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The HPV vaccine has been a huge success story for the scientific, medical and public health communities. Over the past two decades we have gone from identifying that cervical cancer is caused by infection with the HPV virus to the development of a vaccine against certain HPV types to the widespread use and acceptance of the vaccine. This progression from basic science to clinical research to public health has occurred at a remarkable pace and set a new standard for medical discovery.
However, a number of recent articles have questioned whether we have been too quick to adopt the HPV vaccine and whether the benefits of vaccination have been oversold. In this blog article, we review some of the evidence and weigh the pros and cons of vaccination in two groups of women.
1. First some background:
- Cervical cancer was once the leading cause of cancer death in women in the United States. Since the advent of cervical cancer screening (e.g., Pap smears), deaths from cervical cancer have dropped 70 percent. Still 12,000 women are diagnosed with cervical cancer each year in the U.S. and 4,000 women die from the disease.
- Cervical cancer is caused by the HPV virus. There are over 100 types of HPV, only a subset of which causes cervical cancer (called high-risk types).
- HPV is transmitted through sexual intercourse. It is estimated that 70 percent of adults have been infected by HPV at some point in their lives. It infects both men and women.
- The vast majority of HPV infections resolve on their own without any symptoms or complications. We do not fully understand why the infection resolves in most cases and not others.
- The HPV vaccine protects against infection with 4 HPV types — 16, 18, 31, 33. HPV 16 and 18 are high-risk types and are associated with 70 percent of cervical cancers. The vaccine is made by Merck and is marketed as Gardasil.
- The current CDC recommendations are to routinely vaccinate girls ages 11 to 12 and to vaccinate girls and women ages 13 to 26 who have not yet been vaccinated. Women who receive the vaccine are advised to continue routine screening for cervical cancer (e.g. Pap smears).
2. Next we review the benefits and harms of vaccination, differentiating between what we are told and what the evidence says:
What we are told: The HPV vaccine protects against cervical cancer.
What the evidence says: There is no direct evidence that the HPV vaccine prevents cervical cancer. What studies have shown is that vaccination prevents infection with the 4 HPV types the vaccine protects against; it also prevents against cellular changes that sometimes develop in response to persistent infection with these HPV types. But no study has shown that the vaccine ultimately prevents cervical cancer. Part of the problem is that it takes 10 to 20 years from infection with HPV to the development of cervical cancer. In order to prove that the vaccine prevents cancer, a study that follows thousands of women for at least this many years would be required. Regardless, it is misleading to call Gardasil the cervical cancer vaccine.
What we are told: Getting the HPV vaccine will save your life.
What the evidence says: Cervical cancer screening (e.g. Pap smears) prevent almost all cases of cervical cancer. The few thousand cases per year of cervical cancer occur in women who have never had a Pap smear and receive them infrequently. Thus, even if we take as a given that the vaccine prevents cancer, the HPV vaccine will not prevent cancer and will not save lives in women who have access to medical care and get regular Pap smears. In women who get cervical cancer screening infrequently or do not have access to medical care (e.g., lower income and marginalized women in the U.S., women in developing countries) the vaccine may prevent cancer and save lives, but again there is no direct evidence to support this.
What we are told: The HPV vaccine is safe.
What the evidence says: From the available evidence, we know that the HPV vaccine carries risks similar to other vaccines. However, the term “safe” is relative. We tolerate the risks of surgery when we have appendicitis and consider it to be a “safe” procedure. But when undergoing elective surgery (e.g., cosmetic surgery) we demand higher levels of safety. A recent report in JAMA on the safety of the HPV vaccine found that fainting and pain at the site of injection are the most common side effects from vaccination. However, it also found that among 12,424 self-reported “events” from vaccine administration, 772 were “serious,” including 32 reports of death. The authors rightfully concluded that causality could not be established and that further research into these potential harms are warranted. But the bottom line is that we have a limited experience with the HPV vaccine and so many uncertainties about its safety remain.
3. Putting all this information together let’s look at risks and benefits of HPV vaccination for two types of women:
Women with access to medical care and routine Pap smears
Benefits:
- no decrease in cervical cancer or death from cervical cancer (as discussed above, cervical cancer is rare in women who get regular Pap smears)
- no decrease in Pap smears (regardless of vaccination, women are advised to undergo routine cervical cancer screening)
- potential reduction in follow up testing and invasive procedures (Pap smears may be less likely to be abnormal due to lower rates of HPV 16 and 18)
Risks:
- pain at injection site, fainting, unknown risk of serious side effects
- cost (in women without insurance the vaccine costs $100-$150 per dose times three doses)
Conclusion: The benefits and risks of HPV vaccination are uncertain. Some women may look at the balance of benefits and risks and decide to get vaccinated, while others may look at the same information and decide that the benefits of vaccination are not worth the risks.
Women with limited access to medical care:
Benefits:
- potential decrease in cervical cancer and death from cervical cancer
Risks:
- pain at injection site, fainting, unknown risk of serious side effects
- cost (in women without insurance the vaccine costs $100-$150 per dose times three doses)
Conclusion: In women with limited access to medical care, the balance of benefits and risks is more in favor of vaccination, although a great deal of uncertainty remains.
4. Here are some of the dangers of our current HPV vaccine strategy:
- We only have so many resources. Even if vaccination does prevent cervical cancer and even if the side effects are minor, we have to wonder if vaccinating women who already are at low-risk of cervical cancer because of access to effective screening is a wise use of limited resources.
- We are still missing high risk groups. Pre-HPV vaccine, cervical cancer predominantly affected marginalized, low-income women. Today, post-HPV vaccine, because we are primarily vaccinating women who already have access to health care or who can afford to pay for it out-of-pocket, the women who are most in need of vaccination and are most likely to benefit from it still face the same risk of cervical cancer.
- We may stop researching the HPV vaccine. The development and widespread acceptance of the HPV vaccine is in many ways the end of a long journey from basic science to translational research to public health. But in other ways, it’s just the beginning. There are many unanswered questions about the HPV vaccine including: a) does the vaccine ultimately prevent cervical cancer and death?, b) how long does immunity last and will booster doses be required?, and c) what are risks of vaccination? The fact that we are already administering the HPV vaccine should not deter us from answering these critical questions.
5. Final thoughts:
Despite limited evidence, I still support the HPV vaccine. If I were a woman, I would opt for vaccination, and as a physician, I generally counsel women to get vaccinated. My concern here is that the benefits and risks of vaccination have been overstated and that the decision to get vaccinated is not as obvious as Merck would have us believe. For most women, vaccination will not significantly alter their risk of cervical cancer. At the same time, the risks of vaccine administration are not well known. The decision then becomes a personal choice — one that requires a well-grounded understanding of what the vaccine is and what the vaccine isn’t.
Copyright Shantanu Nundy, M.D.
If you enjoyed this post, please visit Dr. Nundy's web site BeyondApples or read his book, Stay Healthy At Every Age.
References:
JAMA article on safety of HPV vaccine: http://jama.ama-assn.org/cgi/content/full/302/7/750?home
JAMA editorial on risks and benefits of vaccine: http://jama.ama-assn.org/cgi/content/full/302/7/795?home
JAMA article on marketing of HPV vaccine: http://jama.ama-assn.org/cgi/content/full/302/7/781?home
NY Times article on risks and benefits of vaccine:http://www.nytimes.com/2009/08/19/health/research/19vaccine.html?_r=1
NEJM article on HPV vaccine: http://content.nejm.org/cgi/content/full/359/8/861?home
