Ana Lita, Director of the IHEU-Appignani Center for Bioethics, spoke at the UN Department of Economic and Social Affairs, Division for the Advancement of Women on June 6, 2006. The meeting was chaired by Ms. Rachel Mayanja, UN Assistant Secretary General and Special Advisor to UN Secretary General Kofi Annan on Gender Issues and Women’s Advancement (OSAGI). Over 20 high-ranking UN officials attended the meeting.
The text of her paper, “New vaccines for cervical cancer and new controversies”, is available here. We also have photographs from the meeting.
New vaccines for cervical cancer and new controversies
Many people, across academic, governmental, and lay communities alike, are developing a deeper appreciation of the bonds between human well-being and the unrelenting pace of technological advance. The recent growth in biotechnology and its success in satisfying both medical needs and human desires have raised many new bioethical questions. Hundreds of years ago, when medical science could offer little more than bleeding, blistering and purging-when the leech represented the cutting edge of biotechnology-choices were few and controversy scarce. Today, however, such bioethical controversies are driven not only by the magnitude of technological change but also by the resurgence of conservative “religious values” as well as the increasing public awareness (not necessarily public understanding) of the biotechnologies themselves. While many such advancements offer new solutions to old problems (e.g. the growing cadre of pharmaceutical drugs for treatment of everything from depression to hypertension), they have also spawned new possibilities for remaking our own lives and families-even our own societies. Concomitantly, biotechnological advancements have called into question the adequacy of our traditional (and arguably fundamental) thinking about ourselves.
Today, the Universal Declaration of Human Rights and other international agreements help carve out, in various ways, the normative state of global ethics. Still, there are biomedical and scientific issues that, although they have been widely discussed, have not yet been appropriately addressed by persons well versed in both the science and the ethical theory involved.
Some well-publicized examples include the negotiating fair terms of international property that appropriately balance the interests of all stakeholders involved, understanding and slowing global brain drain that leaves developing world countries worse off at the expense of their rich counterparts, and the ongoing debate over embryonic stem cell technologies.
I will now focus on cervical cancer, a disease that kills only women, for which a promising new vaccine is about to enter the market. This disease does not kill anywhere near as many people as HIV/AIDS, maybe 300,000 women in the world a year, mostly in developing countries. But those deaths are unnecessary, and may now be reduced “IF” the vaccine is deployed and used by women, and that is where the ethical issues come in.
The challenge of cervical cancer in USA and worldwide:
What is cervical cancer?
Cervical cancer is cancer of the cervix, the lower portion of the uterus leading to the beginning portion of the vaginal canal. The cervix is the object of testing when a Pap smear is performed. A Pap smear, named after the Greek-born American physician George Papanicolaou, has revolutionized women’s health by detecting early, pathologic, microscopic changes in cervical cells. The Pap smear allows for ongoing monitoring of such cells, which are the precursors to cancer.
What makes the cells abnormal?
Surprisingly, a virus causes cervical cells to become abnormal and is the reason why they turn cancerous. This virus-called the human papilloma virus (HPV)-is thus the cause of cervical cancer (the German virologist Harold zur Hausen linked HPV with cervical cancer in 1975 but few paid attention to his theory. Improved detection of viral DNA in the early 1990s vindicated his work.) It should be noted that there are many types of HPV, and only a few types are sexually transmitted and are able to cause cervical cancer. In particular, HPV types 16 and 18 cause more than 70% of cervical cancer cases worldwide, while the other 30% of cases are due to less common HPV types (such as HPV-31, -33, -35, -39, -45,-51, -66).
Who gets cervical cancer?
First, it is impossible to develop cervical cancer without first being infected by HPV. Thus, if a woman is not infected with HPV, she will not develop cervical cancer.
Second–and this can be a point of confusion–not all women who are infected with HPV will develop cervical cancer. In the US, for example, 80% of all sexually active people have one or more HPV strains and about 20 million people are infected at any given time. However, because of routine Pap smear screening in the US, there are relatively few cervical cancer deaths — about 3,700 a year out of 10,000 cases diagnosed. But globally, HPV causes the second-highest number of cancer deaths among women. The current cost of Pap smear screening in the US is approximately $6 billion, and the cost of treating cervical cancer and its pre-cursors (therapies which, to date, consist of lesion ablation, removal of the cervix, or removal of the entire uterus) cost approximately $1.7 billion.
A number of risk factors have been identified for cervical cancer. Women who begin having sexual intercourse before age 18 and have many sexual partners are at increased risk for cervical cancer. The same holds true for sexual partners. The relevance of sexual history has to do with the chance of infection with HPV. Other risk factors include exposure before birth to the drug diethylstilbestrol (DES), smoking, and immunosuppression (e.g. HIV infection).
According to Centers for Disease and Control Prevention, more than 3700 deaths of cervical cancer in 2005 were registered in the US and cervical cancer strikes about 10,000 American women each year. HPV is the most common sexually transmitted disease, and cervical cancer kills about 300,000 women worldwide each year. WHO estimates the incidence of cervical cancer at approximately 500,000 cases per year, over 80% of which occur in developing countries, where neither Pap smears nor optimal treatment is available. The highest estimated incidence rates of cervical cancer occur in Africa, Central and South America and Asia. Cervical cancer is the leading cause of death for middle-aged women in Latin America and it is number one cause of death in women in sub-Saharan Africa and South East Asia.
The cervical cancer vaccine
A study in the US has shown that after four years a vaccine targeting HPV was still protecting women. The HPV vaccine has the potential to dramatically lower deaths from cervical cancer. Two such vaccines are ready to hit the U.S. market pending FDA approval by June 8, 2006.One is Merck’s vaccine called Gardasil, and the other is GlaxoSmithKline’s vaccine called Cervarix. Gardasil protects against the two most common high-risk types of HPV (HPV-16 and HPV-18). Gardasil also protects against two other virus types (HPV-6 and HPV-11) that cause 90% of genital wart cases. All four viruses types are sexually transmitted. Gardasil has the potential to slash worldwide deaths from cervical cancer by more than two-thirds. However, the vaccine should not replace screening since it protects against only 70% of cervical cancers caused by HPV and does not cover the many other viral strains accounting for the remaining 30% of cervical cancer cases.
Merck is seeking approval for Gardasil for females ages 9-26 because the vaccine works best when given to women before they become sexually active. Early vaccination is important because Gardasil does not necessarily protect against viruses in people already infected before they get the vaccine. By contrast, Cervarix, a rival vaccine by GSK, targets only HPV 16 and 18, and does not protect against genital warts.
The price: If approved by the FDA, women or girls would receive the vaccine (Gardasil) in three intramuscular shots over six months at a cost between $300-$500 overall. So far, Gardasil has remained potent and effective more than 4 years post-immunization. Merck, the nation’s fourth largest drug maker, considers Gardasil its most important drug candidate, as do many market analysts.
The vaccines are most effective when given before women are sexually active. What age is that? I do not know. Pre-sexual activity raises opposition from some in the U.S. who think that the vaccines may encourage sexual activity in teens by promoting the view that premarital sex is safe. Others in the U.S.A. are concerned that abstinence programs may be attacked if this vaccine is promoted. The fact that Gardasil can be administered to preteens before they become sexually active is the cause of great controversy for Christian groups. They assume that this type of vaccine will promote a view-either implicitly or explicitly-that it is appropriate for children to engage in sexual activity before marriage.
An example of such an ethical concern: Tony Perkins, president of the Family Research Council, a Christian organization that describes itself as a champion of “marriage and family as the foundation of civilization, the seedbed of virtue.” Mr. Perkin’s organization is very critical of cervical cancer vaccines. He claims that he has no intention of inoculating his 13-year-old daughter. If his daughter were to get the shots, he believes she would be more inclined to have sex outside marriage. He states that the vaccines “send the wrong message,” and that “our concern is that this vaccine will be marketed to a segment of the population that should be getting a message about abstinence.”
Despite the Family Research Council’s posturing, there is perhaps some truth in the concerns raised by Mr. Perkins. A major difference between Gardasil and other childhood vaccinations is that the latter effectively provides insurance against unforeseen environmental risks, while the former attempts to inoculate against risky personal behavior. But anticipating outcomes with any insurance provision can be a tricky business. Gardasil vaccination programs, mandated or not, could indeed create perverse incentives to engage in even riskier behavior, potentially creating a false sense of security among both the vaccinated and unvaccinated and leading to higher rates of unsafe sex and concomitant increases in other STD infections.
However, it might also be argued that the real issue for many religious conservatives Christian revolves around women’s virginity, similar to the debate over abortion. Until now, the risk of cervical cancer could be used as leverage to keep unmarried teenagers from having sex (“you will get cervical cancer!”) but now that a vaccine is available this moral high ground flattens. Some opponents of the vaccine use the example of a 13 year old pregnant girl in Florida who had a child when she was a child herself. The article explains that she was too young to be having sex or an abortion, but it fails to explain why wasn’t too young to be forced to go through childbirth. Nor does it address the main issue-that many women are needlessly dying-or placing themselves at substantial risk-from a disease that can now be effectively prevented.
This argument for rejecting the cervical cancer vaccine is equivalent to saying that seatbelts in cars are bad, because they will undoubtedly cause people to drive faster and have more wrecks. I wonder, then, how many vaccine opponents would be willing to support a law outlawing seatbelts as well?
Other ethical issues
There are still many unanswered questions and they are very important. How should the vaccine be advertised and promoted in USA and by whom? How can the vaccine be promoted elsewhere, particularly in developing world countries where the cervical cancer exerts its greatest burden?
In the U.S. it is possible that many private citizens will be able to afford the vaccines, or local public heatlth departments – or even the Federak government – could conceivably fund widespread vaccination initiatives. By contrast, the current projections of vaccine costs would be prohibitive for most developing world women. Moreover, many of the viral strains that cause cervical cancer in these countries are not covered by the current vaccines (though widespread deployment of the vaccines would still constitute a huge public health windfall). Additionally, the knowledge about HIV has spurred an increase in screening efforts in the US, on top of which increased Pap smear testing has piggy-backed. The result has been a sharp decrease in cervical cancer in the U.S., though in the developing world, as mentioned before, it still ranks second. A study by public health investigators in Mexico reported that an average of 12 women die of cervical cancer there each day. Cervical cancer is increasingly becoming a disease of poor women who have limited or no access to basic health care, much less vaccines expected to cost $300 to $500. There are a slew of other important, unanswered questions that I can only posit for this audience’s deliberation. Will the vaccine be mandated as a part of other routine immunizations? As I have mentioned the conservatives would like the vaccine not to be mandatory. Should sexually conservative parents be held morally or legally liable if they resist inoculation, or would a majority of U.S. citizens find the idea so repugnant that Gardasil would be restricted to consenting adults only? What say, if any, should
minors have in determining their sexual health, especially when their wishes run counter to their parents’ beliefs? How will the public react to the rare but inescapable instances of Gardasil-related medical complications?
Which women should vaccinated first? The younger women entering sex trade? When will they be vaccinated? Which vaccine will they get? There may be some answers to these last questions. The Center for Disease Control’s Advisory Committee on Immunization Practices will determine who should be vaccinated as soon as the FDA approves the drugs. It may recommend that preteen girls be given the vaccine, or it may recommend that teenage girls be given the vaccine, but still this is a matter open to debate and subject to the waxing and waning opinions of the American public and indeed the world at large.
My advice: stay tuned, as this controversy is not going away anytime soon.