A Viral link for Throat and Mouth Cancer

Chris - Traditionally, mouth and throat cancers have been largely associated with using tobacco products.  But in the last 20 years the incidence of these diseases has doubled, especially amongst young people.  Scientists studying the tumours have found an unexpected change - over 90% of them contain the genetic signature of the Human Papilloma Virus - HPV, which is more commonly associated with causing cervical cancer in women.

Scientists think that people having oral sex is spreading the virus to the mouth where it triggers tumours in the same way that it does in the cervix.  Maura Gillison from Ohio State University was one of the first people to spot this trend...

Maura - In 2000, we published the first compelling research that HPV is a cause of oropharynx cancers.  In 2007 we published a study in which we compared the behavior of people with cancers to the behavior of people without cancers.  And we found that oral sexual behavior was associated with risk of oropharynx cancer.  In that study we estimated that an individual with an oral HPV-16 infection had about a 15-fold increase in risk for oropharynx cancer.  The fact that most of these cancers occur in men, we're trying to increase awareness that HPV is not solely a problem for the women of the world.  The men of the world need to wake up and recognise they are also at risk for cancers caused by HPV infection.

Chris - So the same forms of HPV, because it's quite a big family of viruses, can translocate from one bit of the body, be applied to another and be equally pathogenic there?

Maura - HPV is a very unusual virus in that it doesn't travel through the bloodstream.  It's spread by direct human to human contact.  So an individual can become infected in their inner genital region from an infected partner and depending on their behaviors, that infection can also be transferred to the oral cavity.

Chris - What's the evidence that these tumours are now being caused by HPV and weren't before?

Maura - That's a very good question.  What we know from the United States is that as of about 2005, 64% of oropharynx cancers are caused by HPV infection.  We also know that in the United States over the last 20 years the incidence of these cancers has increased by approximately 200%. We do not know, through direct measurement of tumours over calendar time, that that increase is caused by HPV in the United States. However, our colleagues in Scandinavia have shown from their tumour banks, that in the 1970's, about 23% of tonsil cancers in Stockholm had HPV in them and by 2005 that had increased to 93%.  So a 70% increase over a pretty short period of time.

Chris - What if something else was making the cancers happen in the mouths of the individuals who are affected and those cells, being abnormal, are more vulnerable to getting infected with HPV?  If people are just having more oral sex which is transmitting it, maybe the effect you're seeing is just because the HPV sees more cells it can infect so you detect it?

Maura - I think the question you're asking me is, is there any evidence that HPV is there but not really the cause?  We've been able to demonstrate that the HPV is very specific to the tumour and the tumour and the virus have what's called a clonal relationship.  If you look at each tumour cell, it has the HPV in it and it's often integrated into the genome and integrated in the same place, indicating that there was one preceding event and then that clonal outgrowth turned into the tumour.  We can look at it also visually, because we've now developed very sensitive techniques for looking actually for the presence of the virus specifically in a tumour and we can create these beautiful pictures of the pathology showing HPV in the nucleus of each tumour cell and not anywhere else in the surrounding normal tissue.  So it's now accepted that the virus is indeed present in the tumours, its causal and its not just a passenger or coincident infection.

Chris - Why has the rate gone up so much in men but not in women?

Maura - That is the multi-million dollar question of the hour.  We really don't understand why that is.  We do know from women that hormonal influences do dramatically affect what happens to an HPV infection in the inner genital canal.  So given gender is really the most profound hormonal difference in humans, we really do wonder whether or not the natural history of infection may be different by men and women.  The alternate explanation is that sexual behavior differences in men and women may account for it.  In support of that are all of the studies we've done to date looking at infection.  Men have about a 3-fold increase in risk of oral infection compared to women and that's about the ratio of men:women with cancer, 3:1.

Chris - Do you think men being circumcised makes a difference?  Because it protects the female partner against cervical cancer, so if the person is shedding less HPV because they're circumcised, it might mean their partner is less exposed?

Maura - That's a great hypothesis.  It's clear from research now, both from randomised controlled trials and observational studies, that men who are circumcised have fewer infections and are less likely to transmit those infections to their sexual partners.  But all of those outcomes have been through genital infection.  We don't yet have any data showing that women who have partners who are circumcised versus those who are not are at reduced risk for acquiring an oral infection while performing oral sex on either a circumcised or uncircumcised man.

Chris - What about prevention?  You've identified there is a problem.  We can screen for these viruses to a limited degree.  What about the vaccines and things like that?  Are we in a position to do something about this?

Maura - I've been very interested in trying to find out if the currently available HPV vaccines could prevent oral HPV-16 infections.  No one in the field believes that you can get an oral cancer caused by HPV-16 without having a preceding infection.  So, if you could demonstrate that the vaccines were effective in preventing an individual from acquiring an oral HPV-16 infection, then its logical to believe then that that person would be prevented against oral cancers.  Unfortunately those studies that have been planned were cancelled.  It was a business decision on the part of the vaccine manufacturers.  So I think at this point, what we'll have to do is observe populations like in Australia where the government recognise these vaccines as potentially important as cancer prevention.  They made a very aggressive decision to vaccinate boys and girls in schools and did so with tremendous efficiency.  So now in the target age range about 80% of Australian girls and boys in the vaccine targeted age have been vaccinated.  So I think at this point we're going to have to get information on how the vaccines might reduce oral cancer through passive observation over the next 15, 20, 30 years.  Hopefully what we'll see in Australia is they've made an excellent decision for the prevention of oral cancers in boys and girls.

Chris - Let's hope so. Maura Gillison, from Ohio State University.