In the ongoing war on cancer, the new human papillomavirus (HPV) vaccine has been hailed as a breakthrough. “This is a watershed event,” proclaimed American Cancer Society president Carolyn Runowicz — an event “we hope will help usher in a new era of cancer prevention.”
The vaccine, Merck’s Gardasil, was approved by the FDA in June and should be commercially available this summer or autumn. It targets four strains of HPV: HPV-16 and HPV-18, which account for 70% of all cases of cervical cancer, and HPV-6 and HPV-11, which are responsible for about 90% of genital wart cases. The vaccine is administered in three shots over six months at a cost of $360 for all three doses.
Cervarix, a rival cervical cancer vaccine produced by GlaxoSmithKline, was filed for approval in Europe in March 2006, with submission to the FDA expected by the end of the year. Cervarix targets HPV-16 and HPV-18.
To find out what the introduction of the new vaccine will mean for your practice, Nelly Edmondson Gupta, senior editor for Cortlandt Forum, a sister publication to The Clinical Advisor, spoke with two experts: Kevin Ault, MD, associate professor of gynecology and obstetrics at the Emory University School of Medicine in Atlanta, and Jonathan Temte, MD, PhD, associate professor of family medicine at the University of Wisconsin-Madison School of Medicine and Public Health. Dr. Ault has been a clinical investigator on several HPV vaccine trials, including those for Gardasil, and Dr. Temte serves as liaison to the CDC’s advisory committee on immunization practices for the American Academy of Family Physicians. Here’s what they had to say.
Q: Which patients will be good candidates?
Dr. Temte: The vaccine is approved for females aged 9-26. Ideally, we want to give this vaccine to girls when they are 11 or 12 years old. This is also an excellent time to administer the diphtheria, pertussis, and tetanus booster (Tdap) and the meningococcal conjugate (MCV4) vaccines. So we’re looking at this as an important preventive-health visit at a crucial age — a chance to provide three excellent vaccines and, at the same time, talk about lifestyle issues, such as diet and exercise, as well as offer counseling about risky behaviors (cigarette smoking, drug and alcohol use, and sexual activity).
Dr. Ault: The FDA advisory committee set a broad age range for this vaccine, and younger and older groups will benefit in different ways. The younger group will generally not yet be sexually active, but they can produce lots of antibodies to the virus. The older group will have more interest in reproductive health and will benefit more directly and immediately from a decreased risk of abnormal Pap tests and genital warts.
Q: Should the new vaccine be given to males?
Dr. Temte: The vaccine will prevent genital warts in both sexes, and there is certainly some benefit to males receiving it. However, males are not included in the current licensure application, and you will not see a recommendation coming out for males at this time. One problem is that once use of the vaccine is widespread in females, broadening the recommendation to include males may be prohibitively expensive. However, I suspect there will be ongoing discussion regarding a male indication later on.
Q: If a woman is already infected with HPV when she receives the vaccine, will it still prevent cervical cancer?
Dr. Temte: These vaccines only prevent infection. They do not prevent disease in a person who is already infected with the virus. HPV is a family of related viruses with a number of serotypes. This vaccine offers protection against the two types that are responsible for most cervical cancers. In some trials, the manufacturer did a lot of testing before immunization to find out whether subjects had been exposed to any of the viruses. If a woman has been exposed to one type of HPV, the vaccine will not have much effect on that serotype, but it will still offer protection against the three other types. If a woman has been infected with all four types, the vaccine would do her little good. But such situations are so rare that there will be no recommendation to test for the virus prior to administering the vaccine. In order to get maximal benefit from the vaccine, however, the series should be started prior to a patient’s sexual debut.
Q: Will the vaccine eliminate the need for Pap tests?
Dr. Ault: No. There are 20-30 types of genital-tract HPV that can cause problems. The four types in the new vaccine are responsible for most cervical cancers; unfortunately, cervical cancer can also be induced by a number of other serotypes. The vaccine is used to prevent disease, and the Pap test is used to find it.
Dr. Temte: For the time being, current recommendations regarding Pap testing will remain. The recommendation is for an annual Pap test in women who are sexually active until they’re in a monogamous relationship and have three consecutive normal test results. Most clinicians drop back in frequency thereafter because the likelihood of viral acquisition is greatly reduced. As the vaccine comes into greater use, authorities may modify Pap test recommendations based on what occurs empirically. However, for now I caution people to think of this vaccine as a means to prevent cervical cancer rather than as a reason to eliminate screening.
Q: Does the vaccine cause side effects?
Dr. Ault: Of patients who have side effects, 90% have local-site arm soreness, and 50% have headaches. Most headaches are transient, and there were an equal number of headaches in the treatment and placebo groups. Severe reactions are uncommon.
Q: What should clinicians tell sexually active women over age 26 who want the vaccine?
Dr. Ault: At this point, we have data only for patients aged 26 and younger. There may be less benefit for older women because more of them will already have been exposed to the virus. We are now looking for data in older women.
Q: Are there any contraindications to administering the new vaccine?
Dr. Ault: In one subgroup of test subjects, researchers did find a slightly increased risk of birth defects in women who had unknowingly conceived prior to receiving the vaccine. So, as with any new drug, the vaccine probably should not be given to pregnant women.
Q: Although the advisory panel recommended the FDA approve the vaccine, members did have some concerns. What were they?
Dr. Ault: One concern is that once we eliminate some of the cancer-causing serotypes, they’ll be replaced by others. That’s always a concern when a vaccine is introduced; not all of the disease-causing viruses are in the vaccine.
Q: Could the HPV vaccine lead to sexual promiscuity?
Dr. Ault: I hope not. But that question could be a wonderful way to start a discussion with teenagers about the vaccine. If you ask teens why they’re not sexually active, they usually say it’s against their moral beliefs or because they’re afraid of getting pregnant. Sexually transmitted diseases (STDs) are farther down on their list of concerns, so it seems to me, as a parent and as a doctor, that talking about the vaccine could provide a good “teaching moment” to discuss STDs. Also, the vaccine won’t prevent many other things, such as HIV infection and unplanned pregnancy, which can also happen as a result of promiscuity.
Dr. Temte: There is virtually no evidence that the vaccine could lead to promiscuity. One could argue that telling children to wear helmets might cause them to ride bicycles in risky ways, and we haven’t seen that happen.
Q: What clinical-management problems could the vaccine cause?
Dr. Ault: Some clinicians are generally not good vaccinators, so they will need someone in the office who can administer the vaccine after the patient has been counseled. Clinicians will also need to have the right equipment to offer vaccinations, such as storage refrigerators.
Dr. Temte: Because this is a three-dose vaccine, it will be important to keep careful records and provide reminders to efficiently get patients into the office for all three doses. There are also issues around reimbursement for those without private coverage for the vaccine. Vaccines that are recommended universally for children younger than age 18 will be covered under the Vaccines for Children program. To qualify for this program, patients have to meet federal poverty guidelines. Beyond that, most states have federal funding to provide vaccines to people who fall through the cracks, such as the working poor who do not qualify for federal assistance and uninsured people who are making too much money to qualify for assistance.
One potential problem is that there can be a delay of six to nine months between the time vaccines are recommended and the time they actually become official recommendations. I suspect some insurers and HMOs will cover this vaccine right away and others will hold off until the recommendation is official. The bottom line is that a lot of us are going to have to say to our patients, “We’d like to give this to you. Call your insurer or HMO and see if it’s covered.” The CDC and the national immunization program have a Web site with provisional recommendations; go to www.cdc.gov/nip and click on Status of Licensure and Recommendations for New Vaccines.
Q: Should clinicians tell patients about the new vaccine?
Dr. Temte: Yes. I think it is appropriate to be on the leading edge of the information curve. There have already been ads in various publications about the vaccine, and many patients are aware of it. This vaccine will receive almost unprecedented interest from patients and parent groups; there will be a huge demand for it. This is is a very significant intervention in women’s health.
Q: Should clinicians encourage parents to get their children vaccinated?
Dr. Ault: Yes, parents will have to be involved because they must give consent. Most lay people don’t make the connection between HPV and cancer; many have never even heard of HPV. So people need basic education about HPV and cancer, and they need to know how common the virus is.