TV commercials plug it, the FDA approved it, news highlights tout it, but there are serious concerns about the new vaccine Gardasil® from Merck. Medical Accountability Network Executive Director Dr. Moira Dolan has reviewed the information made generally available to physicians and outlines here the essential components of informed consent for what is being billed as a miracle anti-cancer vaccine.
Telling the truth about the new vaccine Gardasil – Does it prevent cancer?
A guide to informed consent
by Moira Terese Dolan, M.D.
© Medical Ethics, Inc.
The prevention of genital warts and cervical cancer is an extremely worthwhile effort. However, like any drug, the vaccine is not a cure-all and it has some potential downsides. There is an urgent need for full informed consent for potential human papillomavirus (HPV) vaccination. It is the role of the administering physician to remind the parent or patient that FDA approval does not equate to safety. The FDA also turns a deaf ear to the fantastically misleading direct-to-consumer advertising claims. It is the duty of the physician to sort through the hype and government approval and official pronouncements, to provide full informed consent to each and every patient. The essential components of informed consent are:
- what the drug (vaccine) is,
- what is known and not known about how well it works,
- what is known and not known about safety,
- alternatives to the vaccine,
- the consequences of choosing to take or not take the vaccine.
Gardasil® vaccine is Merck’s first big drug development since the Vioxx® disaster. The basis for many Vioxx® lawsuits is that Merck withheld information that clearly showed the dangers of the drug. The company’s record does not inspire trust.
The Vioxx® situation revealed a more treacherous problem existing within the FDA itself. FDA insiders exposed how the agency deliberately ignored abundant test information showing that Vioxx® was dangerous to cardiac patients. The systemic failure of the FDA to weigh the risks and protect the public without undue influence of the manufacturers was brought to light by Vioxx® but it has not yet led to any meaningful changes at the agency. In spite of thousands of Vioxx® product liability suits still unresolved, Gardasil® has gotten fast track FDA approval, soon to be followed by Glaxo’s Cervarix®.
What is Human Papillomavirus disease?
The HPV infection that is under discussion is a virus that is transmitted by skin to skin or genital to genital contact during sexual activity. It commonly causes genital warts, although infection may occur completely out of view on the cervix, where it is not apparent and does not show any symptoms. There are some 150 named HPV types. Newer testing methods that detect the DNA sequence of viruses demonstrate that there is actually a lot more variation in viral types than this 150, with some suggesting that there are thousands of distinct viral types.
What is the Merck HPV vaccine?
The Merck vaccine contains recombinant-generated Virus Like Particles from four strains of human papillomavirus (HPV), numbered 6, 11, 16 and 18. It is approved for females age 9 to 26. It is given in 3 doses over 6 months, at a drug cost of $360.
Condom use dramatically reduces chance of infection from all types of HP viruses, by as much as 70%. There is no specific anti-viral treatment for infection, but the majority of infections are cleared by the immune system anyway. Of women who contract HPV infection, 90% will clear the infection through the body’s natural immune processes. The younger the patient the more rapidly they naturally clear infection.
What is cervical cancer?
Cervical cancer is cancerous growth on the lower portion of the womb, the part that extends into the vagina. Between 1955 and 1992, the number of cervical cancer deaths in the United States dropped by 74%. The death rate continues to go down by about 4% per year. Half of the cases of cervical cancer occur between the ages of 35 and 45. It is rare under age 20. U.S. statistics show 3-4 cervical cancer cases per year per 100,000 women age 9-26. These are the ages on which the new vaccine was tested.
The American Cancer Society reports that cervical cancer is responsible for about 1% of cancer deaths per year. Some claim that this low number is due to effectiveness of routine Pap screening, which results in the detection and treatment of pre-cancerous lesions so that they never get to the cancer stage. However the big drop in cervical cancer also coincides with an increased use of condoms, so it is more likely a combination of the two factors. Nutritional deficiencies, especially vitamin A and folate, mineral deficiency (zinc, selenium, calcium and iron), smoking, birth control use and douching have been shown to be associated with cervical cancer. Increase in number of sex partners is a major risk factor for cervical cancer. HPV infection is highly associated with cervical cancer, yet there remains debate as to whether the virus actually causes cancer.
The vast majority of abnormal Pap tests do not equate to cancer. Even abnormal Pap tests showing pre-cancerous cells of the CIN II grade clear by themselves with no treatment 40% of the time. Treatment of pre-cancers has limited the progression to cancer to only 1%. So Merck’s vaccine is coming out at a time when cervical cancer is already on the decline. This is similar to the polio vaccine, which came out when polio was already rapidly going away on its own.
How is HPV infection related to cervical cancer?
30 types of HPV have been found in association with cervical cancer. HPV type 16 is currently found in 50% of cases of cervical cancer, and type 18 is found in 20% of cases of cervical cancer. Some cervical cancers don’t have associated HPV, and most people infected with HPV do not get cancer, so HPV cannot be the full cause of cancer. Some researchers and FDA scientists wonder if the abnormal cells (cancerous or pre-cancerous) may simply be a friendly environment for viruses to grow around, so the virus infection may occur after the changes that cause cancer rather than the other way around. Smoking has more to do with the progression of HPV infection to cervical cancer than any other single factor. Smokers with HPV go on to develop cervical cancer much more frequently than infected non-smokers.
Does the vaccine work? Who studied the vaccine in humans?
It is a crucial part of full informed consent to let patients know that all human studies submitted to the FDA were done by or financed by the drug manufacturers. It cannot be brushed aside that these studies have limited to no independent scientific review. In fact, it takes a formal Freedom Of Information Act request to obtain the exact study reports and statistical analyses that the drug manufacturer gave to the FDA.
What is the effect of the vaccine on HPV infection?
In the general population the Merck vaccine prevented genital warts that were due to vaccine-type strains. The vaccine prevented human papillomavirus infection with four HPV subtypes in people who weren’t already infected with these types. The vaccine did not prevent infection with the HPV types that are not contained in the vaccine.
HPV disease due to one of the many subtypes NOT included in the vaccine still occurred. Vaccinated subjects got infected with non-vaccine HPV types at the same rate as non-vaccinated subjects.
In subjects who were already infected with a particular vaccine virus type, the vaccine did not prevent disease due to that type, but it did prevent new disease caused by the other vaccine subtypes.
The studies that the drug maker gave to the FDA did not tell if condom use was tracked; this is very important missing data, since condoms alone are responsible for a 70% reduction in all types of HPV. The vaccine gives 100% protection against four HPV types and no protection against other HPV types, whereas condoms give 70% protection against all HPV types.
What is the effect of the vaccine on cervical cancer?
Since HPV is found in connection with most cervical cancers, the theory was that a vaccine against HPV would prevent cervical cancer. However the vaccine studies couldn’t demonstrate this, simply because there were no cases of cervical cancer in the vaccinated group or in the group that got dummy shots. So they used a substitute measure (a ‘surrogate marker’) for cancer. They compared abnormal pre-cancerous Pap results in people who were vaccinated versus not vaccinated.
The vaccine is nearly 100% effective in preventing four types of HPV infection. Two of the four subtypes included in the vaccine are currently responsible for 70% of cervical cancer. So we would expect a 70% reduction in precancerous Pap results, right? However pre-cancerous Paps only went down by 12% to 45%, depending on which population was studied. (See below for the different populations and the reasons for this spread.)
Why didn’t the vaccine cause a 70% reduction in pre-cancers in the general population?
This could be explained by some method of viral shift. Since the vaccine HPV types got pretty much wiped out as being a cause of pre-cancers SOMETHING must have taken their place because pre-cancers only reduced by 12.2% to 16.5%. The alternate explanation (raised by an FDA scientist) is that the theory that ‘HPV causes cancer’ could be backwards. Maybe HPV is just a so-called ‘opportunistic infection’ that is allowed to flourish un-checked in the vicinity of cancer cells.
U.S. statistics show there are 30 to 40 cervical cancer cases per year per one million women age 9-26, the ages the vaccine was tested on. Gardasil®’s reduction of pre-cancers by 12.2% to 16.5% in the general population would mean that instead of 30 to 40 cases of cancer, there would only be 26 – 35 cancers. So it would take vaccination of a million girls to prevent cancer in 4 to 5 girls. About 37% die from cervical cancer, so that would prevent 1 to 2 deaths. So $360 million in vaccine would prevent 1 to 2 deaths.
However this is all conjecture. In the Merck studies the follow up was too short and the numbers too few to prove prevention of cervical cancer.
Results vary in different populations
The vaccine studies were analyzed in several different ways. One analysis looked only at girls whose pre-vaccine testing did not show any evidence of current or past infection with the HPV types that are in the vaccine. In people who did not already have one of the four types of HPV, the vaccine was 91 – 100% effective in preventing pre-cancers that were associated with the four vaccine HPV types. They still got pre-cancer associated with non-vaccine HPV types at the same rate as un-vaccinated girls.
The only way to know if you are going to get this response is if you have never had sex before the vaccine, or you have been tested for evidence of prior infection. The HPV test is recommended by the American Cancer Society as part of cancer screening every three years in women older than 30, but it is not yet widely covered by insurance plans outside of these recommendations.
The more useful analysis was called “the general population”. This is all study participants analyzed together, without separating out the ones who had tests showing current or prior infection with vaccine-type HPV. The results for the general population are much different. Because most women are not getting pre-vaccine HPV tests, these numbers apply to all but virgins. In the general population there was little over 12% reduction in pre-cancer associated with any type of HPV.
Is the HPV vaccine safe? Can the HPV vaccine actually make infection worse?
The study showed an increase in pre-cancer related to the vaccine types in the people who already had these infections before they got the vaccine. It is possible that when infected girls whose immune systems have not cleared the virus from their bodies are vaccinated, the vaccine may lead to an increased number of cases of a pre-cancer. This is very concerning, because there is no routine test you can get in your doctor’s office that will tell if you are already infected by a vaccine type HPV before you get the vaccine.
How does the HPV vaccine affect fertility? Birth defects? Risk of cancers? Breast milk?
Five subjects who got the Merck vaccine around the time of conception had babies with birth defects, whereas no birth defects occurred in this time period in the subjects who got dummy shots. The manufacturer also specifies that the vaccine has not been tested to see whether it could cause cancer. It is not known if the vaccine virus-like proteins or the antibodies pass into the breast milk. Merck says that it should not be given to pregnant women.
The longest portion of the study only lasted just under four years. Thus there is no long term data on how it affects the ability to become pregnant (fertility). This is especially concerning because the FDA has approved the vaccine for as young as 9 year old girls. The effect of artificially influencing the immune system during a time of tremendous hormone shifts of puberty is unknown.The package insert specifies that the vaccine has not been tested for altering genes in the patient or her future children (genotoxicity).
Comparison to other vaccines
Hepatitis B vaccine was rushed to the market and broadly administered to young people in the absence of adequate human safety testing. It is now one of the most common vaccines reported to the Vaccine Adverse Effect Reporting System, particularly for gastrointestinal problems, arthritis and multiple sclerosis. The new HPV vaccine uses aluminum and polysorbate, two substances known to cause cancer in laboratory animals and to alter immune responses.
What are the consequences of declining the vaccine?
The ultimate prevention of HPV is abstinence. Condom use is at least 70% effective in preventing all types of genital HPV infection. HPV infection is often eliminated by the body’s natural immune mechanisms. Abnormal Pap tests often return to normal on their own. Cervical cancer is on the decline as are cervical cancer deaths, but it still occurs in about 10,000 women a year with 3,700 dying.Pap tests are required whether or not you take the vaccine. (see the VRAN website for Canadian stats)
Who would benefit from the vaccine?
If you have risk factors for HPV infection such as multiple sex partners and no condom use, and you are not already infected by one or more of the subtypes targeted by the vaccine, this vaccine protects you from HPV infection by the four subtypes, but not non-vaccine HPV types.
If you have cervical cancer risk factors such as nutritional deficiencies, multiple sex partners or smoking, the vaccine prevents some episodes of growth of pre-cancerous cells and it may prevent cancer. The vaccine is 12.2% to 16.5% effective in the general population in reducing pre-cancer Pap results. The vaccine is 45% effective over the short term in girls who have never had any of the vaccine-type HPV infections.
The long term safety and effectiveness of Gardasil® is unknown. Effects on causing cancer, infertility, gene mutations, birth defects and effects in breast milk have not been adequately studied in humans.
Batieha,et al, Cancer Epidemiol Biomarkers Prev, 1993
Cunzhi, et al, Biol Trace Elem Res, 2003
Geier and Geier. Annals of Pharmacotherapy, 2002 March; 36, pp. 370-374
Gunnell, et al, Cancer Epidemiol Biomarkers Prev, 2006 Nov;15(11):2141-7
National Vaccine Program Office, Workshop on Aluminum, May 2000.
Winer, et al, NEJM June 22, 2006, Vol 354:Number 25: 2645-2654
We appreciate Dr. Dolan’s kind permission for allowing us to reprint this article. For additional web references go to: http://www.medicalaccountability.net This article is no longer accessible on the Medical Accountability website.