Guard Against Gardasil

By Elissa Mendenhall
Issue 142 - May/June 2007

In September 2006, the State of Michigan approved two measures to require girls entering the sixth grade to be vaccinated with Gardasil, the new vaccine for human papillomavirus (HPV). Touted as the "anti-cancer vaccine," Gardasil is widely hailed in the public health community as a giant step toward preventing cervical cancer. After four clinical trials, the FDA approved its use in June 2006, and Gardasil is now available by prescription.

Clinical trials have found that Gardasil is nearly 100 percent effective in preventing certain strains of HPV infection—a tremendous feat in the world of vaccine research. There is no doubt that the introduction of Gardasil has dramatically altered the public-health landscape for both sexually transmitted infections and cervical cancer. But are we ready to make the leap from a handful of promising clinical trials to mandating vaccination for all preadolescent girls?

HPV and Cancer

Humans and HPV have an interesting and complex relationship. HPV is best known for causing common warts and cervical cancer, but there are more than 100 different strains of HPV. Because of the cancer link, the strains that are of the greatest medical concern are those that are sexually transmitted. These strains can cause genital warts, or can be associated with cervical and other cancers of the genital area. Approximately 13 percent of American women are infected with genital HPV.¹ Infection with the HPV virus is an important cofactor in cervical cancer, but very few people infected with HPV will ever get cervical cancer. At least 80 percent of women will have acquired a genital HPV infection by the time they are 50 years old, and about 6.2 million American men and women get a new genital HPV infection each year, according to estimates by the Centers for Disease Control.² Compare this to the national rate of cervical cancer. In 2003, the National Cancer Institute estimated the number of cases of cervical cancer at 253,781.³ In 2002, 4,000 women died from the disease in the US.⁴ While this is a sizable number, it represents a tiny fraction of those infected with the virus. HPV infection is asymptomatic in most people. Until recently, most cases went undetected.

With recent advances in detection of the HPV virus, it appears that the norm is more one of infection than of disease. In most cases, the virus's relationship with its host is symbiotic: It causes no harm and is not easily detected. "Although HPV is a necessary cause of cervical cancer, it is not a sufficient cause. Thus, other cofactors are necessary for progression from cervical HPV infection to cancer,"⁵ states Nubia Muñoz in a recent article in the medical journal Vaccine. Saying that HPV causes cervical cancer is similar to saying that being of African descent causes sickle-cell anemia: It is an oversimplification that fails to look at other factors. For instance, the World Health Organization notes that up to 30 percent of cervical cancer deaths in the US are attributable to smoking cigarettes.⁶

The Two HPV Vaccines

Two HPV vaccines are currently available or in the works: Gardasil, produced by Merck & Co. and already approved by the FDA; and Cervarix, produced by GlaxoSmithKlein, still awaiting FDA approval. Gardasil is a quadrivalent vaccine; that is, it contains four strains of HPV: the two most associated with cervical cancer, and the two most associated with genital warts. The bivalent Cervarix contains the two strains of HPV most associated with cervical cancer. Neither vaccine contains mercury in the form of the preservative thimerosal, but both contain aluminum hydroxide, which acts as an adjuvant—an agent that helps stimulate the needed immune reaction.

There is some concern that aluminum can cause long-term problems. The metal can collect in the brain, and is associated with Alzheimer's disease. It is also linked to defective mineralization and osteomalacia.⁷ Aluminum is generally well tolerated in the small quantity that is in the vaccine, but its long-term effects as a vaccine additive have not been well established.

The FDA approved Gardasil in what the agency calls its "priority review process,"⁸ which takes six months or less, and is used for medications with the "potential to provide significant health benefits." The available published research on Gardasil, however, was primarily from sources that were not objective. The two studies that were published and available for review were funded entirely by the manufacturer.^9,10 The other studies are not available for review, but were presumably conducted by the manufacturer in its own laboratories.

Cervarix has complications of its own. In addition to aluminum, it contains a new type of additive: cells obtained from an insect cell line. When a vaccine is manufactured, the virus must be replicated in an environment friendly to it. Commonly, the cells used for this purpose are derived from yeasts, but occasionally, if a suitable yeast species cannot be found, the cells are obtained from animal species. The manufacturers of Cervarix solved some viral problems by using insect cells for replication. In the past, some viruses and other infectious agents have contaminated vaccines that have been made with animal cells.¹¹1 Cervarix is currently undergoing further testing for the FDA.

Safety in Preadolescents

When Gardasil was approved in June 2006, the FDA also recommended that it be administered to females between the ages of 9 and 26. This is despite the fact that, in the studies published to date, the vaccines were administered only to girls 15 and older.¹² While Merck states that a smaller study was performed using Gardasil with girls between 10 and 15 years to check the immune response in that age group, the study did not assess safety beyond 14 days after administration.¹³ This study was not published, and therefore is unavailable to be read by the public and is not subject to peer review by the medical community.

The recent track record of the FDA does not instill much faith in the institution's integrity in assessing the safety of new products. The most obvious example is the recent Vioxx debacle. After having been on the market for five years, Vioxx—a prescription medication used for arthritis and acute pain (and also made by Merck)—was withdrawn in September 2004 because it was found to cause a significant increased risk of heart attack and stroke.¹⁴ In fact, this risk was so great that the study was discontinued before it could be completed. There is now considerable question about how much information Merck and/or the FDA concealed during the approval process for Vioxx in 1999.

Another more relevant but less well-known example of the FDA's fallibility is what happened when adolescents began taking the antidepressant Prozac. Prozac and other drugs in its class were widely prescribed to adolescents for a variety of issues, from mood disorders to bulimia. Rising concern about Prozac's side effects among young people led to numerous studies,^15-17 the most recent of which was published in Archives of General Psychiatry in 2006.¹⁸ The results confirmed what had long been suspected and what other studies had shown: that Prozac caused a modest increase in the number of suicides when compared to a group of adolescents taking a placebo. Depressed teens who took Prozac were actually more likely to attempt suicide than depressed teens who took no medication at all.¹⁹ However, the FDA continues to recommend Prozac for pediatric and adolescent patients. Aside from calling the FDA's safety assurances into serious question, this also illustrates how a drug's proven success in studies undertaken with adults cannot be presumed to hold true for children and teens.

Gardasil and Public Health

The FDA categorized Gardasil as a drug that has the potential to provide "significant health benefits."²⁰ But exactly how big is the current risk of cervical cancer in the US? There is no doubt that, every year, the disease kills American women. However, cervical cancer is not usually a quickly progressing, invasive cancer. And it generally responds well to treatment. It is also true that the vast majority of women with cervical cancer are infected with HPV. On the other hand, the vast majority of women infected with HPV never get cervical cancer.

This brings into question cause and effect. In the journal Vaccine, Anna-Barbara Moscicki states that, "Given the ubiquity of HPV, the most critical step in cervical carcinogenesis [cancer initiation] is not acquisition of the infection, but rather the step involving progression to clinically important lesions."²¹ In other words, it's not getting HPV that matters, it's what happens afterward. Cervical cancers diagnosed in their early stages are rarely fatal. Most fatalities are due to lack of detection and treatment. The important keys to the prevention of cervical cancer are getting regular testing with annual Pap screens and modifying other risk factors. Getting early treatment is also important.

One Step Forward, Two Steps Back?

Regular Pap tests have reduced the rate of death from cervical cancer by at least 75 percent since the 1960s.²² Compared to screening for other types of cancer, Pap screening is considered by health-care practitioners to offer one of the best ratios of screening to actual prevention. It was no small feat for the public health community to establish annual Pap screening for women in the US, but it was worth the effort. Vaccination against HPV could change all of that.

The way Gardasil is being hailed in the media and advertisements, it is easy to understand how a young woman vaccinated with it might think that she has been protected against cervical cancer. Merck's campaign slogan, "One Less," implies that each woman who receives a Gardasil vaccination will be one less victim of cervical cancer. However, this idea of sure protection against cervical cancer is not only untrue but dangerous. Gardasil prevents infection by only four of the more than 100 strains of the HPV virus.²³ This is why it is thought that the vaccines will prevent, at most, only 70 percent of cervical cancers. But what if women infected with the other 30 percent of the cancer-causing strains of HPV decide to forgo their annual exams because they have been vaccinated with Gardasil and thus believe they are protected? Overall, we would see a decrease in the number of HPV infections, but a large increase in fatalities from cervical cancer. The public research has not yet been done to see if this effect would occur.

Greg Zimet, PhD, a clinical researcher at the Indiana University School of Medicine, has published several articles in medical journals about Gardasil. Although in favor of the vaccine, he concedes that a reduction in the number of women getting annual Pap tests might be an "unanticipated cost" of the vaccine's approval by the FDA; he emphasizes that "this does not change the need for regular Pap testing."²⁴ After 30 years of success in the public health sector with Pap tests and cervical cancer screenings, it would be a shame to backslide now.

Compare the statistics of cervical cancer in the US to those in places where the rates of cervical cancer and death from it are still high. In Haiti, the poorest country in the Western Hemisphere, cervical cancer accounts for nearly half of cancer deaths; in the US, 2.5 percent.²⁵ Regular screenings make the difference. In places such as Haiti, where most people cannot afford and/or have no access to regular screening, Gardasil may be just what the doctor ordered. However, Gardasil is an expensive vaccine, and is not marketed toward or currently available to these poorer populations; and in the US, it may actually cause more deaths from cervical cancer.

Another issue that only long-term research will resolve is how long a single vaccination with Gardasil will provide protection. So far, trials have shown that it sustains an immune response for five years, but it is still far too early to know whether immunity granted by Gardasil is lifelong or temporary. Knowing this will have a large impact on when, how, and if young women should be vaccinated.

A Costly Experiment

Do Gardasil's potential benefits outweigh the risks? Perhaps, but only time will tell. If it is similar to the hepatitis B vaccine introduced some years ago, it is still far too soon to know. "As shown by research on hepatitis B vaccination, many key answers only became known at least ten years after the vaccine first became available," states Eduardo Franco, of McGill University, Montreal, Canada, in Vaccine.²⁶

The bottom line is that we don't yet have enough information to know whether young women should be vaccinated en masse with Gardasil. We know that it is effective in conferring immunity against HPV. What we don't know is if it is safe to use with adolescents. Nor do we know anything about its long-term safety and efficacy with any age group. Nor do we know if mass vaccinations will cause a decline or an increase in deaths from cervical cancer. Considering how little we know, are we ready to make an entire nation of preadolescent girls the subjects of a vast experiment? At $360 for the full series of three injections, it will be challenging to even find the funding for a national vaccination campaign. Gardasil is one of the highest-priced vaccines ever marketed.²⁷ It is a costly risk to take.

For the notes to this article, see www.mothering.com/articles/growing_child/vaccines/guard-against-gardasil-notes.html.

Dr. Elissa Mendenhall is a naturopathic physician who lives in Portland, Oregon. Last summer, Dr. Mendenhall published original research on herbs and immune activity in Phytotherapy Research and, assisted by naturopathic midwives, gave birth to a baby girl at home.