Sex & fertility

Women to Women gives Gardasil guarded reviews

Questions on the long-term safety, global availability, and sexual politics of the new HPV vaccine

Gardasil targets four out of 100 human papilloma viral strains

Gardasil, the newly FDA–approved vaccine against human papilloma virus, is designed to protect women against infection by four separate strains of the virus. Over 100 strains of the HPV virus have been described, approximately 30 of which can affect the human reproductive tract. The four strains targeted by Gardasil comprise:

• #16 and #18, the two strains out of more than 20 oncogenic (cancer-causing) types that are responsible for 60–70% of cervical cancer cases; plus
• #6 and #11, two of the many other strains associated with genital warts.

Gardasil is being hailed as “one of the major health advances of the early 21st century.” As the first vaccine specifically designed to prevent cancer, Gardasil does make for an exciting start in the race to cure cervical cancer, but huge hurdles lie ahead before we cross the finish line.

How does the vaccine work?

In manufacturing Gardasil, New Jersey–based pharmaceutical giant Merck & Co. utilizes DNA technology invented at the National Institutes of Health and licensed for commercial development, isolating empty shells of viral structural proteins called virus-like particles (VLP’s) to serve as the vaccine’s active agents. The way VLP’s work is by triggering the recipient’s immune system to create antibodies against these four specific viral strains, without causing a full-blown infection and subsequent development of cancer.

To be most effective, Gardasil injections must be given in three doses over a six–month period to women who have had no prior exposure to the four strains of the viruses from which it offers protection. It offers no protection from the other cervical cancer-causing HPV strains.

FDA grants blanket approval — warts and all

The data submitted to the FDA represented tests conducted on 27,000 girls and women ages 9 through 26 and boys ages 9 through 15. The makers are now lobbying to mandate vaccination for little girls, while the FDA reports that the data are insufficient to support approval for boys and that separate trials for men and boys are currently under way.

Initial reports of the vaccine’s efficacy first came in 2002 when the New England Journal of Medicine described a trial (funded by Merck) in which nearly 1200 young women (ages 16–23) were vaccinated and an equivalent number given placebo injections. After following the subjects for a median of 17 months, the researchers found the vaccine to be 100% effective: none of the vaccinated women developed either infection or precancerous changes, while 41 of the nonvaccinated women did become infected, and nine of the latter developed precancerous cervical growths.

Since then, Merck has tested the vaccine on approximately 25,000 additional males and females in 33 countries, ages 9–26 and declared the drug to be safe and 100% effective. Richard Haupt, executive director of medical affairs with Merck’s Vaccine Division, says the vaccine is most effective when given to girls as young as nine years of age, before they become sexually active. That’s because trial subjects who had already had exposure to the four strains showed higher rates of cervical neoplasia (abnormal cancer cell precursors), raising questions as to whether the vaccine impairs immune response under such circumstances, or whether there were demographic factors at play, or both.

Company hails Gardasil as “Holy Grail,” belying more sobering aspects

While the physical side effects of the vaccine itself are reported as “minor” — pain, swelling, redness, fever, and itching at the site — we can’t help but ask for more details. Every vaccine contributes to the “load” on our immune systems and shouldn’t be taken lightly. Some of the missing pieces that need careful weighing before we would recommend the HPV vaccine to our patients include the following:

• What are the various ingredients used in this vaccine?
  Historically, cattle, dogs, rabbits, mice, and insects have all played a role in the development of this vaccine, but which plant or animal proteins are being used as a substrate today in Gardasil production? What chemicals are used in the vaccine suspension? We’ve read that it contains aluminum; do the preservatives contain other metals, such as mercury or other potential neurotoxins?

• What are its possible interactions with medications, e.g., psychoactive drugs, antihypertensives, HRT, cholesterol-lowering agents?

• Are there any side effects seen in subsets of patients with medical conditions such as diabetes, attention deficit hyperactivity disorder (ADHD), seizure disorders, allergies and sensitivities (e.g., to yeast), and above all, the immunosuppressed?

• Is it really safe for preteens?
  The FDA has approved use of the vaccine for females between the ages of nine and 26. In Merck’s trials, however, only 250 nine-year-old girls and boys were tested with Gardasil. Where did these kids come from? The other question we ask ourselves is, “Would I volunteer my nine-year-old daughter to test a vaccine against a sexually transmitted disease?”

• How long will protection last? Will boosters be needed? Or worse, will elimination of just four out of over 100 viral strains create a niche for other strains to fill?
  Swimming in its own vast gene pool and with billions of human hosts at hand, HPV has quite a survival advantage. What will happen to the niche currently occupied by strains # 16, 18, 6 and 11, if they are eliminated through vaccination? Microorganisms enjoy an extremely short life-cycle relative to ours, giving them the evolutionary edge when it comes to developing resistance against the very drugs and vaccines (and pesticides) we employ to annihilate them.
  
  We cannot exactly say the protection Gardasil affords is narrow, because the strains it targets cause an estimated 70% of cervical cancer cases and an estimated 90% of genital wart cases. Still, these figures are predictive and do not apply globally; moreover, things change fast in the microscopic world. Given the existence of at least 12 other high-risk HPV strains, could an opening arise for more virulent strains to emerge, should the vaccine succeed in decimating these particular four?
  
  For example, there are pockets in Africa where #45 is most common, whereas it ranks third in many other geographic areas, and a 2006 study suggests there has been an increase in HPV subtype heterogeneity from 1930–2000. This is not uncommon in nature. According to studies profiling HPV types, most populations tested are complex. HPV, like the flu, can be deadly, or no big deal. But if you want to vaccinate those most vulnerable, you may need to do it again at regular intervals, as waves of variants sweep in.

• The question to ask then is, “Who really needs it?” Isn’t there a greater call for an inexpensive vaccine in developing countries than for mandating an expensive one in American school systems?
  
  Analysts estimate annual sales could generate up to $3 billion for the pharmaceutical giant Merck through the life of the patent. At $360 per course, Gardasil is well beyond affordability for the vast majority of women who are at highest risk of developing cervical cancer: the underinsured and those in the poorest nations. The major reason behind the lower morbidity from cervical cancer in developed nations is that women here have greater — though far from perfect — access to regular gynecological exams and Pap screening, which, together with HPV DNA testing and improved treatment options, allow for early detection and interception — before cancerous cells have had time to develop. It is this combination that has dropped cervical cancer from the number–one cause of malignancy deaths in American women to eleventh overall since the introduction of the Pap test in the 1950’s.
  
  Meanwhile, on a global scale, cervical cancer continues to rank as the number-two cancer-related cause of death in women — 80% of all cases occur in developing nations (morbidity is highest in sub-Saharan Africa, South Asia, and Latin America). And while most insurance carriers in the US are expected to cover the cost of vaccination in young female subscribers, and Merck plans to provide free vaccines to uninsured adults meeting low-income guidelines, there remain billions of women worldwide for whom access to the vaccine is doubtful.
  
  According to a 2005 article in New Scientist, the International Agency for Research on Cancer in Lyon, France estimates that by 2050, deaths from cervical cancer could “reach a million a year in poor countries if rates of infection, and of cancer detection and treatment, do not improve.” According to their own press release, Merck is partnering with India’s Council of Medical Research to study Gardasil, and also has plans to collaborate with PATH and the Gates Foundation to facilitate introduction of Gardasil to impoverished nations. Adequate cervical screening programs can control HPV-caused cervical neoplasia, but if vaccines are more cost-effective in preventing cervical cancer than regular gyn exams and routine Pap screening — another healthcare “luxury” few women worldwide have access to — to what lengths are we prepared to go to ensure affordable global distribution of this vaccine?

• Where have all the young men gone?
  On another note, if our desire to protect women from cervical cancer is genuine, when would such a vaccine be ready for administration to men and, for that matter, when will boys and men be lined up to receive it? Some speculate that the reason protection is afforded against two genital wart strains by the vaccine is not simply because, as the company describes it, the presence of infection from the two strains can be a confounding factor in determining exposure to oncogenic strains, but because men worry most of all about the cosmetic impact of contracting genital warts, so having resistance to warts would lend cachet to having the vaccination.

We don’t believe any woman, anywhere, should have to suffer from cervical cancer. We have the means to prevent it, but do we have the will? Short of answers to all these questions, it appears to us that even if Gardasil does represent the beginning of an end to cervical cancer, there’s a long and winding road ahead. And we’re not alone in taking a cautious approach — the National Women’s Health Network recommends we wait to evaluate the HPV vaccine over time before making it mandatory. In the meantime, we’ll stand by, ready to offer women regular gynecological screening, Pap screening, HPV DNA testing, and the intervention methods shown most effective to date in preventing cervical cancer deaths.

For more information, see:

• HPV, genital warts, and Pap smears
• References and further reading
• HPV vaccine press release

 

Last Modified Date: 04/19/2011
Principal Author: Marcella Sweet