HPV: Sex, cancer and a virus
November 22, 2013 4:25 PM   Subscribe

"On a sunny day in 1998, Maura Gillison was walking across the campus of Johns Hopkins University in Baltimore, Maryland, thinking about a virus. The young oncologist bumped into the director of the university's cancer centre, who asked politely about her work. Gillison described her discovery of early evidence that human papillomavirus (HPV) — a ubiquitous pathogen that infects nearly every human at some point in their lives — could be causing tens of thousands of cases of throat cancer each year in the United States. The senior doctor stared down at Gillison, not saying a word. “That was the first clue that what I was doing was interesting to others and had potential significance,” recalls Gillison."
Human papillomavirus is causing a new form of head and neck cancer— leaving researchers scrambling to understand risk factors, tests and treatments.
Case–Control Study of Human Papillomavirus and Oropharyngeal Cancer
BACKGROUND: Substantial molecular evidence suggests a role for human papillomavirus (HPV) in the pathogenesis of oropharyngeal squamous-cell carcinoma, but epidemiologic data have been inconsistent.
METHODS: We performed a hospital-based, case–control study of 100 patients with newly diagnosed oropharyngeal cancer and 200 control patients without cancer to evaluate associations between HPV infection and oropharyngeal cancer. Multivariate logistic-regression models were used for case–control comparisons.
RESULTS: A high lifetime number of vaginal-sex partners (26 or more) was associated with oropharyngeal cancer (odds ratio, 3.1; 95% confidence interval [CI], 1.5 to 6.5), as was a high lifetime number of oral-sex partners (6 or more) (odds ratio, 3.4; 95% CI, 1.3 to 8.8). The degree of association increased with the number of vaginal-sex and oral-sex partners (P values for trend, 0.002 and 0.009, respectively). Oropharyngeal cancer was significantly associated with oral HPV type 16 (HPV-16) infection (odds ratio, 14.6; 95% CI, 6.3 to 36.6), oral infection with any of 37 types of HPV (odds ratio, 12.3; 95% CI, 5.4 to 26.4), and seropositivity for the HPV-16 L1 capsid protein (odds ratio, 32.2; 95% CI, 14.6 to 71.3). HPV-16 DNA was detected in 72% (95% CI, 62 to 81) of 100 paraffin-embedded tumor specimens, and 64% of patients with cancer were seropositive for the HPV-16 oncoprotein E6, E7, or both. HPV-16 L1 seropositivity was highly associated with oropharyngeal cancer among subjects with a history of heavy tobacco and alcohol use (odds ratio, 19.4; 95% CI, 3.3 to 113.9) and among those without such a history (odds ratio, 33.6; 95% CI, 13.3 to 84.8). The association was similarly increased among subjects with oral HPV-16 infection, regardless of their tobacco and alcohol use. By contrast, tobacco and alcohol use increased the association with oropharyngeal cancer primarily among subjects without exposure to HPV-16.
CONCLUSIONS: Oral HPV infection is strongly associated with oropharyngeal cancer among subjects with or without the established risk factors of tobacco and alcohol use.

Evidence for a Causal Association Between Human Papillomavirus and a Subset of Head and Neck Cancers
Background: High-risk human papillomaviruses (HPVs) are etiologic agents for anogenital tract cancers and have been detected in head and neck squamous cell carcinomas (HNSCCs). We investigated, retrospectively, an etiologic role for HPVs in a large series of patients with HNSCC.
Methods: Tumor tissues from 253 patients with newly diagnosed or recurrent HNSCC were tested for the presence of HPV genome by use of polymerase chain reaction (PCR)-based assays, Southern blot hybridization, and in situ hybridization. The viral E6 coding region was sequenced to confirm the presence of tumor-specific viral isolates. Exons 5–9 of the TP53 gene were sequenced from 166 specimens. The hazard of death from HNSCC in patients with and without HPV-positive tumors was determined by proportional hazards regression analysis.
Results: HPV was detected in 62 (25%) of 253 cases (95% confidence interval [CI] = 19%–30%). High-risk, tumorigenic type HPV16 was identified in 90% of the HPV-positive tumors. HPV16 was localized specifically by in situ hybridization within the nuclei of cancer cells in preinvasive, invasive, and lymph node disease. Southern blot hybridization patterns were consistent with viral integration. Poor tumor grade (odds ratio [OR] = 2.4; 95% CI = 1.2– 4.9) and oropharyngeal site (OR = 6.2; 95% CI = 3.1–12.1) independently increased the probability of HPV presence. As compared with HPV-negative oropharyngeal cancers, HPV-positive oropharyngeal cancers were less likely to occur among moderate to heavy drinkers (OR = 0.17; 95% CI = 0.05–0.61) and smokers (OR = 0.16; 95% CI = 0.02–1.4), had a characteristic basaloid morphology (OR = 18.7; 95% CI = 2.1–167), were less likely to have TP53 mutations (OR = 0.06; 95% CI = 0.01–0.36), and had improved disease-specific survival (hazard ratio [HR] = 0.26; 95% CI = 0.07–0.98). After adjustment for the presence of lymph node disease (HR = 2.3; 95% CI = 1.4– 3.8), heavy alcohol consumption (HR = 2.6; 95% CI = 1.4–4.7), and age greater than 60 years old (HR = 1.4; 95% CI = 0.8–2.3), all patients with HPV-positive tumors had a 59% reduction in risk of death from cancer when compared with HPV-negative HNSCC patients (HR = 0.41; 95% CI = 0.20–0.88).
Conclusions: These data extend recent molecular and epidemiologic studies and strongly suggest that HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical, and pathologic disease entity that is likely causally associated with HPV infection and that has a markedly improved prognosis.
posted by Blasdelb (37 comments total) 34 users marked this as a favorite

It is only oncogenic in the presence of chronic smoking and drinking, so there's no need to swear off the oral favors just yet
posted by Renoroc at 5:14 PM on November 22, 2013

It is just coincidental but my throat has been feeling scratchy and my "oh fuck I'm getting sick" turner into "oh fuck I have throat cancer".
posted by birdherder at 5:19 PM on November 22, 2013

Congratulations, HPV vaccine, more cancers for you to kill! Yay for vaccines.
posted by ThePinkSuperhero at 5:38 PM on November 22, 2013 [15 favorites]

Renoroc: “It is only oncogenic in the presence of chronic smoking and drinking, so there's no need to swear off the oral favors just yet”

That's the kind of thing it's a good idea to provide a citation for.
posted by koeselitz at 5:43 PM on November 22, 2013 [8 favorites]

So, uh, this "chronic" drinking...
posted by Steely-eyed Missile Man at 5:47 PM on November 22, 2013

It is only oncogenic in the presence of chronic smoking and drinking...

Actually it is completely the opposite. If you read the article linked on the front page, you'll see that this new research substantially supports the theory that there are in fact two different pathologies producing symptoms of "throat cancer" - one associated with a long life of smoking and drinking, and the other associated with presence of the HPV virus (and, frighteningly, NOT appearing only in old age after you've been abusing yourself for decades). They appear to be independent, each with its own mechanism of action and neither strongly associated with the other.

I don't mean to be pedantic but it seems important to make sure people get accurate information on this issue.

Also, I am trying to resist the urge to snark, but I wonder if it will change anyone's perspective on vaccination now that "OMG, boys can get the cancer too!!"
posted by Joey Buttafoucault at 5:47 PM on November 22, 2013 [39 favorites]

One of my good friends just finished treatment for this cancer - things seem to be OK. His wife called the cancer by his ex-girlfriends names. He also had crammed a lifetime of drinking into ten or so years but has been sober for the last 25 or so.
posted by shothotbot at 6:59 PM on November 22, 2013

It is just coincidental but my throat has been feeling scratchy and my "oh fuck I'm getting sick" turner into "oh fuck I have throat cancer".

At least you don't have tonsilloliths. Between those things and being a fellator, I'm ready to get a tonsillectomy.
posted by MikeKD at 8:40 PM on November 22, 2013 [1 favorite]

I remember reading that Tasmanian Devil facial tumor disease was probably kicked off by a PV, and was going to suggest that perhaps we could look for a human transmissible cancer out of all this, but apparently DFTD is not associated with a virus.

The formidable HeLa cell line, however, is thought to have been initiated by HPV.

And I also remember reading somewhere that Lynn Margulis believed HPV could possibly have been very important in the speciation of human beings.
posted by jamjam at 9:49 PM on November 22, 2013

Also, I am trying to resist the urge to snark, but I wonder if it will change anyone's perspective on vaccination now that "OMG, boys can get the cancer too!!"

I doubt it. The big thing on my FB feeds lately has been how Flu Vaccines are crap because the FDA approved them and the FDA also approved giving BPA laced DDT to babies instead of milk during their agent orange baths.

At some point, you just block them from your FB feed and hope their research grant gets denied.
posted by Pogo_Fuzzybutt at 10:36 PM on November 22, 2013 [1 favorite]

ThePinkSuperhero: "Congratulations, HPV vaccine, more cancers for you to kill! Yay for vaccines."

Here's hoping it leads to better and more comprehensively-effective vaccines and greater acceptance of vaccination.

The timing on this FFP was a little poignant for me -- two years ago to the day that a chunk of my cervix containing a tiny cancerous tumor was surgically removed.
posted by desuetude at 10:40 PM on November 22, 2013 [3 favorites]

Huh, I remembered that you asked about depression after a pap smear, but when I checked just now, I saw that was more than seven years ago.
posted by jamjam at 11:59 PM on November 22, 2013

My ex had to get radiation on his throat. Now he can barely eat and requires expensive medication in order to be able to raise his head up. His speech is slurred. He blames the person who introduced him to someone from whom he believes he got infected. It's sad.

I was a heavy smoker for 40 years. Fortunately I gave up heavy drinking before I turned 18. (LOL, no, really. I was in to whiskey as a teen). I've had more than my share of tonsillitis. (menthol cigarettes caused this, as evidenced by the fact it never happened again after I quit menthol!)

One side of my neck is thicker/heavier than the other. We don't know why. I have chronic inflammation of nasal passages, but it very well responds to cortisone, and is much reduced thereby. No one knows why. I haven't gotten an MRI because I'm claustrophobic. The ENT had ordered it, although she wasn't too concerned, as the "mass" in my neck isn't really obvious (and may have another explanation).

Maybe there's something in there that might spark some useful ideas for someone thinking about this stuff.
posted by Goofyy at 1:25 AM on November 23, 2013

So if as a kid I had one of those gratuitous tonsillectomies that were all the rage in the 1960's, am I in the clear for this?
posted by localroger at 6:39 AM on November 23, 2013

No you are not.
posted by sibboleth at 7:16 AM on November 23, 2013

The young oncologist bumped into the director of the university's cancer centre, who asked politely about her work.
My two favorite scientific terms-- propinquity and serendipity. This is why ideas need to bump into each other.
posted by ohshenandoah at 8:38 AM on November 23, 2013 [1 favorite]

OK, but still, FUCK YOU for blaming your cancer on someone else. That is bullshit.
posted by maryr at 11:09 AM on November 23, 2013

(Uh, generic you there, obviously. No one in thread is pulling a Michael Douglas.)
posted by maryr at 11:10 AM on November 23, 2013 [1 favorite]

Should we warn Mayor Ford?
posted by Pablo MacWilliams at 11:28 AM on November 23, 2013

No you are not.

Dangit, I thought I finally had a good reason for that to have happened when I was 5.
posted by localroger at 12:04 PM on November 23, 2013

Can someone explain why a tonsillectomy won't clear you (assuming you don't already have cancer there) as my understanding was that this was where the cancer/virus originates.
posted by Jubey at 12:22 PM on November 23, 2013

Jubey, as nearly as I've been able to discern -- bearing in mind that medical sites are maddeningly unwilling to provide a simple answer that amounts to "you won't be likely to be needing our services" -- since the tonsils are there to be crud traps, they are especially vulnerable and likely sites for all sorts of mischief, including cancer.

But even the parts of the mouth that aren't designed to be crud traps can encounter crud, though they are less likely to than tonsils. So while my tonsillectomy doesn't leave me "in the clear," it probably does reduce my risk somewhat, and perhaps quite a bit. But tonsillectomy does leave some tonsil tissue, and people do get cancers elsewhere in the mouth and throat, and tonsillectomy most likely has no effect on that risk.
posted by localroger at 2:08 PM on November 23, 2013

Tonsils aren't technically part of your esophagus. More importantly, they become pretty small as you age into the demographic that tends to have esophageal cancer, so as a function of area and probability it is unlikely. There are tonsil cancers, but I've never seen one.

On the other hand, I have seen a lot of esophageal cancers and they are generally closer to the vocal cords rather than the tongue. Your esophagus is somewhere between a foot and 18 inches long, and extends all the way down to your stomach. I seem to remember some medical bulletins describing how esophageal cancers related to decades of inflammation via acid reflex briefly passed the traditional smoking and drinking kind. Maybe the trend will reverse in light of HPV.

If there are not enough gastroenterologists in supply to give everyone colonoscopies in a timely manner to screen for colon cancer, I can't imagine what the hell we are going to do if we need to start give screening esophagogastroduodenoscopies as well.

My grasp of the basic medical sciences isn't as strong as it used to be, but I seem to recall that theoretically if you did develop a cancer in your tonsils it would either be quickly taken care of, since it's an active immune system organ similar to a lymph node, one of the main functions of the immune system is to attack tumor cells. In the alternative case, you would develop an actual, proper lymphoma. I also seem to recall that your tonsils contain the wrong type of tissue for HPV to easily infect.

Granted, as I am not a pathologist and I'm too lazy to verify all that, as a disclaimer that's just mildly informed speculation.

My own question to the thread would be, has anyone ever used a dental dam? I remember being told to advise patients to use those, but as far as I know they're a figment of public sex educator's imagination. I am glad that boys are being covered by the new regulations on using the HPV vaccine, that seemed like a particularly cringe-worthy piece of blatant American exceptionalism (misogynism?), given that ostensibly Catholic states in Latin America vaccinated both genders.
posted by hobo gitano de queretaro at 2:26 PM on November 23, 2013 [1 favorite]

Stupid question- if you're a sexually active adult, is it too late to get vaccinated?
posted by foxy_hedgehog at 2:52 PM on November 23, 2013

Not necessarily. The vaccine is ideally given prior to sexual activity, but since it protects against multiple strains (and people's bodies are often able to rid themselves of HPV strains after a period of time) getting vaccinated as an adult can still provide some protection. It can be expensive if you don't have coverage though (about $400 for all three Gardasil shots in my area).
posted by ghost dance beat at 3:00 PM on November 23, 2013

has anyone ever used a dental dam?

I seriously doubt it.
posted by localroger at 6:26 PM on November 23, 2013 [2 favorites]

Every sexually active adult should get the vaccine - even if they are an adult, and even if they have had HPV. That may not be intuitive, but there are many strains, and having one once doesn't preclude getting another later. The vaccine protects against most of the carcinogenic forms of HPV. So - no matter what, it pays to get vaccinated.

One interesting detail in this article, I thought, was the fact that Ceravix (the less-common version of the vaccine; Gardasil is much more common) apparently reduces chances of oral HPV infection by 93%. That's very effective - almost as effective as condom use. I'm not sure if this has been tested for Gardasil, but I'd guess the rates are similar. So - if you're relatively sure there aren't many other risks (particularly if you have a consistent monogamous partner) just making sure the two of you are vaccinated is probably a good alternative to physical barriers during oral sex.
posted by koeselitz at 6:26 PM on November 23, 2013

Here is what the CDC says:
Cervical cancer: About 10,300 women in the U.S. get cervical cancer each year.

Other cancers that can be caused by HPV, including some vaginal, vulvar, penile, anal, and oropharyngeal cancers: Each year in the U.S., HPV is thought to cause an estimated

2,100 vulvar cancers,
500 vaginal cancers,
600 penile cancers,
2,800 anal cancers in women,
1,500 anal cancers in men,
1,700 oropharyngeal cancers in women,* and
6,700 oropharyngeal cancers in men.*

*Note: Other factors, notably tobacco and alcohol use, may also play a role with HPV to cause these cancers.

About 21,000 of these cancers are potentially preventable by HPV vaccines.
To put this in perspective, there are about 1.6 million new cancers in the US each year. Progress against cancer seems to be slow but steady -- five-year death rates are falling at about 1.5% per year. This is roughly in the neighborhood of the number of cancers per year in the US that are preventable thanks to the HPV vaccine.
posted by compartment at 11:17 PM on November 23, 2013

If I go to CVS or whatever and ask for the vaccine, will they give it to me (>26 year old male)?
posted by professor plum with a rope at 2:28 AM on November 24, 2013

You need a doctor's prescription for it, and for Gardasil it's 3 shots over a period of 6 months (not sure about Ceravix). If your family doctor won't give it to you, try your local Planned Parenthood. Mine will give it to those who ask, even if you're outside of the suggested age range.
posted by ghost dance beat at 6:49 AM on November 24, 2013 [2 favorites]

My experience as an adult male getting it was that it was pretty easy; as ghost dance beat says, it takes 3 shots over 6 months. I got Gardasil at the age of 31. I did this at Planned Parenthood. You should check with your health insurance; unfortunately it often isn't covered, but sometimes it is. It wasn't for me, so I ended up paying about $200 total for the course of vaccination. Family doctors might be cheaper, and (as I said) health insurance may cover some of it. It was worth it for me just for the peace of mind, though.
posted by koeselitz at 10:51 AM on November 24, 2013 [1 favorite]

I thought the vaccine was only useful if you've never been sexually active? If you are, the chances of exposure are already quite high.

Edit: I saw the question was already asked. Oops.
posted by FJT at 12:00 PM on November 24, 2013

Thanks, koeselitz; I was wondering scrolling down if insurers would cover it for people over the age of 26.
posted by ThePinkSuperhero at 6:24 PM on November 24, 2013 [1 favorite]

It actually hasn't been studied as much among populations over 26, so the FDA hasn't allowed Merck to market Gardasil to women over 26 since they can't back it with the same almost-perfect claims of HPV prevention for older women. (They never even thought about marketing it to men of any age.) It's ironic, because I think generally pharmaceutical companies should probably dial back on their marketing. However, unless you believe that there is something magical that happens in the human body at the age of 26 (which seems unlikely to me) HPV vaccinations still seem like a great idea. From what I've heard, there are a lot of cutting-edge doctors in the field who are pushing to see it more widely done.

Personally, my take on the situation is this: Merck and GlaxoSmithKlein (the makers of the HPV vaccines) know very well that their biggest market is women ages 18-40. These are the sexually-active people who care enough to pay for birth control and body health medications. It was a blow to them that they couldn't market to the 27-40 bracket; but they're not going to push it too hard, because (a) the 18-26 people are probably a bigger market anyway and (b) there's a lot of conservative resistance to these kinds of drugs. They hate to make conservatives nervous, and messages like "you should get your daughters innoculated against SEX DISEASES" make conservatives nervous. And men – well, men don't care at all (think the marketing people) and trying to sell contraceptive/sex drugs to them is pointless.

At the end of the linked article above, Dr Maura Gillison (the subject of the piece) says: “In terms of cancer, there aren't many populations where we've identified the necessary cause and have a potential solution on the shelf.” She's damned right: the fact that there's a vaccine for the cause of this type of cancer is astounding, and ought to be cause for quick action and celebration, in that order. How many cancers can we actually vaccinate against and thereby potentially eliminate entirely? The trouble that we as a society are slow on the uptake as far as really useful vaccines are concerned. This is a case where it's likely to be even worse, because it involves sexually transmitted disease, and sexually transmitted diseases are complicated and make a lot of us nervous.

But this is a chance for us to be ahead of the curve and to act in the interest of ourselves and our future. Within the next few years, there will almost certainly be a big push to see HPV vaccines adopted more regularly throughout society. I think it's a really spectacular thing to be one of the first to say: "the data is clear, and I'm going to stand with science and with the future and get vaccinated now."

We'll probably hear more and more about this in the coming years, and there will probably be some battles about it. A lot of people hate the idea of their daughters (and sons) getting vaccinated because they hate to imagine their daughters (and sons) having sex. This has the potential to be even more divisive than the petty fringe squabble over the MMR vaccine. It's going to be essential that we convince the American public that people have sex, and that, whether we think that's a sin or whatever, we want to build a world where they don't have to face cervical, anal, or throat cancer as punishment for having sex.

That's why I think HPV vaccination is pretty darned important. And I think we all should get used to making these arguments; because, in the next few years, we'll probably find ourselves facing our neighbors, our families, and our friends trying to explain why it's a good idea to vaccinate young girls and boys against a "sex disease." They'll hate to hear it initially; that's why we have to be ready to explain this to them.
posted by koeselitz at 9:23 PM on November 24, 2013 [2 favorites]

jamjam: "Huh, I remembered that you asked about depression after a pap smear, but when I checked just now, I saw that was more than seven years ago."

Yep, apparently my cervix doesn't like getting scraped and tells me so with a little hormonal hissyfit. It's...a phenomenon with which I am now very, very, very familiar, since I now get paps and often colposcopies several times a year.

I never had an abnormal pap until the one that led to the cancer diagnosis. On paper, my risk factors were very, very low. And yet. Get your little girls vaccinated, parents.
posted by desuetude at 7:40 AM on November 25, 2013 [2 favorites]

Renoroc: "It is only oncogenic in the presence of chronic smoking and drinking, so there's no need to swear off the oral favors just yet"

Joey Buttafoucault: "Actually it is completely the opposite.... I don't mean to be pedantic but it seems important to make sure people get accurate information on this issue."

You're not being pedantic; Renoroc said something 100% incorrect about a life-threatening issue. From TFA, emphasis added:

"Oral HPV infection is strongly associated with oropharyngeal cancer among subjects with or without the established risk factors of tobacco and alcohol use.
posted by IAmBroom at 1:38 PM on November 25, 2013 [1 favorite]

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