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Gardasil is a vaccine against certain types of the human papillomavirus (HPV), created by researchers Dr. Albert Bennet Jenson and Dr. Shin-je Ghim at the University of Louisville in 2006, following on research done by Professor Ian Frazer of Australia in conjunction with Australian biomedical company, CSL Limited. The vaccine, marketed by Merck & Co. in America, whilst paying royalties to CSL, is designed to prevent infection with HPV types 16, 18, 6, and 11. HPV types 16 and 18 cause about 70% of HPV-related cervical cancer cases. In addition, some types of HPV, particularly type 16, have been found to be associated with oropharyngeal squamous-cell carcinoma, a form of throat cancer. HPV types 6 and 11 cause about 90% of genital wart cases. Human papillomavirus (HPV) infection causes virtually all cases of cervical cancer, the 7th most common cause of death from cancer among women worldwide.

Biotechnology

The HPV major capsid protein, L1, can spontaneously self-assemble into virus-like particles (VLPs) that resemble authentic HPV virions. Gardasil contains recombinant VLPs assembled from the L1 proteins of HPVs 6, 11, 16 and 18. Since VLPs lack the viral DNA, they cannot induce cancer. They do, however, trigger an antibody response that protects vaccine recipients from becoming infected with the HPV types represented in the vaccine.

Prevalence of Genital HPV in the American Population

According to the Centers for Disease Control, by the age of 50 more than 80% of American women will have contracted at least one strain of HPV. HPV is highly communicable. Condoms do not protect against HPV. ]

All women are encouraged get a yearly pap smear solely to detect cancer cells caused by HPV.

Both men and women are carriers of HPV. To eradicate the disease, men will eventually need to be vaccinated. Studies are being conducted now to determine the efficacy of vaccinating boys with the current vaccine.

12,000 Americans die from cervical cancer every year, and there are thousands more who are treated for cervical cancer by freezing the cervix with liquid nitrogen or hysterectomy.

Safety and Efficacy of the Vaccine

According to the Centers for Disease Control, the vaccine was tested in over 11,000 girls (ages 9 to 26). These studies have shown no serious side effects. The most common side effect is soreness at the injection site. CDC, working with the FDA, will continue to monitor the safety of the vaccine after it is in general use. The vaccine does not contain mercury, thimerosal or live virus (only dead virus).

The National Cancer Institute claims, "FDA-approved Gardasil prevented nearly 100 percent of the precancerous cervical cell changes caused by the types of HPV targeted by the vaccine for up to 4 years after vaccination." ]

Public Health Concerns

The National Cancer Institute writes, "Widespread vaccination has the potential to reduce cervical cancer deaths around the world by as much as two-thirds, if all women were to take the vaccine and if protection turns out to be long-term. In addition, the vaccines can reduce the need for medical care, biopsies, and invasive procedures associated with the follow-up from abnormal Pap tests, thus helping to reduce health care costs and anxieties related to abnormal Pap tests and follow-up procedures (2)."

Clinical Trials

Merck & Co. conducted a Phase III study named FUTURE II. This clinical trial was a randomized double-blind study with one controlled placebo group and one vaccination group. Over 12,000 women aged 16-26 from thirteen countries participated in the study. Each woman was injected with either Gardasil or a placebo on Day 1, Month 2, and Month 6. In total, 6,082 women were given Gardasil and 6,075 received the placebo. Merck has tested the vaccine in only a few hundred 11- and 12-year-old girls.On February 27, 2006, the independent Data and Safety Monitoring Board recommended the clinical trials be terminated on ethical grounds, so that young women on placebo could receive Gardasil.

Administration

The US Food and Drug Administration (FDA) approved Gardasil on June 8, 2006. Gardasil is currently available. The drug is also approved for use in Australia, New Zealand, Canada, Mexico, Croatia, Malaysia, Brazil, Serbia, and countries of the European Union.

Gardasil is given in three injections over six months, namely at enrollment, and two and six months later.

Adverse effects can include local limited reactions at the site of injection, such as pain, swelling, redness, and itching. Other adverse effects, including seizures, fevers, joint pain, lack of consciousness, and Guillain-Barré syndrome, have been filed with VAERS; because these events resulted from complex real-life situations and not controlled tests, it is difficult to determine what role, if any, Gardasil played in these episodes.

On June 29,2006, a panel of experts, the Advisory Committee on Immunization Practices, gave their approval for the vaccination of Gardasil on children as young as nine years old. The ACIP recommended that Gardasil be placed on the childhood immunization schedule at the eleven to twelve year old visit. They also recommended that the vaccine be included in the federal Vaccines for Children Program, which would provide the vaccines free of charge to children under the age of eighteen who are uninsured.

Government Mandates

According to the Centers for Disease Control, getting as many girls vaccinated as early and as quickly as possible will reduce the cases of cervical cancer among middle-aged women in 30 to 40 years and reduce the transmission of this highly communicable disease. Unfortunately, there are hurdles to getting this done. These include the limited understanding by many people that HPV causes cervical cancer, the difficulty of getting pre-teens and teens into the doctor’s office to get a shot, and the high cost of the vaccine (more than $360 per dose).

One way to bring down the cost of the vaccine and to educate the public on the benefits of vaccination is to make it mandatory for girls entering school. This approach has been taken with vaccines for mumps, measles, rubella, and hepatitis (which is also sexually transmitted) so many state legislators have penned bills that do this.

Almost all legislation currently pending in the states that would make the vaccine mandatory for school entrance have an "opt-out" policy. .

Criticisms

Phyllis Schlafly said that Merck engaged in a "lobbying campaign to make this vaccine compulsory". (It may be noted here that GlaxoSmithKline is currently in Phase III trials for its own vaccine, “Cervarix,” soon to bring another competitor into the field.)

State Legislation

Legislation has been introduced in the state of Michigan to make Gardasil mandatory. After the failure of SB 1416 in December, the first attempt to mandate this vaccine, it is uncertain if this legislation will pass.

Texas Governor Rick Perry issued an executive order on February 2,2007 mandating the vaccine be given to all school girls entering sixth grade, beginning September 2008. This ruling would allow parents to opt out of vaccinating their daughters. On February 22, 2007 a group of Texas families filed a lawsuit to stop the executive order. It is to be noted that an executive order is not a law but rather a recommendation. On April 25, 2007, the Texas legislature overruled Governor Perry's order, forbidding mandatory vaccination until at least 2011.

In Australia, the Australian government and the PBS (Pharmaceutical Benefits Scheme) has approved the vaccine for use and in 2007 began a nationwide vaccination program free of charge to schoolgirls in years 10, 11 and 12. These programs are run by local councils with funding and vaccine supplies coming from the government.

Opponents of the order say that the $360 cost of the vaccine plus several hundred dollars in physician visits to receive the three treatments necessary for vaccination would be better spent on providing pap smears to these patients. Pap smears are currently the gold standard for detecting and treating neoplasia of the cervix and preventing cervical cancer from developing. Additionally, they note that Rick Perry's former Chief of Staff is a member of Merck's Texas lobbying team, and that Governor Perry received $6000 in campaign contributions from Merck in his last campaign. Since Gardasil is patented, Merck is the sole producer.

New Hampshire has adopted a voluntary program, in which it supplies the vaccine free of charge to girls between the ages of 11 and 18. This has met with wide acceptance, with many young women requesting the vaccine. South Dakota and Washington are considering similar measures.

Australia's government announced on 29 Nov 2006 that they will provide this vaccination to all 12-26 year-old women in 2007. After two years, the program will be scaled down to 12-13 year old girls only. Australia also approved Gardasil for boys 9-15 years old, but Australia is not providing government funding for vaccinating boys. On March 26, 2007, early approval was granted in both Germany and Italy.

Other states are also preparing bills to handle the issue of this HPV Vaccine:

Source: National Conference of State Legislatures, state legislatures

Long-Term Impact

One unknown property of the vaccines now being researched is their longevity. Since the studies have been of short duration, it is unknown whether the vaccines will last just a few years or for much longer. Further study over time is required to answer this question.

270,000 women died of cervical cancer worldwide in 2002. Acting FDA Administrator Dr. Andrew von Eschenbach said the vaccine will have "a dramatic effect" on the health of women around the world. The American Cancer Society estimated that 9,700 women would develop cervical cancer in the United States in 2006, and 3,700 would die.

Merck and CSL Limited are expected to market Gardasil as a cancer vaccine, rather than an STD vaccine. It remains unclear how widespread the use of the three-shot series will be, in part because of its $360 list price ($120 each for three shots). Merck and CSL have also suggested that governments make vaccination with Gardasil mandatory for school attendance, which has upset some conservative groups. Many such groups also expressed fears that vaccination with Gardasil might give girls a false sense of security regarding sex and increase their level of promiscuity. There is no scientific evidence to prove this claim.

Health freedom organizations and other critics of the political power of pharmaceutical companies have vocally denounced the mandatory vaccination scheme as Merck's way of using forced drugging to pay for Vioxx lawsuits.

Another potential issue is that it is not known whether this vaccine has any long-term adverse side effects. Although it has undergone full FDA trials, some fear that detrimental effects may not appear until years or decades after exposure.

Indications

Gardasil is a prophylactic HPV vaccine, meaning that it is designed to prevent the initial establishment of HPV infections. In worldwide clinical analyses, however, women who were already infected with one or more of the four HPV types targeted by the vaccine (6, 11, 16, or 18) were protected from clinical disease caused by the remaining HPV types in the vaccine. For maximum efficacy, it is recommended that girls receive the vaccine prior to becoming sexually active. Since Gardasil will not block infection with all of the HPV types that can cause cervical cancer, the vaccine should not be considered a substitute for routine Pap smears. About 10,000 cases of cervical cancer are diagnosed annually in the United States, totalling around 9700 deaths. The lifetime risk of cervical cancer for women in the U.S., estimated by the National Cancer Institute, is 0.73%.

Fewer HPV infections mean fewer complications from the virus and less time and money spent on the detection, work-up, and treatment of cervical cancer and its immediate precursor, cervical dysplasia. It prevents infertility caused by cervical biopsies and reduces the severe respiratory problems of children who inherit HPV from their mothers. In addition, protection against HPV6 and HPV11 also eliminates 90% of the cases of genital warts. Gardasil also may be useful in preventing anal cancer caused by HPV types 16 and 18. A 2005 study in San Francisco found that 95 percent of HIV-infected gay men also had anal HPV infection, of which 50 percent had precancerous HPV-caused lesions.

No Adverse Effects

The vaccine has no side effects with the exception of soreness around the injection area. The FDA and CDC consider the vaccine to be completely safe. It does not contain mercury, thimerosal or live virus (only dead virus).. Merk, the manufacturer of Gardasil, will continue to test women who have received the vaccine to determine the vaccine's efficacy over the period of a lifetime.

Both men and women are carriers of HPV. To eradicate the disease, men will eventually need to be vaccinated. Studies are being conducted now to determine the efficacy of vaccinating boys with the current vaccine.

References

1. D'Souza, Gypsyamber; Kreimer, Aimee R.; Viscidi (May 10, 2007). "Case–Control Study of Human Papillomavirus and Oropharyngeal Cancer". New England Journal of Medicine. 356: 1944–1956. {{cite journal}}: Unknown parameter |first 3= ignored (|first3= suggested) (help)CS1 maint: date and year (link)
2. Cancer Research UK The most common causes of death from cancer worldwide, 2002 estimates. accessed 22 May 2007
3. "Merck's Investigational Vaccine GARDASIL™ Prevented 100 Percent of Cervical Pre-cancers and Non-invasive Cervical Cancers Associated with HPV Types 16 and 18 in New Clinical Study". 2005-10-06. Retrieved 2007-01-26.
4. "Gardasil Efficacy Questioned by Experts says Wall Street Journal". Vaccine Rx. 2007-04-16. Retrieved 2007-04-16.
5. ROBERTS, J. (2007-02-27). "Gardasil Trials End on Tuesday Due To Success". Vaccine Rx. Retrieved 2007-02-27.
6. ^ FDA approves cervical cancer vaccine, AP, accessed June 8, 2006
7. Analysis of Vaccine Adverse Events Reporting System Reports, National Vaccine Information Center, accessed January 31, 2007
8. Panel approves Gardasil usage, AP, accessed June 30, 2006
9. Barillas, Martin (2006-09-14). "GARDASIL vaccine touted in Michigan". Spero News. Retrieved 2007-01-26.
10. PETERSON, LIZ AUSTIN (2007-02-02). "Texas Gov. Orders Anti-Cancer Vaccine". Washington Post. Retrieved 2007-02-02.
11. "Cervical Cancer Vaccine Blocked By Texas Families". Vaccine Rx. 2007-02-24. Retrieved 2007-02-24.
12. Blumenthal, Ralph (2007-04-26). "Texas Legislators Block Shots for Girls Against Cancer Virus". New York Times. Retrieved 2007-04-26.
13. Belluck, Pam (2007-05-12). "In New Hampshire, Soft Sell Eases Vaccine Fears". New York Times. Retrieved 2007-05-15.
14. Poljak, Vesna (2006-11-29). "Australia to Subsidize Merck Cervical Cancer Vaccine (Update3)". Bloomberg. Retrieved 2007-01-26. {{cite news}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
15. Fagbire, OJ (2007-03-26). "Gardasil, Merck HPV Vaccine, Gets German And Italian Approval For Girls". Vaccine Rx. Retrieved 2007-03-27.
16. Carreyrou, John. "Questions on Efficacy Cloud a Cancer Vaccine". Wall Street Journal.
17. Cohen J. 2005. High Hopes and Dilemmas for a Cervical Cancer Vaccine. Science, 308(5722): 618-621.
18. National Cancer Institute SEER fact sheet on cervical cancer accessed 30 Mar 2007
19. Moral majority take on GSK and Merck over cancer drugs, accessed June 12, 2006
20. Barillas, Martin (2006-09-14). "GARDASIL vaccine touted in Michigan". Spero News. Retrieved 2007-01-26.
21. Moral majority take on GSK and Merck over cancer drugs, accessed June 12, 2006
22. Alliance for Human Research Protection against mandating Gardasil
23. A: A Cancer Journal for Clinicians
24. National Cancer Institute SEER fact sheet on cervical cancer accessed 30 Mar 2007.
25. An HPV vaccine - what it might really mean, Edwin J. Bernard, AIDSmap, October 24, 2005 (Accessed June 8, 2006)
26. HAART is not reducing risk of anal cancer in gay men, Edwin J. Bernard, AIDSmap, August 29, 2005 (Accessed June 8, 2006)

External links

• News and commentary on Gardasil from the Ethics of Vaccines project at the University of Pennsylvania Center for Bioethics
• A Cancer Vaccine is Born (press release from University of Rochester)
• Gardasil web site
• MedlinePlus on HPV
• CDC STD Human Papillomavirus (HPV) Infection
• iGardasil.com ("informational" website)
• Panel Unanimously Recommends Cervical Cancer Vaccine for Girls 11 and Up Gardiner Harris, 30 June 2006, The New York Times
• The Cervical Cancer Blog
• Blog Documenting Efforts to Overturn TX Gardasil Mandate
• FDA Product Approval Information - Licensing Action
• Data on clinical trials
• Advisory Committee on Immunization Practices Minutes

• Current events from April 2007
• Vaccines