1. Sledge, George W. JR., MD

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Lately I've been thinking about nuns and moral hazard and the nexus of epidemiology, prevention, economics, and politics. It's a long story, and complicated, and value-laden in the way medical science so often seems to be these days. So follow closely: lots of connections, and not all of them obvious.

GEORGE W. SLEDGE JR.... - Click to enlarge in new windowGEORGE W. SLEDGE JR., MD, Immediate Past President of the American Society of Clinical Oncology, is Ballve-Lantero Professor of Oncology and Professor of Medicine and Pathology at Indiana University Simon Cancer Center. Write to him about this essay or other topics at, or add comments directly on his OT blog, at

Let's start with the nuns. Nuns are epidemiologically ineresting in that they are a well-defined population with special lifestyles (chastity, poverty, and obedience, but we'll focus on chastity) with medical implications. This has made them a subject of interest for epidemiologists, who love defined populations that they can compare with the general population.


Our story begins in 1713, when the Italian physician Bernardino Ramazzini wrote De Morbis Artificum Diatriba, or "Diseases of Workers," the first major work on occupational medicine. Ramazzini noted that nuns developed breast cancer at a much higher rate than married women, which he attributed to the deleterious effect of sexual abstinence on breast tissue. You can imagine young Bernardino's pick-up lines: "You don't want to get breast cancer, do you? Trust me, I'm a doctor on the University of Padua faculty."


Later epidemiologists noted that the increased risk of breast cancer was counterbalanced by a decreased risk of cervical cancer. Prostitutes, in contrast, were thought to experience an increased risk of cervical cancer.


Apparently too much sex was bad for you, as was too little: a fine example of the sort of controversy epidemiologists always seems to attract. In recent decades we've learned that both of these old observations were attached to underlying biologic truths. Nulliparity and lack of breastfeeding increase breast cancer risk, and women who don't have sex don't contract the human papillomavirus (HPV) infections causing cervical cancer.


But if HPV (or certain HPV subtypes) lead to cervical cancer, can we prevent cervical cancer by preventing HPV infections? The answer, we now know, is yes. The science that got us there once again involved nuns.


When Dr. William Bonnez of the University of Rochester, one of the early leaders in HPV vaccine development, wished to develop a blood test for HPV, he called upon the virginal Sisters of St. Joseph in Rochester. Their sera served as the negative control samples for Bonnez's initial HPV ELISAs.


The last decade saw the testing and FDA approval of two cervical cancer vaccines. These vaccines clearly reduce the risk of both HPV infection and subsequent cervical cancer: a triumph for modern biology and preventative medicine. Except that nothing in prevention is ever easy. Not everyone was happy with the vaccines.


Opposition came from a number of sources. Some had moral objections: wouldn't vaccination of young girls lead to an increase in sexual promiscuity? Like most physicians I find this thought process an odd one. I don't want women to die of cervical cancer, and preventing those deaths seems worthy in and of itself. And a single HPV-infected male partner is all it takes to get infected.


On a personal note, my grandmother died of cervical cancer in the pre-Pap smear era. It was a slow, painful, miserable death that permanently traumatized my mother, a teenager at the time. I never got to meet my grandmother. She died before I was born, and I know essentially nothing about her other than her illness, and the sad hole it left in the center of a family.


I have doubts that vaccinating young women will rob them of their virtue: young men happily do that regardless of vaccination status. But I cannot rule out the possibility that technology will once again alter sexual morality. Oral contraceptives changed sexual morality, after all, as did penicillin. I'm sure an effective AIDS vaccine would do the same. Which brings us to the concept of moral hazard.


Economists, a generally amoral group, use the term "moral hazard" to describe the situation in which a party insulated from the consequences of an activity behaves in a more risky fashion. If a "too big to fail" bank knows it will be bailed out by taxpayers when it makes risky bets, it will be more likely to make those bets. Unsurprisingly, moral hazard was one of the favorite economic terms of 2008.


Economists worry about the moral hazard issue in medical care: if insurance pays for everything medical, won't patients just use a lot more medical care, jacking up overall health care costs? Well, yes and no. Early health care expenditures for preventable causes of death keep people out of expensive emergency rooms and intensive care units. The economics of moral hazard in healthcare are complex, with trade-offs galore.


But the moralists are concerned about the moral (or immoral) aspects of moral hazard. I'm a pragmatist, like most doctors: insisting that I can't prevent people from dying because they either did or might do something someone else considers wrong means that I cannot treat a lot of diabetics, heart attack victims, lung cancer patients, STD patients in general, people who need knee replacements, motorcyclists' head trauma, and who knows what else. Let's not get started down that road: it always leads to you, my friend.


Another source of opposition to HPV vaccinations comes from those who oppose mandatory vaccinations. Governor Rick Perry was savaged by his fellow Republican presidential aspirants for an executive order mandating HPV vaccinations for young Texas girls. Republicans as a party now oppose healthcare mandates of all sorts, but one wing of the party apparently views mandatory vaccinations to be a violation of civil liberties.


Doctors, who learn about the virtues of herd immunity in medical school, and who consider fatal infectious diseases to be particularly disrespectful of human rights, tend to support mandatory vaccinations. Others in the general public disagree.


There is also the nutcase party, which has seen a huge resurgence in the past decade. The nutcase party considers vaccines in general to be evil. The nutters came out in force over the (phony) connection between vaccination and autism, a debate that probably resulted in the deaths of innocent children. More recently we have a Republican candidate from Minnesota claiming that HPV vaccines cause mental retardation. I will pass on the obvious rejoinders.


Governor Perry's case is complicated by another form of moral hazard: the chief lobbyist for Merck, one of the HPV vaccine makers, is Perry's former chief of staff, and Perry has received a campaign contribution from the company. If campaign contributions and revolving-door cronyism save lives, is that a moral or an immoral thing? Perry, meanwhile, said that he was insulted to be thought capable of being bought with a $5000 campaign contribution. He is undoubtedly being sincere: it takes a much larger campaign contribution to buy a Texas governor.


There are real issues surrounding the HPV vaccines, mostly circling around health economics. The vaccines are far more expensive than we would like for a public health intervention. The number of preventable cervical cancer deaths in the United States with universal vaccination is small in the grand scheme of things, and we already have appropriate public health interventions (the Pap smear and HPV testing) that allow for early detection and subsequent prevention of cervical cancer mortality. The benefits accrued through vaccination may occur decades in the future, while the costs are immediate. So the cost: benefit analysis is not entirely straightforward.


Outside the United States the story becomes simpler. In most low and middle income countries cervical cancer is a leading, rather than a minor, cause of cancer death. Population-based Pap smears are simply unavailable (insufficient gynecologists, insufficient pathologists, insufficient money), and vaccination would significantly alter the grim toll of this disease. If it was affordable: another moral dilemma tied up in the knots of health economics.


The Gates Foundation, through the GAVI Alliance, has come to the rescue, to its very great credit, and vaccine makers are offering reduced prices for the developing world. The nutters and conspiracy theorists (many on the left of the political spectrum: the right has no monopoly on nonsense when it comes to vaccines) are already attacking Bill Gates for doing the right thing. If an evil Western capitalist, working with evil Western drug companies, wants to vaccinate poor people in the developing world, then vaccines must be evil and designed to poison the poor. Just Google "Gates Foundation" and "HPV" to see a catalog of venomous paranoid fantasies.


There's more to the HPV story, of course. When I was in training, head and neck cancer was a matter of too many cigarettes and too much booze (medical hazards and moral hazards combined). HPV-induced head and neck cancers, related to oral sex, have exploded in recent years.


These cancers are interesting to scientists in that they have a lower mutational load, fewer p53 mutations, and better overall prognosis than cigarette-induced head and neck tumors. Interesting scientifically, but still tragic if you have one. Current predictions are that HPV-induced oropharyngeal cancers will outnumber cervical cancers in a little over a decade.


Unless, that is, we prevent the emerging epidemic with the HPV vaccine. We lack trial data demonstrating such an effect, but emerging data clearly demonstrate reduced rates of HPV-induced condyloma, anal intraepithelial neoplasia, and anal cancers in at-risk male populations. So it is reasonable to expect a similar effect on the head and neck cancers. The CDC's modelers predict that routine HPV vaccination of boys aged 11-12 would prevent around 2400 head and neck cancers per million vaccinated over a lifetime.


The Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) voted in October to recommend the routine use of the human papillomavirus quadrivalent vaccine (HPV4) in boys aged 11 to 12 years. Mothers, if you want to protect your daughters, ask whether the boys they are dating have been vaccinated. And get your daughters vaccinated too.


Let's circle back to the nuns. I mentioned earlier that epidemiologists love nuns. Well, love them as experimental subjects, love them in the abstract, figurative sense: I don't want to leave any wrong impressions. Epidemiologists, like nuns, are highly moral people. They have conducted numerous nun-based studies in recent years, including a major Alzheimer's project run out of the Mayo Clinic.


One study that caught my attention had nothing to do with cancer. Deborah Danner and colleagues, writing a decade ago in the Journal of Personality and Social Psychology (80:804-13, 2001), looked at handwritten autobiographies of Catholic nuns written in their early 20's. With six decades of follow-up, the nuns with the most positive emotional content in their autobiographies were the least likely to die at an early age. Nuns to world: be happy! You'll live longer. There's nonsense and there's nun-sense: go with the nuns.


More from George Sledge on His OT Blog!


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