Each year in the United States, more than 11,000 women are diagnosed with cervical cancer and close to 4,000 die of the disease.1 Worldwide an estimated 310,000 women die of cervical cancer each year. More than 80 percent of these deaths occur in developing countries, where cervical cancer is the leading cause of cancer death in women.2
These numbers, however, may drop substantially in coming decades. Vaccines against two high-risk types of human papillomavirus (HPV) have the potential to prevent an estimated 70 percent of cervical cancer cases; they are also expected to substantially reduce the risk of less common HPV-related cancers such as cancers of the vulva and the vagina. Gardasil® (Quadrivalent Human Papillomavirus [Types 6, 11, 16, 18] Recombinant Vaccine)-the HPV vaccine currently available in the United States-also protects against two additional types of HPV that cause roughly 90 percent of genital warts. “These are very effective vaccines,” says Dr. Lauri Markowitz, a medical epidemiologist at the Centers for Disease Control and Prevention (CDC).
Gardasil was licensed for use in the United States in June 2006, and a second HPV vaccine-Cervarix™-is expected to receive Food and Drug Administration (FDA) approval in 2008. What have we learned from the first two years of HPV vaccination? And what does the future hold?
Human papillomaviruses consist of more than 100 different viruses. Some types of HPV cause warts on the hands or feet, others cause genital warts, and some have been linked with cancer, most notably cervical cancer.
The types of HPV that are linked with cervical cancer and genital warts are transmitted sexually. Genital HPV infection is extremely common and generally occurs soon after an individual becomes sexually active. An estimated 45 percent of U.S. women between 20 and 24 years of age are infected with HPV.3 The prevalence of HPV infection is also high among U.S. teens. A recent study reported that one in four teenage girls (26 percent) has a sexually transmitted infection. HPV was the most common infection and was found in 18 percent of the girls in this age group.4
The likelihood that an HPV infection will develop into cancer depends in part on the HPV type and the persistence of the infection. Certain types of HPV have been more strongly linked with cancer than others and are referred to as “high-risk.” HPV types 16 and 18, for example, are high-risk types that are thought to account for roughly 70 percent of all cases of cervical cancer. In addition, among women infected with a high-risk type of HPV, persistent infection is the major risk factor for cervical cancer.
Infection with a high-risk type of HPV does not necessarily lead to cancer. Many infections disappear on their own,5 and others may persist without causing cancer. Infection with a high-risk type of HPV does, however, increase the risk of cancer, and virtually all cases of cervical cancer can be linked to infection with a high-risk type of HPV.
Gardasil, the HPV vaccine that is currently on the market in the United States, and Cervarix, a second HPV vaccine that has been submitted for FDA approval, are both intended to prevent infection with certain types of HPV; these vaccines do not treat existing HPV infections or cervical abnormalities.
Gardasil protects against HPV types 6 and 11 (which are linked with genital warts) as well as the cancer-associated types 16 and 18. Cervarix targets HPV types 16 and 18 only. Clinical trials of these vaccines suggest that they are safe and highly effective. The most common adverse effects reported in prelicensure studies of Gardasil were pain at the injection site, swelling, redness, and fever.6
In June 2006 Gardasil was approved for use in girls and women between the ages of 9 and 26 years. Because the vaccine is not effective against existing infections, it is likely to have the greatest effect when given before a girl becomes sexually active. The CDC’s Advisory Committee on Immunization Practices recommends routine vaccination of girls 11 to 12 years of age.7
An important point to keep in mind with both HPV vaccines is that they do not protect against all high-risk types of HPV. “Women who get HPV vaccine still need to get cervical cancer screening,” says Dr. Markowitz.
Gardasil: The First Two Years
Although Gardasil was shown to be safe and effective before being licensed in 2006, researchers have continued to monitor the safety and the efficacy of the vaccine as it’s moved from clinical trials to more-widespread use in the general population. The final results of large, ongoing postmarketing studies will not be available for some time, but in the meantime researchers have monitored reports to the Vaccine Adverse Events Reporting System (VAERS). VAERS is managed jointly by the CDC and the FDA and collects reports about adverse events following vaccination. These reports come from many sources, including healthcare providers, patients, and parents. VAERS reports can neither prove nor disprove that vaccination caused a particular adverse event (some events follow vaccination but are not caused by vaccination), but the information reported to VAERS allows researchers to identify potential areas of concern that warrant additional investigation.
Thus far, says Dr. Markowitz, VAERS reports haven’t raised any major concerns. There have, however, been reports of fainting after vaccination. “This is something that’s being looked into,” says Dr. Markowitz. “There’s been some concern about that, but one of the things that’s been known is that adolescents in general tend to have more fainting or syncopal episodes after vaccination or other exposure to needles.” The fainting episodes may therefore be a response to the needle rather than to the vaccine itself. “We’ve emphasized,” continues Dr. Markowitz, “that adolescents getting vaccine should be observed after vaccination in case they faint.”
The extent to which girls in the target age range are receiving the vaccine is still unknown, but information from national surveys of vaccine use is expected to be available soon.
What Does the Future Hold?
HPV vaccines have the potential to dramatically reduce the burden of precancerous and cancerous changes to the cervix by preventing infection with high-risk types of HPV, and the most current available evidence suggests that these vaccines are safe and effective. Nevertheless, some challenges and questions remain.
One of the challenges, according to Dr. Markowitz, is delivering three doses of the vaccine over a six-month period to adolescents who don’t normally have contact with the healthcare system on that schedule. “It’s not like younger children who come to the doctor more often or who know they need to come in to get childhood vaccinations.”
Questions also remain about how vaccine recommendations will address the expected approval of a second HPV vaccine, Cervarix. Differences between the two vaccines include the number of HPV types included (Gardasil protects against four types of HPV, and Cervarix protects against two) as well as the type of adjuvant used. An adjuvant is a component of the vaccine that enhances immune response. Cervarix and Gardasil use different adjuvants, and this may influence the strength and the duration of protection.
Use of HPV vaccines may eventually be expanded to a broader segment of the population. Studies in boys are under way, and vaccination of boys could offer several benefits: it would reduce transmission of the virus in the population (increasing the protection of girls) and would also protect boys against HPV-related conditions such as genital warts and cancer of the penis or anus.
Ongoing studies also suggest that Gardasil is effective in women over 26, and Dr. Markowitz notes that it’s possible that the vaccine will eventually be approved for older women. “But the main question,” she notes, “would be Is it really worthwhile? As women get older, they have less exposure to HPV and they have a higher chance of already being infected. So even if it’s approved by the FDA in those age groups doesn’t mean it would be recommended for routine use in those age groups.”
The future may also bring new types of HPV vaccines as well as HPV vaccines that target a broader range of HPV types. These new vaccines are not likely to reach the market anytime soon, however. “It takes years for vaccines to be developed, tested, and licensed by the FDA,” explains Dr. Markowitz. But regardless of what the future holds, the currently developed HPV vaccines are likely to have an important impact on women’s health both within the United States and around the world. The current HPV vaccines will not replace cervical cancer screening, but they are likely to improve the outcome of screening for many women by reducing the risk of both precancerous and cancerous changes to the cervix.
Centers for Disease Control and Prevention. Comprehensive information about HPV infections and HPV vaccination:
Vaccines for Children. A federally funded program that provides vaccines at no cost to children who might not otherwise be vaccinated because of inability to pay. Available to children through the age of 18 years. Includes the HPV vaccine:
Frequently Asked Questions
If I’m vaccinated, will I still need to be screened for cervical cancer?
Yes. The vaccine does not protect against all high-risk types of HPV.
Will Gardasil treat existing HPV infections?
No. The vaccine is intended to prevent infection with specific types of HPV. It will not treat existing infections or cervical abnormalities.
Can I become infected with HPV by being vaccinated?
No. The vaccine does not contain live virus and cannot cause infection.
What are the target age groups for vaccination?
The Advisory Committee on Immunization Practices recommends routine vaccination of girls ages 11 to 12 years. The vaccine can also be offered to girls as young as 9 as well as girls and women between the ages of 13 and 26.
Is there any reason to vaccinate boys?
Although the vaccine is not yet licensed for use in boys, vaccinating boys would likely provide important benefits: It would reduce transmission of the virus in the population and would also protect boys against HPV-related conditions such as genital warts and cancer of the penis or anus. The vaccine may be licensed for use in boys after more data become available.
How much does the vaccine cost?
As of February 8, 2008, the cost for three doses of Gardasil was $375.8 Gardasil is covered at least in part by many private insurers. Children who are uninsured or underinsured may be able to receive the vaccine through the federal Vaccines for Children program (www.cdc.gov/vaccines/programs/vfc).
How many doses of the vaccine are required?
The vaccine is given in three doses over a six-month period.
2. Garcia M, Jemal A, Ward EM, et al. Global Cancer Facts & Figures 2007. Atlanta, GA: American Cancer Society, 2007. Available at: http://www.cancer.org/downloads/STT/Global_Cancer_Facts_and_Figures_2007_rev.pdf. Accessed March 16, 2008.
4. Forhan SE. Prevalence of sexually transmitted infections and bacterial vaginosis among female adolescents in the United States: Data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004. Paper presented at: 2008 National STD Prevention Conference; March 10-13, 2008; Chicago, Illinois. Presentation D4a.
7. Markowitz LE, Dunne EF, Saraiya M, et al. Quadrivalent Human Papillomavirus Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report. 2007;56(RR-2):1-24.