Megan Cole, Diana Zuckerman, PhD, Brandel France de Bravo, MPH, and Janet A. Phoenix, MD, Cancer Prevention and Treatment Fund
What is HPV?
The human papillomavirus virus, also known as HPV, is the most common sexually transmitted infection-both in the U.S. and around the world. In fact, approximately 20 million Americans are currently infected with HPV, and another 6 million become newly infected every year. By age 50, 70-80% of all women will have contracted at least one strain of HPV. The virus is transmitted through skin-to-skin contact and is usually sexually transmitted-vaginally, anally, or sometimes, orally. However, many of the HPV types can be transmitted through non-sexual contact as well.
This virus may lead to several types of cancers in women, including cancers of the cervix, vulva, vagina, and anus. However, a person is much more likely to get cervical cancer than the other three cancers combined. There are approximately 130 strains of HPV, some of which may cause warts and others which may cause cancer. Of these strains, two types cause 70% of cervical cancer cases (strains 16 and 18) and two types cause 90% of genital warts cases (strains 6 and 11). Most HPV infections in adolescents are short term-70% of infections disappear within a year and 90% disappear within two years. However, while most HPV infections go away on their own, it is possible for abnormal cells to develop on the cervix, vulva, vagina or anus when high-risk types of HPV persist over time. If those high-risk abnormal cells (CIN 2, CIN 3 or HSIL, which stands for “high-grade squamous intraepithelial lesions”) are not detected and treated, they can eventually cause cancer.
It takes about 15-20 years for this to happen, and meanwhile, the women are unlikely to have symptoms. That’s why HPV can go undetected and cause cancer, especially for those without access to regular Pap smears or other medical care.
Although HPV and cervical cancer are a concern for all women, in the U.S., the women with the highest rates of cervical cancer are minority and low-income women. While far fewer women die of cervical cancer in the U.S. compared to many other countries, it is still a deadly disease for thousands of women every year. African-American women are twice as likely to die from cervical cancer as white women. One study found that cervical cancer rates for whites were 9.2 per 100,000, compared to 12.4 for African Americans and 16.8 for Hispanics. The same study reported death rates of 2.7 per 100,000 for whites, compared to 5.9 for African Americans and 3.7 for Hispanics.
When women die of cervical cancer, it is usually because they have not had a Pap smear in many years, if ever, and their cancer is caught very late. Pap smears detect cervical cell changes early on, helping to save lives. In fact, having a regular screening every 2 to 3 years greatly reduces a woman’s risk of getting cervical cancer. The widespread use of the Pap test has reduced cervical cancer in the U.S. by more than half over the past 30 years.
Poverty is a risk factor as well: a 2007 study showed that 23% of women living below the poverty line tested positive for high-risk HPV (strains 16 and 18), while only 12% of women living at least three times above the poverty line tested positive for high-risk HPV. This is probably due to lower-income women having fewer Pap smears.
To reduce your risk of death from HPV causing cervical cancer, the best strategies are:
1. Get regular Pap smears. They detect changes in the cervix caused by HPV.
2. Use condoms. They reduce your chances of getting infected with HPV but they don’t eliminate your risk, because skin-to-skin contact still occurs when a condom is used.
3. Limit your number of sex partners.
4. Get an HPV vaccine. HPV vaccines help protect against the most common types of HPV. The first HPV vaccine became available in 2006.
The HPV Vaccine
Gardasil was approved by the Food and Drug Administration (FDA) in June 2006 and received a lot of publicity as “the first cancer vaccine.” Gardasil is approved to protect girls and women, ages 9 through 26, from the two types of HPV infection that are responsible for 70% of cervical cancer cases and two other types of HPV infection that are responsible for 90% of genital warts cases. It has very limited effectiveness, however, against other types of HPV that cause approximately 30% of cervical cancers. For that reason, girls and women who are vaccinated with Gardasil will still need regular Pap smears to detect cervical cancer in its early stages when treatment is most effective. In 2008, Gardasil was also approved to protect against vaginal and vulvar cancers.
The Gardasil vaccine is administered in three doses over a six-month period. The vaccine data so far are short-term, and vaccine producer Merck states very clearly on the home page of its Gardasil website (www.Gardasil.com) that: “The duration of protection of Gardasil has not been established.”
Several clinical trials have been conducted, but most for under five years and none for 10 years or longer. We still cannot be certain whether Gardasil will be effective for all women for 5 years, nor do we know what percentage of women will be protected for longer than 5 years. Because cancers take so long to develop, we will not know the true impact of Gardasil on cervical cancer for several decades. It is important to know if Gardasil will require a booster shot in order for it to offer long-term protection, but those studies have not yet been conducted.
A second HPV vaccine, known as Cervarix, was approved by the FDA in October 2009. It is produced by GlaxoSmithKline and became available in May 2010. Cervarix was approved for use in girls ages 10 to 25, and like Gardasil, is given as a three dose series over six months. Cervarix costs about the same as Gardasil: on average, $385 for the three doses of the vaccine. Unlike Gardasil, Cervarix only protects against two HPV strains-types 16 and 18, which are the leading causes of cervical cancer. Like Gardasil, the long-term effectiveness is still unknown and the need for a booster shot to maintain protection is uncertain.
What’s the Difference Between the Two Vaccines? Are They Both Safe?
While no head-to-head studies have been done comparing the overall effectiveness of Cervarix and Gardasil, we do know about some differences. In clinical trials, Cervarix was shown to be 93% effective in preventing cervical pre-cancers associated with HPV 16 or HPV 18 in women-this means that it protects against abnormal cervical changes that could lead to cervical cancer. It may also provide protection against other strains of HPV, including types 45 and 31, which also cause cervical cancers. In clinical trials, Cervarix was 75% effective at protecting against three cancer-causing types of HPV that are not part of the vaccine, while Gardasil is only 50% effective at protecting against other cancer-causing HPV types.
As with any vaccine, it is important to consider the vaccine’s safety and potential side effects. The safety of the HPV vaccine was studied in clinical trials before it was licensed. For Gardasil, over 29,000 males and females participated in the trials, while Cervarix studied over 30,000 females from around the world.
In addition to clinical trials, safety information is available through the Vaccine Adverse Event Reporting System (VAERS). As of September 30, 2010, of the 32 million doses of Gardarsil that have been distributed in the U.S., 17,160 adverse events have been reported. Of these reports, 92% were considered non-serious, which includes fainting, pain and swelling at the injection site, headache, nausea, and fever. It should be noted that fainting is common following most injections and vaccinations. In addition, 8% of the reported events were considered serious. All of these serious reports have been carefully reviewed by medical experts and no common medical problems caused by the vaccine were found. However, there have been some reports of individuals getting blood clots after receiving the vaccine, although these individuals had other blood clot risk factors such as using birth control pills, smoking, and obesity. As of September 30, 2010, there have been 56 U.S. reports of death among females who have received the Gardasil vaccine, with 30 of the reports confirmed. Of the confirmed reports, there was no unusual pattern to suggest that the deaths were caused by the vaccine.
In spite of this finding, there has been some concern about a link between Gardasil and a rare nervous system disorder known as Guillain-Barré syndrome (GBS). In a 2010 study in Vaccine, Nizar Souayah and co-authors looked at the VAERS database between June 2006 and September 2009 and compared the occurrence of Guillain-Barré syndrome after vaccination with Gardasil to the occurrence after vaccination with Menactra and influenza. The researchers concluded that the average weekly reporting rate of GBS for the six weeks after vaccination was 6.6 events per week per 10 million subjects, which is double what it was for Menactra (also administered to children 11 and up), and about five times the weekly reporting rate for flu vaccine. When limited to the first two weeks after vaccination, the average weekly reporting rate of GBS jumped to 14.5 cases per week per 10 million subjects vaccinated with Gardasil as compared to 5.7 cases among subjects vaccinated with Menactra.
Three CDC researchers have criticized Souayah’s study, pointing out that the VAERS database has numerous shortcomings and that the authors used as their denominator the number of doses distributed, divided by 3, even though not everyone receives all three doses. They also maintain that being a new vaccine, adverse reactions to Gardasil were over-reported.
There are, in fact, problems with VAERS-it is a passive system-but usually the problem is under-reporting. Most parents don’t know how to report problems or don’t find the time to do so, and many doctors under-report as well. If there was extensive under-reporting of problems associated with Gardasil, then that may have partly offset Sourayah’s overestimation of the number of people getting all 3 doses. Clearly, more research will need to be done to determine if Gardasil slightly increases the very low risk of GBS.
Cervarix has only been linked to 3 adverse event reports so far. This low number is due to the fact that the vaccine was only recently approved in the U.S., and relatively few individuals have received it so far.
On June 29, 2006, the CDC Advisory Committee on Immunization Practices (ACIP) recommended that Gardasil be given routinely to all 11-12 year old girls. The recommendation was based on less than two years of efficacy, safety and immunogenicity data provided to the FDA from clinical trials with 16-23 year-olds, combined with safety and immunity studies in 9-15 year old girls. In October of 2009, the CDC’s ACIP also recommended Cervarix for 11-12 year old girls, but this too was based on short-term data. However, Cervarix’s approval was based on several studies where subjects were followed for an average of 3 to 7.5 years-a longer period than the Gardasil studies, but still not long enough to know the longer-term effects of the vaccine.
If the goal is to prevent cervical cancer in females, either Cervarix or Gardasil may be used, said the committee, which further noted that one vaccine could be substituted for the other, if needed, to complete the three-dose series.
Who should get it? Who should not?
The data that Merck presented to the FDA in 2006 indicated that Gardasil would not be effective against strains of HPV that the women were currently infected with at the time of vaccination. This finding has often been misunderstood. What it means is that the vaccine will not treat existing infections. However, data show that having a previous HPV infection that has cleared by the time you get the vaccine will not interfere with the vaccine’s effectiveness. But, if you have an ACTIVE infection that has not cleared, the vaccine will not be as effective against that type of HPV in the future.
At what Age is it Most Effective?
Because HPV exposure may occur even in the first 10 years of life through non-sexual skin-to-skin contact, or while being born, there is no age at which the vaccine will always be effective for everyone. According to the Centers for Disease Control (CDC), “the best way a person can be sure to get the most benefit from HPV vaccination is to complete all three doses before beginning sexual activity.” While researchers still do not understand or agree on the level of antibody titers necessary to have protection from HPV, there are data to indicate that most teenagers and women who are vaccinated after being previously exposed to HPV have even more antibodies than those who are vaccinated before they become sexually active.
So, is it a good idea to vaccinate girls as young as 12? It is difficult to answer that question because we don’t know how long the vaccines last. A few years from now, the vaccine manufacturers may announce that booster shots are needed. If that’s the case, will young adults who were vaccinated as children actually get them? What if the booster is expensive and they don’t have coverage for it?
In spite of these unknowns, several states are considering laws requiring HPV vaccines for school attendance. In Virginia and Washington, D.C., for example, all girls entering sixth grade in the fall of 2009 were required to be vaccinated against HPV unless a parent specifically requested a waiver. While the vaccine may be safe for girls as young as 12, we do not yet have enough data on how effective it is or how long it lasts to justify this policy, particularly given the high cost of the vaccine to working class and middle class parents and to government health programs for the poor. The vaccine’s safety and antibody response was tested on girls as young as 9 and 10, but the impact on lesions or disease was not studied in girls under 16. Since data show that the antibodies protecting vaccinated girls and women against HPV 18, a major cause of cervical cancer, appear to decrease over time, many girls vaccinated at age 12 could possibly lose much of their immunity against HPV 18 just as they are becoming more sexually active at ages 16 or 17.
As with any sexually transmitted disease, all it takes is exposure to one infected partner to acquire HPV. The chances of HPV and cervical cancer increase with the number of sexual partners, and the number of sexual partners of their sexual partners. Research is now underway to evaluate the effectiveness of Gardasil among women 27 to 45, and also in boys and men.
To view statements and testimony on NCHR’s opinions and recommendations for the HPV vaccine, visit http://www.center4research.org/2009/04/testimony-of-dr-diana-zuckerman-before-dc-health-committee-on-hpv/ or http://dev.stopcancerfund.org/p-cervical-cancer-hpv/hpv-q-a/
How Do I Get an HPV Vaccine?
The retail price of the vaccine is about $125 per dose (or $375 for full series), but most large insurers cover the costs of the vaccine, which may be administered by your doctor.
It is estimated that 85-89% of children with health insurance are covered for the HPV vaccine and other routine vaccinations.[13,14,15] The CDC Committee has also recommended that the HPV vaccine be included in the Vaccines for Children (VFC) Program, the federal program which provides free vaccinations to children 18 years of age and under who are uninsured, on Medicaid, protected by the Indian Health Services Act, or underinsured. Children enrolled in the VFC program receive the vaccine free of charge. Approximately 41% of all childhood vaccines in the United States are purchased by and administered through the VFC Program. However, the CDC recommendation does not include a booster shot, and even if it did, once girls are older than 18 years, the VFC Program would not cover the cost of the HPV vaccine or a booster.
Additional details regarding the Vaccines for Children Program, including what it is, who is eligible, what it covers, and how to enroll, may be found at http://www.center4research.org/vaccines-children-program-vfc/
The Great Debate: Is it Worth it?
There are certainly both benefits and drawbacks for the HPV vaccine, with some people benefiting more than others. From a broad perspective, the vaccine may not be cost effective because long-term effectiveness is unknown and we don’t yet know if booster shots are necessary to sustain protection against the virus. According to a modeling analysis done by Ruanne Barnabas, a cervical cancer vaccine must last at least 15 years in order to prevent cancer and not just postpone it.
Getting regular Pap smears and screenings and limiting your number of sexual partners are effective strategies whether you are vaccinated or not, so spending money on Pap smears may be the most economical way to protect women against HPV and cervical cancer. However, for women who are less likely to undergo regular Pap smears, and especially for women at highest risk for getting HPV and cervical cancer (such as Hispanics and blacks), the HPV vaccine reduces risk.
Who’s Getting Vaccinated?
According to the CDC, in the general U.S. population of adolescents 13 to 17 years old, 37% have received at least one dose of the three-dose vaccination and 18% have received all three doses of the vaccination, as of 2008. Given that the vaccination was relatively new at the time of data collection, it’s safe to assume that these rates have increased over the past two years. Also, as of 2008, 42% of adolescents living at or above poverty received at least one dose of the vaccine, with 36% receiving all three doses. In comparison, for those living below poverty, 41% have received at least one dose of the vaccine, while 46% have received all three doses of the vaccine. Girls and women living below poverty were fully vaccinated at a higher rate than those living at or above poverty. When looking at coverage by race/ethnicity, 35% of white adolescents have been covered by the vaccine, in comparison to 36% of blacks, 44% of Hispanics, 53% of American Indian/Alaska Natives, and 41% of Asians. High rates of coverage among those at or below poverty level, and among American Indian/Alaska Natives, can be partly explained by the VFC program (see our article “The Vaccines for Children Program (VFC)”).
Effect of Vaccine and VFC on Racial and Social Differences in HPV and Cervical Cancer Rates
Because the HPV vaccination is provided under VFC, this may eventually reduce differences in HPV and cervical cancer rates by protecting the most at-risk individuals against the four primary HPV types. When looking at racial statistics about who is getting the vaccine, Hispanics and American Indians/Alaska Natives are receiving the vaccine at much higher rates than whites and blacks. Because Hispanics have higher rates of cervical cancer in comparison to whites and blacks, the VCF Program could narrow this gap. The VFC Program can reach out to the medically underserved, who are less likely to receive regular cancer-prevention screenings. Assuming that the vaccine is effective in the long-run (which is still unknown), the VFC program could potentially prevent 70% of HPV cases in those who are vaccinated. As a result, expensive follow-ups to abnormal pap smears may also be avoided. However, even with the vaccine, it is still very important to get regular pap smears to stay healthy and prevent cervical cancer.
The Bottom Line
Like any public health strategy, a vaccine’s risks must be weighed against its benefits. That is why it is so important to determine how effective the vaccine is against preventing HPV and cervical cancer, and for how long. If the vaccine is offering less protection than it promises or is wearing off by the time most girls are becoming sexually active, then some people may decide that the cost and risks of the vaccine simply aren’t worth it. It’s important to remember that whatever you decide, you still need to get regular Pap smears. But for women who can’t or don’t get annual Pap smears and who can get the HPV vaccine at low or no cost through their insurance or through the VFC Program, the HPV vaccines (Gardasil or Cervarix) provide needed protection.
- Centers for Disease Control and Prevention (CDC) (2009) Genital HPV Infection Fact Sheet. Retrieved from http://www.cdc.gov/STD/HPV/STDFact-HPV.htm.
- Cullins M. (2009) HPV: Planned Parenthood. Retrieved from http://www.plannedparenthood.org/health-topics/stds-hiv-safer-sex/hpv-4272.htm.
- Schiffman M and Castle PE (2003 Aug.) Human papillomavirus: epidemiology and public health. Archives of Pathology and Laboratory Medicine 127(8):930-934. Retrieved from (PMID 12873163) http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=127&page=930.
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- American College of Obstetricians and Gynecologists (20 Nov. 2009). First Cervical Cancer Screening Delayed Until Age 21– Less Frequent Pap Tests Recommended. Retrieved from http://www.acog.org/from_home/publications/press_releases/nr11-20-09.cfm.
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- Centers for Disease Control and Prevention (CDC) (2010 May 21). Reports of Health Concerns Following HPV Vaccination. Retrieved from http://www.cdc.gov/vaccinesafety/vaccines/hpv/gardasil.html.
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- Clinical Review of Biologics License Application for Human Papillomvirus 6,11,16,18 L1 Virus Like Particle Vaccine (S. cerevisiae) (STN 125126 GARDASIL), manufactured by Merck, Inc. (2006). Accessed on March 23, 2009, U.S. Food and Drug Administration Web site: http://www.fda.gov/cber/review/hpvmer060806r.pdf.
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