It's nice to see you. It's great to see you. So let's have a look-- OK. --at you. And I don't have a [INAUDIBLE] anymore. I'm a practicing head and neck medical oncologist. And so I frequently see patients when they're first diagnosed with cancer. I had a sore throat, and I had an earache, which I attributed to allergies. And I totally ignored it. And it wasn't until my tongue started hurting that I went actually to WebMD and they said, oh, you have oral cancer. For a long time, head and neck cancer was largely attributed to lifetime use of tobacco and alcohol. But in the mid '80s and then definitely by the mid '90s, the proportion of patients who did not have a smoking and alcohol history started to go up. You didn't have any of those classic risk factors, did you? I smoked one day in sixth grade. But besides that, no. They present often feeling great. They don't have a history of alcohol and tobacco. So it became clear that this was actually a very different disease, one in which a virus is causing the cancer. Cancer is basically disrupted control of growth of a cell that then can spread and act in ways that it doesn't normally act. It was a shock to me. I met with Dr. [? Tufano. ?] And after meeting with me for five minutes, he said you have a 3 and 1/2 centimeter tumor in your tongue. It's. Life-threatening and that's when he said, I think it's HPV. We're going to run a biopsy [INAUDIBLE].. HPV is human papillomavirus. About 20,000 people in the United States are diagnosed each year with a cancer caused by HPV. The majority of those are cervical cancers. The other 9,000 to 10,000 are non-cervical cancers. HPV infects the basal cell layer of skin. And then basically takes over the machinery of the cell in order to make itself. From the virus's perspective, the virus is just trying to survive. So it's thought to be an accident of the fact that the virus has these genes that take over the cell's machinery to reproduce itself, but as a consequence of that, causes damage to the cell's own ability to control its own growth and then subsequently leads to cancer. Recovering from the treatment was harder than recovering from the disease. And you don't even realize how much it's taking out of you because having chemo and radiation every day for 35 days-- Over the last 15 years, the therapy for head and neck cancer has become increasingly intense. Different institutions use different chemotherapy protocols, different radiation protocols. They might get surgery alone followed by radiation, chemotherapy with radiation. But once you know an infection contributes to the development of a cancer, you can try to take advantage of that. To understand how papillomaviruses cause cancer, I believe that you have to study how these viruses have evolved. Do you think that's a positive there? No, [INAUDIBLE]. The papillomaviruses are the whole family of viruses. So if you look at groups of viruses which have common ancestors and that some are very cancerous and some are not, that will tell us more about what properties a virus has evolved that then subsequently and unfortunately also lead to cancer. So then we're trying to correlate the evolution of the different HPV types with their ability to degrade P53. Yes. So the virus has to replicate it's DNA. Now, the cell has a protective way of stopping that through the P53 protein, which is the master regulator in the cell. So the viruses degrade the P53 protein to allow the virus to replicate in the tissue. Unfortunately, disrupting P53 also causes cell growth and division. So HPV 16, which is the most cancer causing of the HPV types, completely degrades P53. But look here how HPV 53, which has a common ancestor to all the oncogenic types also degrades P53. Lo and behold, what we find is that within papillomavirus family, there are many that degrade P53, but do not cause cancer. So we can't assume that P53 degradation is the full story. It could be that the ability to degrade P53 is necessary, but not sufficient. So you need it, but then there's something else or some other property [INAUDIBLE],, which is more important. As we learn more about the actual mechanisms, we could target the papillomavirus products in the cancer tissue. And I think that that would have therapeutic potential. Now, I can tell you do have some dry mouth from the therapy, but your voice has come back to normal. It's almost normal. Yeah, nothing that affects the quality of my life. Are there things as a consequence of the therapy [INAUDIBLE]? It's clear that HPV in the tumor is going to be a major factor in determining how people get treated. There's a lot more research that remains to be done to target treatment specifically for the HPV-infected tumor cell. But as a cancer specialist, I'd much rather prevent the cancer in the first place than treat it. For HPV-caused cancers, we've identified, really, the Achilles heel. If you don't get HPV infection, you don't get the cancer. We can prevent these cancers with a vaccination. Now, you're going to feel a little pinch. The vaccine has been shown to be extraordinarily effective against cervical infections that lead to cancer and precancers. And we're very optimistic in the oral cancer field that the vaccine will have an important impact over time on rates of HPV infection. The availability of an effective papillomavirus vaccine, which can prevent the major types of papillomavirus that cause about 70% of the cervical cancer is a huge breakthrough. And it really represents the work of the entire field. People studying natural history, the molecular biologist, the physician. It's really a cumulative accomplishment of our field. [MUSIC PLAYING]
