Corinna Kaarlela, News Director
Source: Kristen Bole
kbole@pubaff.ucsf.edu
415-476-2557

10 May 2007


Karen Smith-McCune, MD
UCSF experts cautious about vaccine for cervical cancer virus

Unknowns about the effectiveness and safety of the new human papillomavirus (HPV) vaccine demand thoughtful deliberation by clinicians on its role in cervical cancer prevention, according to two UCSF women’s health specialists.

The lack of long-term follow-up to assess vaccine efficacy and safety, as well as the lack of testing in the age group targeted for the vaccine (11 to 12 year-old girls), are among the main reasons for such caution, they say.

Their analysis is reported in today’s issue (May 10, 2007) of the “New England Journal of Medicine,” which focuses on the new vaccine. The editorial and other NEJM articles are available online at http://content.nejm.org.

The vaccine, which has received international attention since its approval by the Food and Drug Administration last June, targets four HPV types, two of which can cause cervical cancer, according to George F. Sawaya, MD, and Karen Smith-McCune, MD, who are co-authors of the editorial and are associate professors in the UCSF Department of Obstetrics, Gynecology and Reproductive Services.

Previously published data about the vaccine have indicated 100 percent effectiveness against the pre-cancerous cervical lesions that are associated with the HPV types targeted by the vaccine. That data applied to women who had not previously been exposed to those viral types. New studies reported in this issue of the NEJM confirm these positive findings, but also provide information about the impact of vaccination in a larger, more representative population of all trial participants, the UCSF co-authors say. The new data cover all participants regardless of prior HPV exposure and all pre-cancerous lesions, regardless of HPV type.

“These new studies provide a preliminary glimpse of what we might expect from vaccinating women up to age 26 who have already been sexually active, as is recommended by the Centers for Disease Control and Prevention,” Sawaya says.

The overall efficacy of the vaccine for reducing pre-cancerous cervical lesions from any HPV type was modest: over 3 years, 3.6 percent of vaccinated women received this diagnosis compared to 4.4 percent of unvaccinated women. Rates of the most severe lesions were not significantly reduced by vaccination, the co-authors say.

“There has been an understandably positive response to the promise of this vaccine, but we have to balance that promise with what is actually known,” says Smith-McCune, who has chosen not to vaccinate her own teenage daughters against HPV at this time.

“The issue here is not whether we want to protect women against cervical cancer, but the safety and efficacy of this specific vaccine,” Smith-McCune says. “One of the largest questions is whether targeting only two of at least 15 HPV types known to cause cervical cancer is enough to impact development of cervical pre-cancer and cancer.”

An estimated 9,700 American women were diagnosed with cervical cancer in 2006, according to the American Cancer Society. The vast majority of those cancers can be avoided with regular cervical cancer screening with the Pap test, the authors say.

“The Pap test is a proven and effective way to reduce cervical cancer risk, whereas we are just beginning to find out about the overall effectiveness and safety of the vaccine,” Smith-McCune says.

“So far, the HPV vaccine looks promising,” says Sawaya. “The diagnosis of a rare cancer usually related to HPV in one woman who received the vaccine, however, gives us pause and argues for a cautious approach until the current studies are completed and final outcomes reported.”

Both stressed that since screening is widely available, cervical cancer is not a public health emergency in this country.

“The rush toward mandatory vaccination is puzzling, but it is important to realize that the major studies are on-going,” Sawaya says. “As with any preventive measure, we need to be quite certain that the benefits of vaccination outweigh the harms before we embark on widespread vaccination programs.”

Both doctors urged women to continue to receive regular cervical cancer screening, regardless of whether they have received the vaccine.

UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.

###

Additional information:

Part 1

First Appeared Wednesday, 20 September '06

UCSF Panel Discussion Airs Concerns, Hopes for New HPV Vaccines Part 1 of 2

http://pub.ucsf.edu/today/cache/news/200609198.html

Part 2

UCSF Panel Discussion Airs Concerns, Hopes for New HPV Vaccines Part 2 of 2

http://pub.ucsf.edu/today/cache/news/2006092010.html

http://pub.ucsf.edu/newsservices/releases/200705103/



Volume 356:1905-1908 May 10, 2007 Number 19
Next



Politics, Parents, and Prophylaxis — Mandating HPV Vaccination in the United States

R. Alta Charo, J.D.


Cancer prevention has fallen victim to the culture wars. Throughout the United States, state legislatures are scrambling to respond to the availability of Merck's human papillomavirus (HPV) vaccine, Gardasil, and to the likely introduction of GlaxoSmithKline's not-yet-approved HPV vaccine, Cervarix, which have been shown to be effective in preventing infection with HPV strains that cause about 70% of cases of cervical cancer. At the Centers for Disease Control and Prevention (CDC), the Advisory Committee on Immunization Practices (ACIP) has voted unanimously to recommend that girls 11 and 12 years of age receive the vaccine, and the CDC has added Gardasil to its Vaccines for Children Program, which provides free immunizations to impoverished or underserved children.

Yet despite this federal imprimatur, access to these vaccines has already become more a political than a public health question. Though the more important focus might be on the high cost of the vaccines — a cost that poses a genuine obstacle to patients, physicians, and insurers — concern has focused instead on a purported interference in family life and sexual mores. This concern has resulted in a variety of political efforts to forestall the creation of a mandated vaccination program. In Florida and Georgia, for example, efforts to increase adoption of the vaccine have been stalled by legislative maneuvering. The Democratic governor of New Mexico has announced that he will veto a bill that mandates vaccinations. And the Republican governor of Texas came under fire (and under legal attack from his own attorney general) when he issued an executive order to the same effect, mandating that all girls entering the sixth grade receive the vaccine; the policy was attacked as an intrusion on parental discretion and an invitation to teenage promiscuity. But all these measures included a parental right to opt out, whether on religious or secular grounds. The opposition seemed more about acknowledging the realities of teenage sexuality than about the privacy and autonomy of the nuclear family.

For more than a century, it has been settled law that states may require people to be vaccinated, and both federal and state court decisions have consistently upheld vaccination mandates for children, even to the extent of denying unvaccinated children access to the public schools. State requirements vary as to the range of communicable diseases but are often based on ACIP recommendations. School-based immunization requirements represent a key impetus for widespread vaccination of children and adolescents1 and are enforceable even when they allegedly conflict with personal or religious beliefs.2 In practice, however, these requirements usually feature exceptions that include individual medical, religious, and philosophical objections.



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State Laws and Proposed Legislation Mandating HPV Vaccination.
All legislation mandating HPV vaccination includes some form of parental opt-out. The Texas mandate is the result of an executive order from the governor, and its legality is being challenged by the attorney general of Texas. There is also legislation under consideration in Texas that would prohibit a mandate. If passed, it would override the executive order. The Virginia law was passed by the legislature and signed by the governor. The New Mexico legislation was passed by the House and Senate and was then vetoed by the governor. Bills in California and Maryland have been withdrawn for consideration, and the bill in South Carolina has been tabled. Neither Alaska nor Hawaii has considered a mandate. Legislation that makes provisions for funding is under consideration in many states but is not shown here. The various bills would require insurance companies to cover vaccination, allocate state funds, direct agencies to apply for federal funds, or some combination. Information is from the National Conference of State Legislatures and is accurate as of April 27, 2007.




HPV-vaccination mandates, which are aimed more at protecting the vaccinee than at achieving herd immunity, have been attacked as an unwarranted intrusion on individual and parental rights. The constitutionality of vaccination mandates is premised on the reasonableness of the risk–benefit balance, the degree of intrusion on personal autonomy, and, most crucial, the presence of a public health necessity. On the one hand, to the extent that required HPV vaccination is an example of state paternalism rather than community protection, mandatory programs lose some of their justification. On the other hand, the parental option to refuse vaccination without interfering in the child's right to attend school alters this balance. Here the mandates act less as state imperatives and more as subtle tools to encourage vaccination. Whereas an opt-in program requires an affirmative effort by a parent, and thus misses many children whose parents forget to opt in, an opt-out approach increases vaccination rates among children whose parents have no real objection to the program while perfectly preserving parental autonomy.

Opposition to HPV vaccination represents another chapter in the history of resistance to vaccination and, on some levels, reflects a growing trend toward parental refusal of a variety of vaccines based on the (erroneous) perception that many vaccines are more risky than the diseases they prevent. In most cases, pediatricians have largely restricted themselves to educating and counseling objecting families, since it is rare that the risks posed by going unvaccinated are so substantial that refusal is tantamount to medical neglect. In the case of HPV vaccine, parents' beliefs that their children will remain abstinent (and therefore uninfected) until marriage render it even more difficult to make the case for mandating a medical form of prevention. Even with an opt-out program, critics may argue that the availability of a simple and safe alternative — that is, abstinence — undermines the argument for a state initiative that encourages vaccination through mandates coupled with an option for parental refusal.

But experience shows that abstinence-only approaches to sex education do not delay the age of sexual initiation, nor do they decrease the number of sexual encounters.3 According to the CDC, though only 13% of American girls are sexually experienced by 15 years of age, by 17 the proportion grows to 43%, and by 19 to 70%.4 School-based programs are crucial for reaching those at highest risk of contracting sexually transmitted diseases, and despite the relatively low rate of sexual activity before age 15, the programs need to begin with children as young as 12 years: the rates at which adolescents drop out of school begin to increase at 13 years of age,1 and younger dropouts have been shown to be especially likely to engage in earlier or riskier sexual activity.

Another fear among those who oppose mandatory HPV vaccination is that it will have a disinhibiting effect and thus encourage sexual activity among teens who might otherwise have remained abstinent. This outcome, however, seems quite unlikely. The threat of pregnancy or even AIDS is far more immediate than the threat of cancer, but sex education and distribution of condoms have not been shown to increase sexual activity. Indeed, according to a study conducted by researchers at the University of Pennsylvania, it is the comprehensive sex-education approaches that include contraceptive training that "delay initiation of sexual intercourse, reduce frequency of sex, reduce frequency of unprotected sex, and reduce the number of sexual partners."5 Opposition to the HPV-vaccination mandates, then, would seem to be based more on an inchoate concern: that to recognize the reality of teenage sexual activity is implicitly to endorse it.

Public health officials may have legitimate questions about the merits of HPV vaccine mandates, in light of the financial and logistic burdens these may impose on families and schools, and also may be uncertain about adverse-event rates in mass-scale programs. But given that the moral objections to requiring HPV vaccination are largely emotional, this source of resistance to mandates is difficult to justify. Since, without exception, the proposed laws permit parents to refuse to have their daughters vaccinated, the only valid objection is that parents must actively manifest such refusal. Such a slight burden on parents can hardly justify backing away from the most effective means of protecting a generation of women, and in particular, poor and disadvantaged women, from the scourge of cervical cancer. To lighten that burden even further, the governor of Virginia has proposed that refusals need not even be put in writing. Perhaps it is time for parents who object to HPV vaccinations to take a lesson from their children and heed the words of Nancy Reagan: Just say no.



Source Information

Professor Charo is a professor of law and bioethics at the University of Wisconsin, Madison.

An interview with Professor Charo can be heard at www.nejm.org.

References
http://content.nejm.org/cgi/content/full/356/19/1905


http://content.nejm.org/


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