Does bestiality increase your risk of penile cancer?

Aah, the things one learns when awake at 3AM on a Saturday night. Via a few different Tweeps, I ran across this article from Men’s Health magazine, titled “Urgent Warning: Sex with Animals Causes Cancer.”

I probably should have just stopped there.

But no, I read the magazine article, which states:

Brazilian researchers polled nearly 500 men from a dozen cities, and found that–we’re not joking around here–roughly 35 percent of the men had “made it” with an animal. That’s a problem, because screwing a horse, donkey, pig, or any other animal was found to up your likelihood of developing cancers of the penis by 42 percent.

Of course, this meant that now, I had to go dig up the actual journal manuscript. Though nothing is cited by Men’s Health, a quick PubMed search using the terms “sex with animals” and “Brazil” turned up Sex with Animals (SWA): Behavioral Characteristics and Possible Association with Penile Cancer. A Multicenter Study, published last month in The Journal of Sexual Medicine.

Though the MH write-up makes the research sound ridiculous, it’s not a bad paper overall. Starting out with the observation that penile cancer is common in impoverished regions in the world but relatively rare in developed areas, the authors wanted to examine one possible difference in this urban/rural divide: bestiality. So they enrolled 492 individuals who had spent their childhood in rural areas: 118 cases who had penile cancers and 374 controls who were seen at the same clinics for other issues, including check-ups and “cancer prevention” (though it’s not really defined what’s included in that catch-all). All participants were asked a variety of questions about their sexual history, including sex with animals and humans (frequency, number of partners, the usual drill), circumcision status, as well as other factors that might influence cancer outcomes, such as smoking status and history of sexually transmitted diseases and other health conditions.

The authors did find in the univariate analysis (basically, looking at one factor at a time) that there were several statistically significant differences between the cancer group and the control group. These included smoking, a history of sex with prostitutes, the presence of penile premalignant lesions (not surprising) and phimosis (NSFW), a condition where “the foreskin cannot be fully retracted over the glans penis.” As the title suggests, they also found that having sex with animals was significantly higher in the case than the control group (44.0 vs 31.6 percent, p<.008). When they combined risk factors into their multivariate analysis, a few factors still remained in the model. Phimosis was the big one, with an odds ratio of 10.41; SWA was down the list at 2.07 (95% CI: 1.21-3.52, p=0.007). Penile premalignant lesions and smoking also remained, with odds ratios in the middle of the other two. Finally, just because I know many of you out there are curious, they also break down those who have SWA by types of animals they, um, frequent:

The animal types most often cited were mares (N = 80), followed by donkeys (N = 73), mules (N = 57), goats (N = 54), chickens (N = 27), calves (N = 18), cows (N = 13), dogs (N = 10), sheep (N = 10), pigs (N = 6), and other species (N = 3).

Yes, chickens for 27 of them. I don’t even want to know, but I’m sure if I did, I could find out somewhere on the Internets. Please, don’t educate me on that one. They also note that almost a third of the men reported “SWA with a group of men.” I’m leaving that one alone as well (especially as that one wasn’t any different between cases and controls, so it didn’t seem to be an important variable for penile cancer development).

So how do they explain these findings? Their discussion is a bit odd, in my opinion, and narrows in on the SWA finding to the exclusion of their other significant risk factors. Of course, coming from my background, my first thought regarding SWA and cancer jumps to infectious agents. They acknowledge in the introduction that the human papillomavirus (HPV) is associated with about half of penile cancers. Other species of animals can also be infected with papillomaviruses, such as the rabbit of jackalope mythology. A previous study identified five potentially novel papillomaviruses in Australia, just by doing skin swabbing. As such, it’s certainly safe to say that we know very little about the diversity of these viruses that exist in other animal species, much less their cancer-causing potential. It would be fascinating to look at tumor samples from the men in this group who were known to have sex with animals, and see if any novel viruses (papillomas or otherwise) could be identified.

However, they don’t limit their suggestion to only zoonotic infections. That’s when it gets a bit weird to me, as they say things like:

Speculation exists regarding cancer status as an infectious disease in humans [24,25], as studies have suggested that tumor cells can be transmitted from one mammal host to another within the same species [26,27]. PC is frequent in equines [28], but transmission of malignancies between animals and humans has not been reported.Virology does not consider possible viral movement from animals to humans except in cases of zoonosis, such as rabies or pandemic forms of bird or swine flu. However, the hypothesis that the HIV epidemic resulted from simian-human virus transmission has not been fully explored.

Um, huh? First, the citation they use for the HIV claim is from 1999–indeed, at that point there was still a lot that was unknown about cross-species HIV transmission, but that was 12 years ago! The field has moved on since then. I’m baffled as to what they mean by their first sentence–as far as I know, “Virology” doesn’t consider anything–“Virologists” do, and why would this not be a zoonosis? Though I think direct transmission of cancer cells (like in the case of the Tasmanian devil transmissible cancer) would be unlikely, transmission of microbes which could lead to cancer development is certainly plausible and well within the realm of virology/bacteriology/etc. In my opinion, it’s infinitely more likely than the idea they also suggest of more directly carcinogenic animal secretions.

There were also a number of limitations in the paper. Though they grouped frequency of sex with prostitutes into a “more/less than ten times” dichotomous variable, I don’t see any similar “dose” analysis for the frequency of SWA in their models, even though they did ask the men about this. They make one statement that “long-term SWA (>3 years) was reported by 64% of the PC patients and 46.6% of the controls (P = 0.044).” This difference was statistically significant at the usual cutoff (p< .05), but it doesn't appear that they studied this further--why not? If you have a typical dose-response relationship (the more times the men had sex with animals, the more likely they were to develop cancer in the future), that would strengthen their case for a connection between the two. They also didn't ask about sexual orientation or the nature of the self-reported past STDs. Are any of these participants HIV positive, for example? Anyway, with these limitations in mind, it does appear that Men's Health got it mostly right: don't have sex with animals if you value your penis. But it's unfortunate that they just go for the sensationalism and ignore the more important variables from a public health standpoint, like "don't smoke" and "if you have abnormal penile conditions, you may want to get those checked out, k?" References

Zequi SD, Guimarães GC, da Fonseca FP, Ferreira U, de Matheus WE, Reis LO, Aita GA, Glina S, Fanni VS, Perez MD, Guidoni LR, Ortiz V, Nogueira L, de Almeida Rocha LC, Cuck G, da Costa WH, Moniz RR, Dantas Jr JH, Soares FA, & Lopes A (2011). Sex with Animals (SWA): Behavioral Characteristics and Possible Association with Penile Cancer. A Multicenter Study. The journal of sexual medicine PMID: 22023719

Antonsson and McMillan, 2006. Papillomavirus in healthy skin of Australian animals.

Hemolytic uremic syndrome (HUS) in history–part 4: the bigger picture

As I’ve laid out this week (part 1, part 2, part 3), the realization that a fairly simple, toxin-carrying bacterium could cause a “complex” and mysterious disease like hemolytic uremic syndrome came only with 30 years’ of scientific investigation and many false starts and misleading results. Like many of these investigations, the true cause was found due to a combination of hard work, novel ways of thinking, and simple serendipity–being able to connect the dots in a framework where the dots didn’t necessarily line up as expected, and removing extraneous dots as necessary. It’s not an easy task, particularly when we’ve had mostly culture-based methods to rely on since the dawn of microbiology.

If you read start digging around in the evolutionary medicine literature, you’ll see that one oft-repeated tenet is that many more “chronic” and “lifestyle” diseases are actually caused by microbes than we currently realize. (I’ll note that there is active disagreement here in the field–one reason noted is that many of these diseases would decrease one’s fitness and thus they are unlikely to be genetic, but many of them also have onset later in life than the prime reproductive years, so–still controversial). But whether you agree on the evolutionary reasoning or not, I think it’s safe to say that those who make this claim (like the Neese & Williams book I linked) are probably right on the overall assertion that more and more of these “lifestyle/genetics” diseases are going to be actually microbial in cause than we currently realize.

Why do I agree with this claim? History is a great indicator. Many infectious diseases were thought to be due to complex interactions of genetics (or “breeding,” “lineage,” etc.) with “lifestyle.” Think of syphilis and tuberculosis in the Victorian era. Syphilis (and many other diseases which we know now to be sexually-transmitted infections) was considered a disease which affected mainly the lower social classes (“bad breeding”), and was thought to be rooted in both family history as well as an over-indulgence in sex or masturbation. Tuberculosis, because it affected those throughout the income spectrum, was still blamed on “poor constitution” in the lower classes, but was a disease of the “sensitive” and “artistic” in the upper classes. It was also thought to be due to influences of climate in combination with genetics. Or, look to more recent examples of Helicobacter pylori and gastric ulcers, which were also ascribed to dietary habits and stress for a good 30 years before their infectious nature was eventually proven. And from that same era, HIV/AIDS–which even today, some are still all too ready to write off as merely a behavioral disease, rather than an infectious one.

So, we still view many of these diseases of unknown etiology as multi-factorial, “complex” diseases. And undoubtedly, genetic predisposition does play a role in almost every infectious disease, so I’m not writing off any kind of host/pathogen interplay in the development of some of these more rare sequelae, such as HUS as a consequence of a STEC infection. But looking back over history, it’s amazing how many diseases which we view now as having a documented infectious cause were studied for years by researchers thinking that the disease was the result of exposure to a toxin, or diet, or behavior, or a combination of all three.

I’ve mentioned the example of multiple sclerosis in previous posts. Multiple sclerosis is an autoimmune disease; the body produces antibodies that attack and eventually destroy parts of the myelin sheath covering our nerves. The cause of MS, like HUS 40 years ago, is unknown, though it’s thought to be a combination of genetics and environmental influences. Going through the literature, it seems like almost everything has been implicated as playing a causal role at one point or another: pesticides, environmental mercury, hormones, various other “toxins,” and a whole host of microbes, including Chlamydia pneumoniae, measles, mumps, Epstein-Barr virus, varicella zoster (chickenpox), herpes simplex viruses, other herpes families viruses (HHV-6 and HHV-8), even canine distemper virus. They’ve done this looking at both microbe culture (from blood, brain tissue, CNS, etc.) as well as using serology and DNA/RNA amplification in various body sites. None have shown any strong, repeatable links to the development of MS–much like the spurious associations that were seen with adenovirus and HUS.

Although no microbial agent has been convincingly implicated to date, there are tantalizing hints that MS is caused by an infectious agent. There have been “outbreaks” of MS; the most famous occurred in the Faroe Islands in the 1940s. Studies of migrants show that the risks of developing MS seem to be tied to exposures in childhood, suggesting a possible exposure to an infectious agent as a kid. And one of the most common mouse models used to study MS has the disease induced by infection with a virus called Theiler’s murine encephalitis virus (TMEV). If it can happen in mice, why not humans?

It might seem implausible that infection with some microbe could lead to the eventual neurological outcomes of MS, but again, examples abound of weird connections between microbes and health outcomes. For STEC, it might not be intuitively obvious at first glance how a fecal organism could be a cause of kidney failure. The respiratory bacterium Streptococcus pyogenes usually causes throat infections (“strep throat”), but if left untreated, it can also cause kidney damage (glomerulonephritis) or even heart failure due to rheumatic heart disease. A microbial cause of MS could lie in a virus, bacterium, parasite, or fungus–maybe one that we haven’t even discovered yet, but that perhaps will pop up as we learn more and more about our metagenome. Perhaps 30 years down the road, the way we view many of these “complex” diseases will look as short-sighted as it does looking back at old HUS papers from today’s vantage point.