Sources include data from: National Cancer Institute, CDC, John Hopkins University, FDA, Merck Inc. and Co., GlaxoSmithKline (GSK), The American College of Obstetricians and Gynecologists, National Institutes of Health, Winship Cancer Institute, VAERS. Publications from: Current Pharmaceutical Design (2013), Discovery Medicine Journal (2010), American Journal of Public Health (2012), Pharmaceutical Regulatory Affairs (2012), Canadian Medical Association Journal (2003), Research and Reporting Methods (2010)
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“Your daughter could be one less.”[*]
An advertising campaign slogan seemingly designed to promote fear rather than actual evidence-based decision making about the potential benefits of the HPV vaccine.
When one takes a hard look at the scientific evidence, the more you may consider the sheer lunacy of the vaccine.
A Quick Recap
The What, Who, When and Where
The first HPV vaccine was added to the recommended routine childhood immunization schedule by the U.S. Centers for Disease Control and Prevention (CDC) in 2007.[*]
This vaccine is given as a series of three shots over 6 months - two vaccines (Cervarix and Gardasil) are currently approved and available for administration in the US.[*]
Out of 130 different types of HPV, nearly 30 are transmitted via sexual contact, 15 of which are oncogenic (may progress to tumor formation). Gardasil vaccinates against HPV types 6, 11, 16, and 18.[*]
HPV vaccination is recommended for all girls age 11 to 12, with "catch-up" doses for girls and women from 13 to 26 who haven't been vaccinated (there are no booster recommendation as of yet).[*]
Both vaccines are available for females. Only Gardasil is available for males (recommended ages 11-21).[*][*]
Let Thy Numbers Speak Clearly
Prevalence of Cervical Cancer
“Your daughter could be one less.” [*]
Of this entire post, the information in this section may be the most profound to the reader.
Based on data collected from 2008-2010 from Surveillance Epidemiology and End Results (published by the National Cancer Institute), there is a 0.66% chance your daughter will be diagnosed with cancer of the cervix at anytime during her life.[*]
Approximately 0.1% will be diagnosed under the age of 20.[*]
The median age at diagnosis for cancer of the cervix is 49.[*][*]
It is of extreme importance to recognize this point when reviewing this data:
2010 Discovery Medicine Journal
At this time, protection against cervical intraepithelial neoplasia grade 2/3 (CIN 2/3) is 5 years for Gardasil and 8.4 years for Cervarix.[*]
If your daughter receives an HPV vaccine at the recommended age of 11, protection will have waned by age 16.
The data collected from the above agency confirms approximately 0.0% deaths from cervical cancer under age 20.[*]
What is "one less" then 0%?
Pap Smears
The Saving Grace Against Cervical Cancer
Cervical cancer used to be the leading cause of cancer death for women in the United States. However, in the past 40 years the number of cases and deaths of cervical cancer have decreased significantly (as review in the previous section).[*][*]
This decline is attributed to regular Papanicolaou (Pap) tests, which has the ability to identify cervical precancerious cells before it turns into cancer.[*]
According to published data (2010 Discovery Medicine Journal), HPV vaccine efficacy must last at least 15 years to contribute to the prevention of cervical cancers. At the current time, protection against is at best 5-8 years.[*]
It is critical that parents and young women are given a full explanation of the importance of continued cervical screening and the real efficacy of the vaccine against cancer prior to administration.
Protection from Cancer
Real or Imaginary
The published data from clinical trials for both Gardasil and Cervarix appears to indicate 100% effectiveness against HPV-16 and HPV-18.[*][*]
That's pretty damn amazing.
However, you must understand that the conclusions of the HPV trials are based on clinical data extrapolated from a set of surrogate markers.
Now, this isn’t anything novel. Since disease progression is slow in the case of cervical cancer (20-40 years), it is more practical to use certain surrogate endpoints to measure a clinically meaningful outcome which will shorten the time required to complete the clinical trial.
However, these surrogate markers must be carefully assessed to maintain that they accurately measure what they are theoretically measuring - this is the essential piece in determining whether or not any meaningful clinical benefits can be expected from the HPV vaccine.[*]
The surrogate marker used in the clinical data to measure cervical cancer reduction was a reduction in cervical dysplasia (CIN1-3).
The money question:
A reduction in cervical dysplasia = HPV vaccine ability to reduce cervical cancer?
Cervical dysplasia refers is abnormal changes in the cells on the surface of the cervix that are seen underneath a microscope and are understood to hold the potential in progressing into cervical cancer (most often seen in women ages 25 – 35).[*][*]
Dysplasia is grouped into three progression categories:[*]
•CIN I -- mild dysplasia
•CIN II -- moderate to marked dysplasia
•CIN III -- severe dysplasia to carcinoma in situ
To answer our question, we will have to understand the progression and regression of HPV infection and Dyplasia.
HPV infection is common, occuring in 1 out of 5 women. 90% of HPV cases will resolve within 1-3 year without any intervention, less than 8% of HPV cases will screen positive for cervical dysplasia (CIN I – III).[*][*]
Of those women who do test positive for CIN I, a review of literature from 1950-1992 illustrates a 1% progression rate to invasive cancer due to the high frequency of natural regression in CIN I and CIN II. [*][*]
It is insurmountably clear that the surrogate markers used in the clinical data are insufficient in determining the true long term benefit of a prophalytic vaccine against cancer caused by HPV infection due to the benign nature and high frequency of regression of cervical dysplasia. [*][*]
In the natural course of cervical cancer, only a very small fraction of CIN I lesions will progress to CIN II and, from there, only a small fraction of CIN III will eventually progress to cervical cancer.
The incidence of HPV infection and the incidence of cervical cancer should not be considered equal since cervical cancer will not develop in most women who are infected even with high-risk HPV infections. [*]
The HPV vaccine to-date has not prevented a single case of cervical cancer, let alone cervical cancer death. Nor has the HPV vaccine improved the diagnosis of cervical cancer. [*]
"One less" of what? Clearly, not cervical cancer.
Safety
Is it Worth the Risk?
"Your daughter could be one more"
You may find yourself asking if it is even appropriate to risk any adverse effects to a preadolescent girl for a vaccine that is (1) only theoretically proven to prevent a disease that (2) she only has a 0.66% risk of developing over her lifetime – WHEN THE SAME CAN BE PREVENTED WITH REGULAR PAP SCREENING. [*][*][*]
Safety concern 1 - Exacerbate cervical disease
One poignant aspect to address regarding safety is the potential in the HPV vaccine to actually enhance cervical disease.[*][*]
If a young lady is sexually active prior to receiving Gardasil or Ceravix, it is possible that she may already be infected with the HPV. This is alarming due to rate of enhancement in cervical disease in the trial data.
Gardasil’s pre-licensure data observed an efficacy of -33 to -44.6% in women who were already exposed to HPVs targeted by the vaccine. [*][*]
An in a recent publication (2012 AJOG), high-risk HPV infection was diagnosed more frequently in vaccinated women than unvaccinated women (6.2% versus 2.6%).[*]
Safety concern 2 - VAERS
Another point worth addressing regarding safety is the adverse events reported after vaccination to various governments worldwide.
Wait, now - I fully recognize that a passive vaccine surveillance system does not prove causation between vaccine administration and an adverse reaction – However, since 2006, nearly 65% of all deaths and life-threatening reactions reported to VAERS from Gardasil or Cervarix alone. [*][*]
A total of 30,020 reports have been received by US VAERS including 2,574 hospitalizations, 9,114 ER visits 93 deaths.[*][*]
82% of cases resulting in permanent disability in females under 30 years of age was attributed to HPV vaccines. [*]
According to the FDA, thromboembolic events (blood clotting) are reported in a higher frequency from Gardasil then with other vaccines. Girls who are using oral contraceptives are at an increased risk, as well as those who are overweight and smoke.[*]
Other events included in HPV labeling: : local injection site reactions, syncope, dizziness, nausea, headaches, hypersensitivity reactions (such as rashes, hives, & itching), anaphylaxis, Guillain-Barré syndrome (GBS), transverse myelitis, motor neuron disease, pancreatitis, autoimmune disorders, and death. [*][*][*][*]
In contrast with the HPV vaccine, a pap test which uses a speculum to obtain cells from the cervix does not carry a risk of death, autoimmune complications or neurological dysfunction. And to the best of my knowledge, the procedure (LEEP) used to remove high-grade CIN II and CIN III lesions do not carry these risks either.
Safety concern 3 - AAHS Placebo Group
Currently, there are no regulations governing placebo composition, even though data gathered from placebo groups greatly influence trial safety outcomes, conclusions and policy recommendations for public use. [*]
The pre-licensure safety evaluation of Cervarix did not provide a saline solution control group to compare adverse outcomes.[*]
However, promisingly, the pre-licensure safety evaluation of Gardasil gathered data from 2 placebo groups: a saline solution group and an amorphous aluminum hydroxyphospate sulfate (AAHS) group. [*]
The aluminum-containing placebo group provided data on injection-site adverse reactions which resulted in 2-5 more ADRs then the saline placebo.[*]
However, in spite of the data gathered from injection-site ADRs, the manufacturer (Merck) pooled the results from the study participants who received the saline solution and the aluminum containing placebo to present as one ‘control’ group for systematic autoimmune disorders and serious reactions. [*]
The data reported in the package insert resulted in Gardasil having nearly the exact same rate of serious reactions as the “control” group (data of aluminum + saline combined). [*]
Clinical data that is inadequately designed cannot be used in a reliable manner to evaluate the safety of any drug.
The safety outcomes published for HPV vaccines with the use of an AAHS control group (versus a saline solution) produces false negative data and any meaningful conclusion becomes absent. [*]
The inadequate design of safety data is a reflection of the authority and influence the pharmaceutical industry maintains over the evaluation of its own products and publication its data. [*]
The Push for School Entry Mandate
Manufacturers influence on Policy
It may be appealing to consider that governmental policies involving vaccines are protected by the influence of private pharmaceutical manufacturers; however, there is a symbiotic relationship between the two.
However, this marriage is not inherently corrupt. Pharmaceutical companies provide informational resources and potential policy strategies to legislators and health department officials for many medical products, not just vaccines.
Nevertheless, the role that Merck & Co Inc played in legislation following the FDA 2006 approval of Gardasil seriously lacked appropriateness in vaccine policy.
The vaccine manufacturer aggressively engaged in direct lobbying, drafting specific legislation, presenting unrestricted grants - in most states, focusing on school mandates. One specific instance, Merck financially contributed to a national nonprofit group Women in Government (WIG) which pioneered a “legislative toolkit” containing model school-entry mandate legislation.[*]
The culmination of Merck’s direct lobbying was witnessed in Texas after Governor Perry issued an executive order mandating HPV vaccination for eligible preadolescent girls. The vaccine manufacturer quickly abandon engaging the issue once the public became aware of its role in contributed funds to the governor’s re-election campaign and that his chief-of-staff had worked for years as a lobbyist for Merck.[*]
It is best to acknowledge that vaccine manufacturer’s hold a unique place in policymaking. Government employees and legislators must be ever vigilant to identify that information presented may not be the same as a disinterested party – one that holds interest in selling a pharmaceutical product and securing a population that requires it.
Common Sense and HPV Vaccination
Conclusion
Parents making decisions about HPV vaccination on behalf of their young daughters must be fully informed of the real benefits against cancer when adding HPV vaccination to ongoing screening programs.[*]
To date, there is no data confirming HPV vaccines preventing or treating any cervical cancers. The large majority of HPV infection (and a great proportion of Cervical dysplasia) clear spontaneously without medical intervention, what indicates the surrogate markers in pre-licensure trials were an unreliable indicator of the number of cervical cancer cases that have been/will be prevented by the vaccine.
When reviewing the information on the HPV vaccine, I struggled to understand how parents (and girls old enough to consent themselves) are able to make a fully informed decision on whether to consent to Gardasil/Ceravix if critical information on safety and efficacy is not being presented to them.
I hope the information presented here facilitates a growing curiosity regarding HPV vaccination.
Disclaimer: The information contained on this blog is for educational and informational purposes only, and is not to be construed as medical advice. If you have any specific questions about HPV vaccination, HPV disease or cerivical cancers you should consult a professional healthcare provider. The decision regarding whether or not to vaccinate is a personal one.
Additional Information
Pap Test Recommendations[*]
New guidelines (released Dec 2012) from The American College of Obstetricians and Gynecologists (ACOG) state that most women need a Pap test every 3 to 5 years, rather than annually. However, if a woman is sexually active, they still recommend a yearly screening.
Scientists now know how HPV is transmitted, how few infected women develop cancer, and how slowly cancer develops. Because of the improved method of testing and collecting, new research and technology, the researchers are confident that getting regular, but less frequent, Pap tests is a safe option for women.
New Pap smear guidelines
• Pap smear tests should begin when a woman turns 21
• Women ages 21-29 should get screened every three years.
• Women age 30 and up can be screened every three years.
• After age 65 or 70, most women don't need a Pap smear test.
(Women who have certain risk factors and health issues, regardless of age, may need more frequent screening. This includes women who have HIV/AIDS, are immunosuppressed, were exposed to diethylstilbestrol (DES), or have been treated for cervical intraepithelial neoplasia (CIN) or cervical cancer.)
The value women place in HPV vaccines in conjunction with continued pap smear exams will be viewed differently by different women. Physicians' ethical duties are to provide full explanation of the risks and benefits of adding HPV vaccination to the ongoing screening programs, and to support women in their personal choice for cervical cancer prevention.[*]
Key Resources [*]
What Is HPV Infection?
Stories & Photos of Gardasil Vaccine Reactions
News on Gardasil Vaccine
· August 19, 2009. CBS News.Gardasil Researcher Speaks Out:“Public Should Receive More Complete Warnings.”
