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> Welcome to Cancer newsline, a podcast series from the University of Texas M.D. Anderson Cancer Center. Cancer newsline helps you stay current with the news on cancer research, diagnosis, treatment, and prevention, providing the latest information on reducing your family's cancer risk. I'm your host, Lisa Garvin, and today we'll be talking about one of six new cancer moon shots that have been identified by M.D. Anderson. This moonshot focuses on the human papilloma virus and its relation to several types of cancer. I have with me two guests to talk about this, Dr. Kathy Eng [phonetic] who is a professor of gastrointestinal medical oncology and Dr. Eric Sturgis, a professor of head and neck surgery but the principal investigator on the HPV moon shot. Dr. Sturgis let's talk about HPV-related cancers. I think we all know that cervical is one but there are several cancers that have an HPV basis.
> Yes, so the virus and its link to cancer was really established with cervical cancer and the understanding of how cervical cancer develops and that was really the model for how this virus causes cancer and now we understand that several other cancers are related to HPV and are chiefly caused by HPV those being anal cancer, penile cancer in men. Other cancers in women include vulvar cancer and vaginal cancer in women and then in both men and women oropharyngeal cancer which is cancers of the throat principally the tonsils and the base of the tongue, the very back of the tongue, the part of the tongue you can't see. It's sometimes referred to the part of the tongue that's in the throat or the lingual tonsils it's sometimes referred to.
> And of course we've made big strides with HPV with the introduction of Gardasil, a vaccine that has a high success rate if given at the right time and in the right circumstances.
> That's correct. Gardasil and the other HPV vaccine Cervarix, both of these protect against the types of HPV virus that can cause cancer, particularly type 16 and 18 and one thing to keep in mind is these cancers develop in middle age so for oropharynx cancer it's in the mid-50s that most people develop this. Kathy can talk a little bit about anal cancer and when that usually shows up, but the importance is preventing infection or chronic infection or persistent infection which seems to be so critical to preventing later development of the pre-cancers and then ultimately the cancer so it's critical that we're targeting this at adolescence and getting those vaccination rates up is what we're going to see downstream, years down the road, drops in the numbers of these cancers.
> So Dr. Eng the goal is pretty lofty for this moon shot as far as the vaccination rate?
> So in regards to the vaccination rate I mean our goals I think if I recall is to have at least 80% of age-appropriate individuals get vaccinated appropriately. The reality is is at least because I just gave a presentation on this recently, on the CDC website in the U.S. and obviously it varies state-by-state but in general four out of every ten girls are not vaccinated appropriately in six out of every ten boys are not vaccinated appropriately and of the girls that are vaccinated at least the last time I checked once again it was about 30 or so percent -- , I'm sorry only 30 plus percent received all three vaccinations and for boys about 14% have received all three vaccinations if they've been vaccinated. So we've got a hefty goal to achieve.
> And obviously public awareness, there were a couple of stumbling blocks to public awareness especially here in Texas. We've seen that people seem to connote that with earlier sexual activity. Have you been able to get over that hump?
> We're trying very, very hard and honestly our president of this institution, Rhonda [inaudible], has been a huge advocate for us as a group, for the hospital as well, and working with members of Congress to really get the information across at least for the state of Texas. I think that's really important, and also Lois [inaudible], one of our colleagues, she's working with the GOG if I'm correct, for instance I'm working with the American Society of Clinical Oncology as well to create a consensus statement to try to get that information across nationally and to encourage people to make sure they understand we're not just focusing -- , I mean the whole point of this is really to prevent cancer. We're not promoting sexual promiscuity. This is to prevent cancers that develop latently. In individuals that contract HPV when they are usually in their early 20s and the reality is for anal cancer people don't develop for instance anal cancer until the 60s, early 60s, so there's a big latency period and so that's why it's imperative to get vaccinated early on.
> Dr. Sturgis as a head and neck surgeon you obviously treat a lot of oral cancers. When did we make the HPV connection with oral cancers?
> Well this sort of started its roots back in the 90s. The first really key papers were in 1999, 2000, 2001, around that timeframe and we now looking back can see that the incidence of oropharynx cancer and for that matter anal cancer have been going up since the mid-90s and so while we saw this cancer, oropharynx cancer, was principally caused by smoking and alcohol and while we saw that with reduced smoking we were seeing a plateauing of our incidence of oropharynx cancer in the late 80s, early 90s, by the mid-90s instead of going down like other tobacco-related cancers that we see in head and neck, the incidents started to go up and so since about 1995, around that time, we've seen about a 5% increase each year in the incidents of oropharynx cancer. Anal cancer for men and for women about a 3% increase each year. Each year the incidence is 3% greater than the year before. That's a remarkable shift actually over time, that really adds up. Vulvar cancer does seem to be going up in this country as well in women and that's also an older age at presentation.
> It sounds like a looming health crisis.
> Well I think it's important that the discussion today, I know we're focusing a lot on within the state and within the U.S., but this is a global issue and so I think Eric brought up penile cancer as being an example. In the U.S. it represents less than 1% of all cancers but in parts of Asia it's up to 10% of cancers so I think that the numbers, the impact we have here really cannot only impact what we're doing in the U.S. but also impact what's going on internationally and hopefully reduce the number of individuals diagnosed as well as change the treatment paradigm.
> And I guess we have to talk about may be screening as well because you talked about a latency period. I mean people carry around HPV not knowing it and it's a ticking time bomb for some people so it sounds like how do we do that? I mean how do we approach that to find that they might have an HPV type that would cause cancer down the line?
> So I think for females obviously it's a matter of just going to see your gynecologist on a regular basis. I mean for those individuals that are too old to get the vaccination because we don't really know if there's a benefit after I believe the age of 27, then they need to see their physicians regularly. You'd be surprised how many people don't have a primary care doctor or they don't go to get their regular Pap smear and any individual, at least for a female, any individual diagnosis with one of these gynecological malignancies is still at high risk for developing a second kind of gynecological malignancy, three to five times higher risk if you've had one first and then for the development of the other. There's also linear risk associated with tobacco abuse as well.
> So Dr. Eng you're saying that some people don't even have a doctor and aren't seeing a doctor for these things. One of the goals of the moon shot I believe is to improve access to cervical cancer screening. How do you go about that?
> Let me jump in here. So Kathleen Schmeeler [phonetic] who's another one of the coleaders on the moon shot has been involved both in underserved populations in the United States, particularly the Rio Grande Valley, as well as locations in South America and in Africa in two aspects. One, in the Rio Grande Valley a program called Echo which is really a mechanism by which they are bringing sort of education to the providers in the valley for proper screening for cervical disease and that mechanism is having a lot of success in places where there is lack of access and will be expanded to places globally. We might add that in most of Africa cervical cancer is the leading cancer in women and the leading cause of cancer death in women so that effort is going to expand globally. Secondly, Kathleen is working with Rebecca [inaudible] at Rice who is developing novel technologies to make both screening, diagnosis, and point-of-care treatment easier. So in places like Africa where it may be difficult to have women coming in for annual exams or if there is an abnormality coming back in for treatment, trying to get the -- , to streamline that so that it can be done in mobile units where they can provide cervical cancer screening and treatment.
> And this may seem like an obvious question but can you test somebody for HPV, I mean can you just test anybody and find out whether they have a certain strain of HPV?
> Yeah, you can -- , well it's easiest to test the cervix and that's why it's done on a regular basis. For instance for anal cancer there's a certain technique that has to be learned and unfortunately not many people are familiar with that technique and one of the individuals that has perfected that is Joel Puloski [phonetic] at UCSF. He's an infectious disease doctor and he focuses on HIV-positive patients and precancerous patients. Globally though I would say the majority of people do not know how to screen for let's say anal cancer and there's issues also with oropharyngeal cancer. As Eric mentioned anatomically it's very difficult to reach that area appropriately to test for it appropriately so most individuals in fact won't know unless they've been diagnosed with some type of sexually transmitted disease or know of their partner having some type of sexually transmitted disease.
> You mentioned HIV, is there a connection with HIV and HPV?
> So patients that are diagnosed with HIV are actually at higher risk for getting HPV and obviously as a result they are also at risk for getting HPV-associated malignancies. HIV-positive patients actually present at a much younger age than a non-HIV-positive patient with an HPV associated malignancy and despite the use of anti-retroviral therapy in these patients the incidence is not declining in this patient population. The worst part is that currently a lot of trials exclude HIV-positive patients because of the fear that they may not be able to tolerate investigational therapies well and because it's not really clear what CD4 count is reasonable. We're trying to change that mindset and trying to include HIV-positive patients if possible on our clinical trials.
> So what are the other goals of this moon shot? Obviously outreach, public awareness and education are the big ones but are there some treatment based or treatment efficacy based goals?
> Well one last thing on the screening, a big part of the screening goals as Kathy eluded to general screening for HPV cancers other than cervical cancer is really not standard practice. There are certain high-risk populations that anal screening takes place and there is shown some success in those selected populations, but for oropharynx cancer, a cancer which develops in your mid-50s and many anal cancers which develop I think you said in your 60s, there's not a screening opportunity for individuals. Part of that relates to how these diseases traditionally have been relatively rare but as we go forward part of the moon shot effort is trying to determine are there ways in which we could screen for HPV cancer not in the HIV population so in the general population. So we have a screening trial with moon shot funds for men which will be screening primarily for oropharynx cancer but there will be a component for both penile and anal cancer and there is a trial that's in part supported through moon shot funds for women who've had either cervical cancer or high-grade cervical dysplasia which Kathy mentioned is I think three to fivefold increased risk you said for later development of anal cancer -
> Any gynecological -
> Any gynecological second cancer so they will undergo anal cancer screening. So that has to do with a couple of points we wanted to say about screening. For treatment we're starting to understand that in many ways these different cancer sites have a cancer that's essentially caused by the same thing, by the [inaudible], the molecular mechanisms by how these cancers develop seems to be very similar but we need to really rigorously explore that so Kathy is getting together the largest group of some of these rarer cancers like anal cancer and penile cancer and we're going to combine those efforts to look at similarities with cervical cancer and oropharynx cancer to see are their similarities in targets for therapy or are their similarities in genetically how these cancers look. That's for one. Number two, trials which will be available across the different disease sites are now opening up and we have one trial led by Bonnie Glisen [phonetic] and [inaudible] which will be vaccine plus, not the traditional vaccine we've been talking about earlier here but an actual therapeutic vaccine, along with checkpoint blockade for cancers that develop in a recurrent setting. And then Kathy is involved with trying to develop other trials that would be available, again both in HIV population but in the general population across these disease sites.
> And I just want to clarify for the audience that a checkpoint blockade is a form of immunotherapy?
> Correct, sorry, that's right.
> So there is a role for immunotherapy in treating these cancers.
> There may be a role, that's what we're trying to figure out, but there is also other types of treatment. That's just one component of what we're trying to evaluate and test for our various malignancies and I think what Eric points out is that for recurrent head and neck cancer there's no real home run in that setting. For metastatic anal cancer there is no standard of care established still. There are ongoing prospective trials and additional trials in the refractory patient population that I'm working on with other people. There's no standard of care honestly for locally advanced and metastatic penile cancer so we are basically --, our goals are set very high to try to help these individuals that are impacted by these HPV associated malignancies but the one thing that's quite unique I think about our HPV moon shot is it such a multidisciplinary effort that covers so many departments, so many subspecialties, and yet we're all trying to work together as a group because they are all HPV associated but yet they are all a little bit different in regards to how we would approach these malignancies.
> So in closing the typical moon shot is about a five year goal so where do you hope to be in five years?
> Well I hope to establish actually and get an FDA approved agent for metastatic anal cancer. There is currently no treatment paradigm at all for metastatic disease and for locally advanced obviously there's been no real change in treatment paradigm for about 30 years so as the subsection leader for the rare cancers we want to try to establish a standard of care for these malignancies. People used to never really think about rare cancers and honestly it's now so nice to see that [inaudible] actually has interest in rare cancers and that there may someday be an FDA indication for some of these cancers so for me that's extremely exciting.
> And for you Dr. Sturgis?
> Well I would say three things. One is that the special position that HPV vaccination has in the population or the population thought is ended and that we realize that our children should all be vaccinated for HPV. Secondly is that we develop some sort of screening mechanism that's available for low resource settings that frankly, places like [inaudible] in Africa will have an opportunity to address the problem of cervical cancer and then that the other screening issue is really that these other cancer sites, anal cancer, oropharyngeal cancer, that we come up with a novel paradigm for screening for those cancers and the therapy as Kathy mentioned is exactly the point. Can we come up with new therapies that not only allow us to offer something for these people with recurrent disease which is a disaster whether it cervical, oropharynx, or anal cancer, and can we adopt that into standard practice for newly diagnosed patients so that we can reduce some of the current toxicities these patients suffer with standard therapy.