adverse events reported to the database and 81.2% of permanent disabilities. Some 17 autoimmune events were associated with Gardasil, of which 5 including fibromyalgia appeared most strongly correlated.
In another published paper, Drs. Tomljenovic and Shaw also found that reported adverse events following HPV vaccination were most commonly associated with neurological and psychiatric conditions across the UK, Ireland and the Netherlands. Japanese scientists also found the same to be true for HPV vaccine adverse events reported in Japan.
Yet the European Medicines Agency (EMA) dismisses such events as “psychogenic” and unrelated to the vaccine, though EMA is horribly conflicted. The majority of the members of the EMA panel evaluating the vaccine's safety accepted contributions from vaccine manufacturers in approving and promoting HPV vaccination. So biased are some of the European advisors overseeing vaccination policy, that one even called for doctors questioning the safety of HPV vaccination “to be stopped” and for money to be spent to diminish the prominence of vaccine skeptic websites in Google searches and boost those promoting the vaccine. European parliament and the prestigious Cochrane Institute have further raised concerns about the objectivity of these regulators, even questioning the legality their conflicts of interest pose.
In closing, Dr. Tomljenovic challenges her audience with a question: Is it ethical to put at risk of death or a disabling autoimmune disease at a pre-adolescent age for a vaccine that has not yet prevented a single case of cervical cancer, a disease that may develop 20-30 years after exposure to HPV, when the same can be prevented with regular PAP screening which carries no risks? Probably not.
However, that does not necessarily mean vaccines should never have a place in preventing cervical cancer. Quoting a clinician from Denmark who treats patients who suffered adverse health effects following HPV vaccination, Dr. Tomljenovic suggests the answer to the problems that come with mass vaccination and genetic susceptibility to vaccine side-effects may be “personalized vaccines.” These would be vaccines developed with the appreciation of individual differences in immune response to vaccination and how that triggers both effects and side-effects. This would challenge the current paradigm of “one-size-fits-all” mass vaccination programs, done on the basis of protecting people with “herd immunity.” Nonetheless, denial of the safety and efficacy problems posed by HPV vaccination is no solution to those problems.