Human papillomavirus is a well-known and widely researched threat to womens' health. But men are at risk too, writes Maggie Koerth-Baker,—and the scientific outlook is much more uncertain.

Culturally speaking, the human papillomavirus (HPV) is a girl thing. Women get pap smears, looking for signs of HPV-related cervical cancer, as part of their regular health maintenance. When an HPV vaccine was developed, it was originally targeted at women, and women alone.

But, from a biological perspective, HPV doesn't much care about what you have going on between your legs and we're doing ourselves a disservice by ignoring that reality. In fact, as we've focused on preventing cancer of the cervix (which, for obvious reasons, really only affects women) we've overlooked a growing problem that disproportionately affects men.

Last month, actor Michael Douglas announced that his throat cancer was linked to HPV. This is not a wildly common cancer — there are about 650,000 people diagnosed with head and neck cancers worldwide every year, and oropharyngeal cancers (the kind associated with HPV) make up only a small portion of that. But the rates of oropharyngeal cancer are increasing, and so are the percentages of those cancers associated with HPV.

The people most at risk are men.

According to the Centers for Disease Control and Prevention, every year in the United States there are more than 2,370 women — and more than 9,350 men — diagnosed with HPV-related oropharyngeal cancer. The discrepancy between the sexes has always been there with oropharyngeal cancers, but we used to understand why it existed. For most of the 20th century, these cancers were primarily linked to smoking and drinking — activities that, on average, gentlemen have traditionally engaged in with more gusto than their female counterparts.

But over that last 30 years or so, that's changed. Smoking rates have declined. Research published in the Journal of Clinical Oncology in 2011 found that, between 1984 and 1989, HPV was present in 16.4% of oropharyngeal cancers. By the dawn of the 21st century, however, that number had skyrocketed. Between 2000 and 2004, HPV was present in 71.7% of all oropharyngeal cancers.

And, yet, the sex difference remained. Michael Underbrink, assistant professor of otolaryngology at The University of Texas Medical Branch said that it might be another case of men just having more exposure to the risk factors. HPV is sexually transmitted. If the average guy has more sexual partners and starts having sex an earlier age than the average woman, it would stand to reason that they might have more risk of contracting it. But Sara Pai, associate professor of otolaryngology at Johns Hopkins, said the difference might go deeper than that. There's evidence, for instance, that men's immune systems don't produce as many antibodies to fight off HPV as women's do. Far more women contract HPV than ever get cervical cancer. In fact, 95% the women who are diagnosed with HPV will successfully destroy the virus in their own bodies in short order, Underbrink said. Five percent will have more persistent infections, and only a subset of those will develop cervical cancer.

But it seems like there's something different happening with men and oropharyngeal cancer: "Both men and women are getting exposed, but men don't seem to be able to fight it off as well," Pai said.

Why there's no pap smear for men

Every two or three years, starting around age 21, many American women undergo a health ritual that would almost be mundane, if it weren't so damned strange. You take off your pants, lie on a table, and set the heels of your feet into little metal dishes that are positioned so they hold your legs up and wide apart. Then, your doctor inserts what looks like a metallic duck bill into your vagina. When she opens the duck bill, the walls of your vagina spread open, wide enough for her to stick in a tiny conical brush and a little wooden paddle. She fiddles them around a bit, then pulls all the tools out, dunks them in a vial of liquid and … you've just had a pap smear.

What about the vaccine?

So far, there's not really any data on how the HPV vaccine affects rates of HPV infection in men, or rates of oropharyngeal cancer. That's both because we don't have an easy way to test men for infection in the tonsils and because 2011 was the first year that anybody was recommending men and boys get the vaccine, to begin with. It's going to take a while for that data to come in.

In the meantime, here are four things you should know about the HPV vaccine, in general.

1) There are two HPV vaccines: Both target two of the 14 strains of HPV that have been shown to cause cancer. Those two strains were chosen because they cause 70% of cervical cancers. One of the vaccines also targets strains of HPV responsible for genital warts. This vaccine is recommended for boys as well as girls.

2) The vaccine can still be effective, even if you're already sexually active: The FDA recommendations specify giving the vaccine to people under 26, but that doesn't mean the vaccine is dangerous or definitely useless for people older than that. A vaccine against a sexually transmitted disease is going to be most effective at stopping the spread of the disease, on a population-wide level, if you're giving it to people who haven't had sex yet. Because that's who the public health officials are most interested in, that's who the vaccine has been most thoroughly tested on — and, thus, who it has been approved for. But individuals are different than populations. Just because you've had sex doesn't mean you've picked up HPV. Just because you've picked up HPV doesn't mean you have the strains the vaccine protects against. If you're over 26, it's likely your insurance won't pay for the vaccine, but it's worth asking your doctor about anyway — especially if you're a woman who has never had an abnormal pap smear.

3) If you've been diagnosed with HPV, don't panic: We don't know the statistics in men, but for at least 90% of the women diagnosed, the infection goes away.

4) The vaccine is good for at least 6-10 years. Its effectiveness probably lasts longer than that, in fact, but scientists can't say for sure yet. The vaccine hasn't been around for very long, and we're still waiting on long-term results.

The experience isn't fun. But it is an effective way to catch cancer before it develops. The brush and the paddle collect cells from your cervix that doctors study, looking for changes in the size, shape, and color of cells — changes that could be a precursor to those cells turning cancerous. The test works because we know that cervical cancer is caused by HPV, and we know how an HPV infection progresses (or, more often, doesn't progress) to cervical cancer.

That information is invaluable to helping doctors stop cancer before it starts and keep an eye on patients who have a higher risk of getting sick. In the US, our women's health care system is structured in a way that encourages regular testing — birth control prescriptions are usually doled out on a year-to-year basis, ensuring that you have to see your gyno annually if you want that no-baby pill.

There's good reason for that. Globally, cervical cancer is the third most common cancer in women. In countries where most women don't have regular access to pap smears, diagnoses of this cancer are much more common and higher percentages of women die. The less-developed regions of the world had 453,000 newly diagnosed cases of cervical cancer in 2008. Half as many women–242,000–died from the disease. Women in developed regions, in contrast, suffer only a fraction of the incidence: 76,000 new cases and 32,000 deaths.

Historically, oropharyngeal cancer hasn't had that kind of huge public health impact. In fact, it was only about a decade ago that scientists figured out the link between oropharyngeal cancer and HPV. So not only has there been less time to do the research on this, there's been less of an incentive. But, again, that's changing. That same research paper from 2011, which found rising rates of HPV in samples of oropharyngeal cancer, also found that incidence of the disease is rising as well. If current trends continue (and that's always an "if"), there could be more new cases of oropharyngeal cancer than cervical cancer diagnosed in the US by 2020.

If that happens, Sara Pai told me, it won't be easy to just start testing men for cellular changes the way we test women with pap smears. The cervix may seem like an out-of-the-way, hard-to-reach body part, but, frankly, from a medical point of view, it has nothing on the deep recesses of the back of your throat.

What's more, oropharyngeal cancers tend to start in the tonsils. That's "in", not "on". Doctors can do a pap smear because the cells they need to look at are right on the surface of the cervix.

"When HPV infects the tonsil, it's infecting fissures deep within the tonsil," Pai said.

You can't see the precancerous lesions. Most oropharyngeal cancers are detected only after cancer has started and spread to lymph nodes in the neck.

That's actually a big part of why we know so little about HPV and oropharyngeal cancer, as opposed to HPV and cervical cancer. Some of the most basic information — like the number of men who contract HPV in their tonsils compared to the number that eventually develop full-blown throat cancer — isn't available, because we haven't yet figured out an easy way to gather the data.

In many ways, the biggest problem with HPV-related oropharyngeal cancer is that it's still such a mystery. There's no test for it. And we have only enough data to know that the problem is getting bigger.

But there is, at least, a little bit of good news in all this. If you do get an HPV-related oropharyngeal cancer, it should be at least somewhat comforting to know that it's easier to treat than the tobacco-associated version from three decades ago. "It's much more responsive to chemo and radiation and there's a better cure rate over time," Michael Underbrink said. "In fact, some studies say that we don't need to treat you with as much radiation if this is what you have."

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