August 2006, Volume 21, Number 8

A Closer Look
What If Preventing Cancer Is as Easy as Being Vaccinated?

Barbara A. Biedrzycki, RN, MSN, AOCN^®, CRNP
Contributing Editor

If we knew how to prevent cancer, would we? The Surgeon General issued a groundbreaking report in 1964 stating that cigarette smoking is known to cause cancer, but many still ignore the warning and continue to smoke. Smokers have many convincing rebuttals: Cigarettes are physically and psychologically addictive, quitting is not easy, and nicotine replacement and will power often are not enough to facilitate quitting.

What if avoiding a carcinogen did not have those associated challenges? What if preventing one type of cancer was as easy as being vaccinated? And what if that type of cancer was the second most common worldwide cause of female cancer deaths? Would we use biotechnology to its full potential?

Incidence in the United States

According to the Centers for Disease Control and Prevention ([CDC], 2006a, 2006b),

• Human papillomavirus (HPV) is the most common sexually transmitted disease (STD).
• 20 million men and women are infected.
• HPV is most common in people in their late teens and early 20s.
• 80% of women are infected by age 50.

Cervical cancer is unlike most cancers. It is a "rare complication of a very common infection" (Crosbie & Kitchener, 2006, p. 544). HPVs, a group of more than 100 viruses, are the major cause of cervical cancer. They also play a role in cancers of the anus, vulva, vagina, and penis and some cancers of the oropharynx. More than 30 types of HPV are known to be transmitted sexually, and half of them are considered to be high risk for the development of cervical cancer.

Healthcare professionals have a unique opportunity to detect and prevent cervical cancer because it has a well-defined precancerous state, the cervix is accessible for screening and treatment, and the cause (HPV) is known (Crosbie & Kitchener, 2006). Although HPV infection may last for months or years, most people are able to clear the infection through the immune system (Lowy & Schiller, 2006).

Women are most at risk for high-grade cervical dysplasia when an HPV type 16 or 18 infection lasts for more than six months. Left untreated, the persistent dsyplasia can transform into a lethal cancer (Lowy & Schiller, 2006).

Research and Development

Two major pharmaceutical companies, GlaxoSmithKline (Research Triangle Park, NC) and Merck & Co., Inc. (Whitehouse Station, NJ), were competing to be the first to get an HPV vaccine to market. GlaxoSmithKline's HPV vaccine, Ceravix™, demonstrated 100% efficacy against the precancerous lesions associated with HPV types 16 and 18 for 4.5 years (Harper et al., 2006). Merck's HPV vaccine, Gardasil^®, protects against cervical cancer, precancerous lesions, and cervical dysplasia associated with types 16 and 18. In addition, Gardasil protects against the HPV types that are responsible for 90% of genital warts, types 6 and 11 (Merck & Co., Inc., 2006a).

Both HPV vaccines were administered in research studies as three intramuscular injections over a six-month period. The U.S. Food and Drug Administration (FDA) granted unanimous approval of Merck's Gardasil investigational new drug application on June 8, 2006. Ceravix is still under the FDA's review.

National Recommendations

"Today is a historic day," said Anne Schuchat, MD, director of CDC's National Center for Immunizations and Respiratory Diseases, at a June 29 press conference announcing that the United States was the first country to make a national vaccination recommendation for HPV (CDC, 2006a). The announcement was made shortly after the Advisory Committee of Immunization Practices (ACIP) voted unanimously to recommend that Gardasil be given to 11–12-year-old girls. Although the 11–12 age group will be targeted, ACIP emphasized that the vaccine can be used until age 26 and, at healthcare providers' discretion, as early as age 9 (CDC, 2006b).

After FDA approval, ACIP considers the efficacy, safety, and cost effectiveness of a vaccine before it makes its recommendations. ACIP has resolved that the HPV vaccine be included in the Vaccination for Children (VFC) Program, a national effort that provides free immunizations to children who are Medicaid eligible, uninsured, underinsured, or Native American. The guidelines became official when published in the CDC's Morbidity and Mortality Weekly Report (CDC, 2006a).

Keep in mind that the recommendations are not national mandates. Each state independently determines its own vaccination mandates for school-age children. The VFC program provides access to the HPV vaccine for some children. Health insurance providers customarily consider the recommendations of the ACIP when deciding their coverage benefits (CDC, 2006a). Access for uninsured or low-income adults will be strengthened by Merck's (2006b) assistance program.

"About 40%–45% of the U.S. child population is included in the VFC," said Lance Rodewald, MD, of the Immunization Services Division. He indicated that, usually within the first year of a recommendation being issued, about a fifth of the population will be vaccinated; after several years, expectations are for 90% coverage (CDC, 2006a).

A Potential Yet Preventable Global Epidemic

In the United States, cervical cancer once was a major cause of cancer deaths. But now, mainly because of the Papanicolaou (Pap) test, death rates from cervical cancer continue to decline by almost 4% per year (American Cancer Society, 2005). In developing countries, cervical cancer is responsible for 15% of all cancer deaths, yet those countries have only 5% of the world's cancer resources available. Access to testing and treatments is why 70% of women with cervical cancer in the United States live and why 59% of women with cervical cancer in developing countries die (World Health Organization, 2006).

Future Directions

Research already is under way to develop advanced HPV vaccine technology. Perhaps therapeutic vaccines can be developed to prevent cervical cancer after HPV exposure or after the development of cervical dysplasia, carcinoma in situ, or invasive cervical cancer. Perhaps a more feasible delivery system for distribution of the HPV vaccine can reduce the cost and increase use in developing countries.

About 75% of the 4.7 million abnormal Pap tests that require costly follow-up every year are related to HPV (Merck & Co., Inc., 2006b). Merck estimated that five billion healthcare dollars are spent in the United States annually on HPV-related disease. In addition to expenses, high stress levels associated with repeated testing and the ever-present threat of cervical cancer may be eliminated with the HPV vaccine.

Even though HPV is an STD shared between the sexes, the HPV vaccine is targeted only to females, the sex at risk for the deadly sequela of HPV: cervical cancer. HPV vaccination of females could offer herd immunity to men and women.

References

American Cancer Society. (2005). What are the key statistics about cervical cancer? Retrieved June 29, 2006, from http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_cervi cal_cancer_8.asp?sitearea=

Centers for Disease Control and Prevention. (2006a). CDC press briefing: ACIP recommends HPV vaccination. Retrieved June 29, 2006, from http://www.cdc.gov/od/oc/Media/transcripts/t060629.htm

Centers for Disease Control and Prevention. (2006b). CDC's advisory committee recommends human papillomavirus virus vaccination [Press release]. Retrieved June 29, 2006, from http://www.cdc.gov/od/oc/Media/pressrel/r060629.htm

Crosbie, E.J., & Kitchener, H.C. (2006). Human papillomavirus in cervical screening and vaccination. Clinical Science, 110, 543–552.

Harper, D.M., Franco, E.L., Wheeler, C.M., Moscicki, A.B., Romanowski, B., Roteli-Martins, C.M., et al. (2006). Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18. Lancet, 367, 1247–1255.

Lowy, D.R., & Schiller, J.T. (2006). Prophylactic human papillomavirus vaccines. Journal of Clinical Investigation, 116, 1167–1173.

Merck & Co., Inc. (2006a). Gardasil^® [quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine] [Prescribing information]. Retrieved June 29, 2006, from http://www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf

Merck & Co., Inc. (2006b). Merck's new cervical vaccine, Gardasil^®, unanimously recommended by CDC advisory panel for vaccination of girls and women 11 to 26 years [Press release]. Retrieved June 29, 2006, from http://www.merck.com/newsroom/press_releases/product/2006_0629.html

World Health Organization. (2006). Controversial new vaccine to prevent cervical cancer. Retrieved July 29, 2006, from http://www.who.int/bulletin/volumes/84/2/news20206/en

Contributing Editor Barbara A. Biedrzycki, RN, MSN, AOCN^®, CRNP, is a research associate in the School of Medicine at Johns Hopkins University in Baltimore, MD.