If women were to choose to be vaccinated with Gardasil and forgo further Pap screening, the rate of cervical cancer in the United States would rise from 8 to 14 cases for every 100,000 women. If they were to choose Cervarix instead, with no further Pap screening, the rate would rise from 8 to 9.5 cases for every 100,000 women.
If women were to choose both HPV vaccination and continued Pap screening, the rate of cervical cancer still would not decline from its current level of 8 cases for every 100,000 women. Instead, the benefit would be that fewer women have abnormal Pap tests, and fewer women would need to be treated for CIN 2+ disease.
Women and physicians must understand these facts. A woman who chooses to be vaccinated may gain individual protection, but the overall rate of cervical cancer will not be affected.
Dr. Huh: Regardless of the HPV vaccine selected, we need to seriously rethink how we screen women in the United States. One could easily argue that the combination of the vaccine and continued screening is too expensive. It might be wise to consider lengthening the screening interval—and, perhaps, further delaying initial screening to 25 years of age—to make cervical cancer prevention with both modalities more cost-effective.24 The most important thing to recognize is that women still need to be screened, even if they have been vaccinated.
As more women are vaccinated, we expect to see a decline in the prevalence of CIN 2+ and CIN 3+ lesions, and this will ultimately weaken the positive predictive value of cytology. Perhaps it is time to consider the HPV test as a primary screen, with triage to cytology in women who test HPV-positive.25
Dr. Smith-McCune: As we accumulate data over time about the effects of vaccination on the rates of CIN 3 and cancer, modeling will be helpful in determining the best screening algorithm for women who have been vaccinated against HPV.
It is important to remember that approximately 50% of women who are given a diagnosis of cervical cancer in the United States have never been screened. It is vital that we continue to reach out to the under-screened population and focus vaccination efforts on populations of girls who are likely to have limited access to care in the future.
7. Can we vaccinate every woman?
Dr. Lonky: Is universal vaccination of women achievable for either vaccine?
Dr. Felix: Universal vaccination against HPV would be achievable only via school mandates. Without them, vaccination will not approach the 80% threshold needed to produce herd immunity.
Despite the clear benefit of such mandates to the general population—particularly the medically under-served—the issue has become a political football. As a result, school mandates will probably never be realized.
Dr. Harper: I don’t believe it is ethical to mandate vaccination of all girls and women. It is a choice that women and parents, in conversation with their physicians and daughters, must make when considering how to be protected against cervical cancer. Herd immunity is a moot point because we are only vaccinating girls (50% of the population) and can never reach the theoretical 70% threshold for herd immunity to be apparent.
Dr. Lonky: Is the availability of two vaccines a boon or a hindrance?
Dr. Smith-McCune: I think it is always a good thing to have choices in medicine.
Dr. Huh: I see the availability of two vaccines as a boon. That availability means that two companies are now putting forth consistent educational messages about the importance of vaccination and, I hope, stimulating competition that will reduce the overall cost of the vaccine series. Having two vaccines can only promote awareness, access, and greater appreciation of the considerable protection these two vaccines provide.
I discern 8 barriers to HPV vaccination
Despite solid evidence that the quadrivalent (Gardasil) HPV vaccine and the bivalent (Cervarix) HPV vaccine protect against cervical cancer, only about one fifth of the female population between 11 and 26 years of age has received the full series of Gardasil since it won FDA approval in 2006. Barriers to vaccination are not financial alone, as the vaccination rate is similarly low among women who have health insurance.
Why isn’t the vaccination rate higher? I see eight barriers to full implementation:
- Economic disparities. Each vaccine costs roughly $400 (national average) for the full series of injections. Although women who do not get Pap screening are most likely to benefit from the vaccines, they usually cannot afford them. federal childhood immunization programs cover teens and young women until 18 years of age in most states, and until 21 years in a few. that leaves most women who seek vaccination from gynecologists without coverage.
- Fear. Pain at the injection site, syncope, and a slightly elevated incidence of thromboembolism are the adverse events most commonly associated with HPV vaccination in the literature. In the life cycle of a vaccine, reports of sudden death or neurologic injury (Guillain-Barré syndrome) occur in the early years, but are reported at a rate lower than 2 cases in every 10,000 women. Nevertheless, such events may create fear about undergoing immunization.
- Long latency period. Because the outcome of cancer prevention won’t become apparent for 20 to 40 years following vaccination, the need for immunization may seem less than urgent.
- Cultural and religious beliefs. Because carcinogenic HPV strains are sexually transmitted, some families may associate vaccination with the promotion of sexual activity. Even in states that mandate vaccination, the courts have upheld a parent’s right to refuse vaccination on these grounds.
- The premarket push. Aggressive promotion of vaccination by both manufacturers and a push by advocates for legislation to mandate the vaccine prior to completion of Phase-3 trials and gathering of robust safety data may have diminished trust in the vaccine and reduced its acceptance.
- Lack of legislation. In states that do not consider HPV vaccination to be a necessary public health intervention, the lack of mandates and funding reduce the vaccination rate. In addition, some legislators have been more active advocates of vaccination than others.
- Reduced involvement of the obGyn. ObGyns don’t routinely vaccinate patients; pediatricians do. Young women are slipping through the cracks because the conventional ObGyn practice does not have a vaccination program that ensures payment, reimbursement, and completion of the vaccine series. Many ObGyn practices are reluctant to institute such a program because the profit margin is small, there are associated risks, and the time required to counsel the patient and for follow-up is extensive.
- Failure to complete the series. Some women do not complete the full vaccine series, owing to cost or side effects, or both. Solid evidence that a single dose could be as protective as the full series would be compelling. A single-dose vaccine would also be less expensive.
The principal danger of a low vaccination rate is the loss of insurance coverage for immunization against HPV. On one hand, payers may begin to ask whether coverage is justified when so few girls and women are vaccinated, leaving the payer with two burdens: the expense of vaccination and the expense of conventional screening programs and treatment, although the costs of treatment would be reduced with vaccination. On the other hand, Gardasil’s protection against genital warts may provide incentive for payers to cover or discount the vaccine because of the reduction in the need to diagnose, triage, and treat condyloma.
Ultimately, HPV vaccination may become another optional intervention that is paid for by the individual, despite evidence in girls and women that cervical cancer can be prevented.
—NEAL M. LONKY, MD, MPH