Episode 1: HPV

Diagnostics: Beyond the Lab

On this episode we discuss the Human papillomavirus or HPV, vaccines, testing and cervical cancer. What is HPV and what is the way forward for testing?Joining us for this discussion is Larry Vaughan, director scientific affairs integrated diagnostic solutions at Becton Dickinson, one of the largest global medical technologies in the world, and Dr. Cathy Popadiuk, an OB-GYN at Memorial University in Newfoundland and Labrador, and a member of numerous committees at CPAC and other cervical cancer screening groups. 

Hosts & Guests

Janet Silver

Cameron Groome

Larry Vaughan

Cathy Popadiuk

 

Meet the Hosts/Guests

Janet E Silver

Janet has spent nearly 30 years working in news and current affairs across all mediums in Canada and the U.S. Prior to joining Syntax Strategic as Senior Director, Advocacy and Communication, Janet was the Managing Editor at iPolitics, an online news outlet focusing on policy and politics on Parliament Hill. While there, Janet led the editorial team’s daily news coverage, hosted the weekly podcast ‘No Talking Points’ and moderated/appeared on numerous panel discussions.

Previously Janet was executive producer of Global Television’s Sunday morning program, The West Block, a writer/producer for CBC’s Power and Politics and news director for CTV2 in Ottawa.

Janet spent 20 years in Washington, D.C. where she worked for the ABC Australia, Reuters, Fox News Service and various documentary companies as a freelance producer.  Janet has covered numerous political conventions, elections and traveled around the world covering news events. She also did two stints in Russia as communications director for the International Federation of Red Cross Red Crescent Societies. 

Larry Vaughan

Larry holds a bachelor’s degree in Genetics and a Ph.D. in Molecular Microbiology, both from Trinity College Dublin.  He began his career in vet vaccines, leading a molecular development team at BioResearch Ireland, based on the Trinity campus. He moved his career to the US in 1998, joining Corning’s Life Sciences Division, developing products for Pharma research.  His desire to return to infectious disease research led him to join Digene Corporation, the first HPV diagnostics company, in 2006. 

After the company was acquired by QIAGEN, he moved to his current company, Becton Dickinson, to head up their R&D assay development group. This group developed the BD Onclarity™ HPV Assay that gained FDA approval in 2018 and additional approval for extended genotyping in 2020.  He moved to Medical Affairs in 2019, as a Director of Scientific Affairs.  In his current role, he works with both clinicians and laboratorians to improve cervical cancer screening best practices and continues to play an active role in clinical studies to advance knowledge. 

He is particularly passionate about the adoption of self-collection for HPV to help eradicate the unnecessary disease that is cervical cancer.

Dr. Cathy Popadiuk

Dr. Popadiuk is an Associate Professor in the Department of Obstetrics and Gynecology, Faculty of Medicine, at Memorial University. Her search for adventure led her to Newfoundland and Labrador where she has enjoyed a fulfilling career practicing as Gynecologic Oncologist since 1998 with special interest in Cervical Cancer. 

Her passion and commitment for Cervical Cancer screening and prevention began when she visited the Sioux Lookout Zone in Northern Ontario as a University of Toronto medical student, studying Pap smear screening in the Aboriginal Women of Northern Ontario. She went on to complete her residency in Obstetrics and Gynecology at McGill University followed by Gynecologic Oncology fellowship training at the University of Toronto. Through her advocacy, she helped create the Cervical Screening Initiatives Programme in Newfoundland and Labrador and has been its Medical Director since 2003. She was the Clinical Lead for the Canadian Partnership Against Cancer Oncosim HPV Cervical Microsimulation Model which assesses the effects of various screening and preventive strategies on cervical cancer outcomes in Canada.

She has been on the board and executive of the Association of Academic Professionals in Obstetrics and Gynecology in Canada, and the Society of Obstetricians and Gynecologists in Canada, helping lead the merger between the two organizations in 2019. She is also the Chair of the Canadian Foundation for Women’s Health, a charitable organization that advances the health of women through research, education and advocacy in obstetrics and gynaecology.

During her tenure in Newfoundland and Labrador, she completed a Master of Business Administration at York and Northwestern Universities, and a Master in Studies of Law at the University of Toronto.

Dr. Popadiuk enjoys participating in a broad spectrum of research and education endeavors, including receiving a patent for a novel biomarker for cancer progression, to reaching wide audiences through digital and print media and academic literature.

About This Episode

[00:00:00] Janet Silver: Hello, I’m Janet Silver from Syntax Strategic. 

[00:00:10] Cameron Groome: And I’m Cameron Groome from Microbix Biosystems. Thank you for joining us for Diagnostics: Beyond the Lab. On this podcast series, we talk to industry leaders in the scientific and health community about discoveries, challenges, and what they see is the way forward in their fields.

[00:00:29] Janet Silver: Cameron I’m really excited about today because we’re going to talk about the human papillomavirus or HPV: vaccines, testing, and cervical cancer. And on the latter, according to the Canadian Cancer Society, over 1400 women across the country will be diagnosed with this kind of cancer this year alone. 

[00:00:48] Cameron Groome: Quite right, Janet and well the HPV vaccines target HPV types that most commonly cause cervical cancer, they’re neither, certainly not mandatory, and they don’t protect against disease from all possible oncogenic or cancer-causing HPV types. So, we always have to ask ourselves, you know, what does this mean? And where do we go from here?

[00:01:12] And joining us now to break all this down is Dr. Larry Vaughn, Director of R and D Scientific Affairs, Integrated Diagnostic Solutions at Beck Dickinson, which is of course one of the largest global medical technology firms in the world. And we’re very pleased to have Dr. Cathy Popadiuk, an associate professor of obstetrics and gynecology from Memorial University in Newfoundland, and a member of numerous leadership committees at CPAC and other important cervical cancer screening initiatives. We thank you both for joining us. 

[00:01:48] Cathy Popadiuk: Thank you. 

[00:01:49] Larry Vaughn: Thank you, and hello.

[00:01:53] Cameron Groome: Good. Well, why don’t we start with talking a little bit about what HPV is, the human papillomavirus and talking about a bit of its health consequences. 

[00:02:05] Cathy Popadiuk: Thank you. Why don’t I start then? The human papillomavirus has actually been around for millennia, forever, well before us, and there are lower risk types and high-risk types.

[00:02:17] And the low-risk types we’re very familiar with, they cause warts. The regular warts, and for the purpose of our discussion today, we’re interested in genital warts. The high-risk types also can cause trouble. They can get into cells. Get into the DNA embed in there and over years, go on to develop pre-cancer and cancer in some people. And that’s what we’re interested in today, preventing those high-risk HPV types from causing problematic pre-cancer and cancer. 

[00:02:51] Janet Silver: Kathy, you, you talked about prevention. Sorry, Cameron. I just want to jump in if I may, because both of my children have been vaccinated with the HPV vaccine. So, when you’re talking about prevention, what does that vaccine mean, and does it really protect them?

[00:03:12] Cathy Popadiuk: Well, we’re very fortunate because many years ago, about 1996/97. It’s been that many years, or 2006/07. We had the development of HPV vaccines, a number of them. And they include HPV 16 and 18 types, which are considered high risk HPVs that can go on to cause pre-cancer and cancer. And some of them also cover HPV 6 and 11 which cover the lower risk types that can cause genital warts. More recent vaccines, the non valent, the nine valent also cover five more high risk HPV types. The high-risk HPV 16 and 18 cause 70% of cervical cancer and many of the pre-cancers. The newer vaccines that cover up to seven high risk types of HPV can prevent 90% of cervical cancers.

[00:04:05] And very importantly, I don’t know if your children are boys or girls, but boys can be affected by HPV pre-cancers and cancers. Everyone can be affected by the pre-cancer and cancer in the anal skin, the head and neck, HPV 16 can cause cancer and pre-cancer there. For women, we can have problems in the vagina and outside on the vulgar skin, and men can be affected by penile pre-cancer and cancer.

[00:04:34] Cameron Groome: So, these vaccines have the opportunity to prevent the development of infection, precancer, and cancer in these conditions. So, they are very, very efficacious and those who’ve been vaccinated before being exposed to these HPV types, which often means before sexual debut, in adolescence and teens. These are great points, Kathy, and you, you touch on the diversity of types of the HPV virus, and maybe I can ask Larry to supplement that. You know, based on how many types there are, we’ve got these progressing vaccines that cover more types. But is screening and testing still necessary, Larry, in light of these vaccines? 

[00:05:19] Larry Vaughn: Yes, it is. And despite the fact that these vaccines are highly efficacious there are a couple of factors that mean we’re really going to have to keep screening for decades to come.

[00:05:27] The first is even in a highly vaccinated country, and we’re not one of the most in North America here, but certainly in Australia, or the United Kingdom, 80% or so is the highest you’ll get. We’re in the fifties to 60% pre covid down here in the US. So, we have a gap there. Secondly, there’s a time lag when most, as Cathy was pointing out, most vaccines are delivered to young kids around 11 or so of age. And that takes another 10 to 15 years for them to get into the age-appropriate screening pool. So, you have that gap to cover. So, we’re now seeing the benefits of the 2006, the vaccine that Kathy mentioned in the clinic today. We will need to wait until about 2030 for the nine valent vaccines to have an impact in the clinic.

[00:06:06] So we’ve got that gap. And finally, even with the nine valent, it’s 90%. So, there’s still a 10% cancer attribution out there that we need to cover. So, we definitely don’t want to take our foot off the gas on screening. And I would add, and I’m sure Kathy would agree, since Covid, there’s more urgency around that on both the vaccination side and on the screening side. Because we’ve had a serious dip in both of those areas. 

[00:06:28] Janet Silver: I just want to back up for a second, we’re talking about screening. Kathy as a woman, I’ve had a number of pap smears. How is that different from an HPV test? 

[00:06:41] Cathy Popadiuk: Well, as we’ve heard, a number of countries in the world are arguably ahead of Canada in our vaccination rates. There’s a difference across the country. I’m presently in Newfoundland, and we’re very proud of our vaccination rates. They’re about 94% for our school-based programs. I also didn’t comment that there’s efficacy from these vaccines. Even in older people who’ve been exposed, there still is benefit but not as good. 

[00:07:07] For women, pap smears are done, you know, every three years. And you know, you go and have a speculum exam and you have the test done, and then the cells are looked at under the microscope and the technician or the pathologist looks at the cells. And by then there are changes already there, that could be pre-cancer or cancer. And that’s done every three years. 

[00:07:30] An HPV test is looking for the virus. The virus, whether it’s present, has it been there for a while to get in the cells? And by being positive for the virus, it picks up more opportunities for cancer and pre-cancer. So it picks up things earlier before they are in the cells. It identifies more women and the test, if you have a negative test, the durability, the confidence you have, that there isn’t a problem and there won’t be a problem, is five years. And that’s more confidence for women than having a pap test every three years because we know that the durability, the confidence that you won’t develop a problem with a cytology pap test is only three years, but the woman receiving the test will feel exactly the same thing. You’re just taking a sample during a speculum exam from the cervix.

[00:08:32] Cameron Groome: Well, I think, you know, that covers a bit of the interval issue that we should touch on. The migration of moving from looking for cells that have been transformed by the virus, to looking upstream for the presence of the virus should be intuitive for everyone . But maybe I can ask Larry a little bit, if you’re doing an HPV test that screens for the different types of HPV, we mentioned some of the high-risk types that are covered by the vaccine, but how many types of high-risk viruses are there? Maybe you can speak to that, and about the different sites in the body that can affect it as well.

[00:09:07] Larry Vaughn: Sure. Well, generally speaking most people say there are 14 high risk types. I mean, there’s been some fine tuning over the last two years where Type 66 is kind of being downgraded, but generally speaking, all the assays have 14 high risk types in them. So those are the ones that can persist and cause invasive cancer over time.

[00:09:25] In terms of other sites, I mean as, as Kathy you mentioned in introduction, we have, you know, penile, anal cancers and head and neck cancers. I think the two most active areas of research are moving to guidance now are for the head and neck space and for the anal cancer area. For head and neck, I mean there really, there’s an epidemic now of head and neck cancer, particularly in white males, where we’ve seen a huge uptick in the number of HPV related cancers in recent years, and it’s now surpassed several years ago. The incidence of cervical cancer. So, I saw some numbers where, you know, there are about the same number of people dying of head and neck cancers now as there is of entire diagnosis of cervical cancer. So, it’s about three, four more. 

[00:10:07] So we have a serious issue there, and I think we’re starting to see some, not quite guidance in the sense of as we have for cervical cancer, but there’s certainly a lot more research and there’s testing going on, as Kathy will tell you. It’s actually, ironically, better to have an HPV related head and neck cancer. The prognosis is better and there’s testing going on that they want to identify if it’s alcohol or tobacco or HPV and there are different, there’s de-escalation of therapies if it’s HPV related. But it’s still a very serious cancer and it’s a high mortality rate.

[00:10:36] Cameron Groome: And testing, the need to test certainly isn’t going away for cervical or head and neck. Right. 

[00:10:43] Larry Vaughn: And for, just to finish up on the head and neck, it’s a lot of tissue testing. There’s a little sample type difference there was a big study in the US, just published in June, called the Anchor Study, which really showed that for an anal cancer has kind of very similar pathophysiology to cervical cancer. There’s an anal pap, which has degrees of progression, like you have for cervical. So, there’s a pathway there to both diagnosing from an anal pap side and also from HPV test site. So, we expect to see guidance in the US very shortly now that they’ve shown that you can actually drive down the anal cancer rate by treating high grade disease, pre cancer. So that’s very encouraging. 

[00:11:20] Cameron Groome: And what about, what about access to care and access to family doctors, OBGYNs by community? Certainly, we see in Canada, for example, a lot of patients have difficulty finding a family doctor. Is this an issue in this area, Larry? And by extension, Cathy. 

[00:11:37] Larry Vaughn: Sure. I mean, even pre Covid about one in five US women never got screened or were not screened on time. So that’s a serious problem. And actually, the numbers reflect that over 50% of all diagnosed cancers are in that 20% of women who don’t show up with screening. So that is a, is the problem statement right there. And that’s, as I said, gotten worse with Covid. We have a huge reduction in the number of screened women and a backlog now that we will not be able to catch up, quite honestly, unless we do something differently. So, there is, there is a real concern there. 

[00:12:06] Cathy Popadiuk: No, I totally agree that the biggest issue, it’s not necessarily the screening test, but to be able to avail of being screened by someone, and access to care providers right now is a huge challenge, in my province, across the country.

[00:12:25] People can’t access a primary care provider right now, and this is not something at this time that we can do over a telephone or a virtual visit. Pap smears, testing for cervical issues has to be done in person and it takes time and human resources, and this is a huge challenge everywhere right now for us in Canada.

[00:12:49] Janet Silver: This brings up, Cathy, the whole idea of self-collection. How important would self-collection be for women? And how would it change, if you will, or shift what we’re seeing now? 

[00:13:04] Cameron Groome: And even what we mean by the term, would be important to explain. 

[00:13:08] Cathy Popadiuk: Right. Very true. Because a lot of people don’t understand what self-collection is.

[00:13:13] They might think that one can get a blood test or do a swab of the throat looking for HPV for the cervix, but nope. Still need to take a sample to self-collect from the cervix inside the vagina. So, it means using a tool. So, some women are more facile with tampons their own, you know, personally understanding their lower jungle tract. Other women might find it taboo to explore down there. So, it’s definitely the demographics of women who would be able to avail of a test where they could use a tool, be it like a little Q-tip. There are like flock swabs and tools created, to be able to get close to the cervix personally, to take the sample and then to put it in appropriate packaging and send that off for an HPV test.

[00:14:08] It cannot be a cytology cell path test where someone is going to look at it under the microscope. There is no self-testing of cytology tests that would be for a molecular, like an HPV test. So, there are opportunities to use this type of technology where we haven’t been able to allow women to self-sample.

[00:14:30] Right now in Canada, there is no actual self-sampling program or testing. There are a number of pilots that have been done across the country showing that a proportion of women would want this. They’re comfortable with this and then they can follow up for an examination for someone to see their cervix as needed, if needed, depending on the result.

[00:14:56] So this is work in progress. It’s really exciting. We believe it will be very helpful for women who are unable to avail of a care provider or just are in circumstances that they’re too busy and their time commitments, they can’t go out to a clinic, there isn’t a clinic and that they can have a test done to look for potentially, HPV that can cause pre cancer in cancer.

[00:15:23] Cameron Groome: That’s, that’s a great explanation Cathy. I know, Canada, the first provinces are just starting to get ready to provide molecular HPV screening programs. Self-collection is, is some way away, some other areas of the world are more advanced on that. And, and maybe I could ask Larry to comment about what BD is thinking and doing in this respect. 

[00:15:45] Larry Vaughn: Yeah, it’s absolutely right to say that we’re a little, a little behind, I think, in North America, but I think we have a plan to catch up. But right now, the self-collected devices are CE marked, several available in Europe. So, we have a number of choices of devices. They’re now being implemented into national screening programs such as Denmark and Sweden and others. Australia added that. Initially it’ll be added at the clinic. 

[00:16:05] But just to explain, that’s even by itself, that’s a huge add on because, as Cathy mentioned, a lot of people have difficulty getting to a GP or even OBGYN who does a pelvic exam. This does not require a pelvic exam, could be done in the bathroom of any clinic, you know, local provider. So that just expands the umbrella of coverage immediately by allowing that approval. The other thing, of course, the end game with self-collection is to be able to ship the kit to the home. And we now have good data on, and this is what we call dry collection. So, there’s no liquid sent to the home. That simple brush, device, or swab, as Cathy mentioned, can be used and the woman just simply self-collects, puts that in a container, puts it in the mail and the lab then takes it from there and processes the sample.

[00:16:51] And a lot of data now meta-analysis and randomized control trials show that if done properly with an approved test, it’s just as effective. It’s what we call non-inferior to the physician sample in terms of sensitivity. So, we’re already seeing that in places like Denmark they initially offered it to underserved women, women who were not showing up for screening. They obviously picked up more cases there, and then they extended it to, as an alternative to women who are indirectly screening programs. And not surprisingly, ladies, you would agree that it’s a nice option, so they like to take that option. And what they find is that not only, they do it, but they request it the next time. So, it will expand coverage. And I think in five to 10 years, once it’s adopted, it’ll become like a pregnancy test. It’ll be freely available; it’ll be the first line test. And then the woman would come into the clinic or to do our OBGYN, our physician, for a follow up on a positive test. So, I think that’s the future, and it’s going to come quickly so we can talk about the US in a bit. 

[00:17:44] Janet Silver: Can I just interject for a second, because you’re talking about self-collection and a woman being able to do that from her home. But Cameron, I know that Microbix has a lot of experience in this area in terms of accuracy and from a layman’s point of view, how do you ensure that whatever you’re collecting, that the test is accurate, that the controls are there, that you’re not going to find yourself getting a false report if you will?

[00:18:10] Cameron Groome: Well, you’re raising a great point, Janet. And there are internal controls that are built in within tests like those by Beck Dickinson that ensure that the instrument is functioning properly. Where we really step in and take a role is in the whole process of what are called external controls.

[00:18:27] So you need to make certain that the whole process of, you know, will this sample survive the mail and the heat? Will a technician be doing the steps in the right order? Will the reagents not be spoiled? Will the instrument not drift out of calibration? So, there’s a regular process of challenging with a representative mimic of a patient sample to ensure the length of that whole process, and that’s where Microbix plays a role in all this. In period, regularly challenging the whole test process to make sure there isn’t any breakdown in the integrity of the process. And you can’t overstate what an advancement this is, to move from detecting cells that are already transforming or been transformed into cancer versus looking five or more years upstream to those at risk. But it has to be done properly and be regularly revalidated. 

[00:19:25] Janet Silver: I know we only have a couple of minutes left, so, and we’ve probably got something that we would like to ask each one of you, but Cathy, I’ll throw it to you first. We’re talking about self-collection. How, if we’re able to get down to this road shortly in Canada, how would that impact testing in Canada?

[00:19:43] Cathy Popadiuk: Well, as we heard, it probably would be able to be offered to women who can’t access a healthcare area, a clinic, and it could be mailed. And certainly, in Newfoundland, we’ve done studies on that. Northern Ontario, BC is leading the country in studies of mailing back your sample. For fit testing, for colorectal screening we’ve heard about that. The public is used to that and that will potentially fill a void of women who can’t access to do a test and want to. So that is very, very helpful. And we also heard some women just, you know, they might need some guidance, and you could also do it in a clinic. And that would also potentially increase the number of people who could be tested in clinic environments. Where some could be going through a speculum, the formal procedure with a healthcare provider, and someone could bring their self-collection kit if they needed some extra guidance also there. There’s a whole, vast array of opportunities where it could be integrated into what’s already happening to increase the number of women who can be able to be screened. That’s the most important thing.

[00:20:56] Cameron Groome: Fabulous. Larry, what points would you want to touch upon with regards to the work that you’re doing and making sure we’re covering the appropriate number of HPV types, helping ensure that those tests are optimally accurate as well? 

[00:21:11] Larry Vaughn: Yeah. Well, I think we know what the types are that cause cancers. We know one of the great things about cervical cancer is we know exactly what to do, but the question is implementation, right? So, I think self-collection will be a huge add-on to a robust kind of vaccination program. I can see it being used. You know, persistence is the main cause of disease. So persistent infection of the same type is really what gets women in trouble if their immune system doesn’t clear it. So having the ability to add the self-collection to a regular screened woman, who she’s coming, “come back and I’ll send you a kit in six months”, it really provides more information without having to bring her back in.

[00:21:46] So I think that’s important, but coming back to your direct question, having that internal control knowing that the woman collected it correctly, and having the qualified assay is gonna be key. And again, we’ve already demonstrated this in other national programs, so we do know what to do. I think there just has to be a will to get it done and to expand testing. 

[00:22:04] And again, to come back to covid, I am concerned that we will see an uptake. We’re already seeing an uptick in disease in the clinic. I talked to a clinician the other day, he said, “I’m doing more colposcopies, I’m seeing high grade disease.”. This wave’s already here. And we also have the add-on of those kids who didn’t get vaccinated who are going to be, further down the line. They’ll be showing up in the clinic as well, without the adequate coverage. So, we do need to act now, I think, and, and get self-collection rolled out to these people.

[00:22:31] Cameron Groome: Missed medical appointments, missed vaccines, and the hangover of that from, from covid.

[00:22:37] Larry Vaughn: Sure. Yeah, exactly. 

[00:22:38] Cameron Groome: Well, certainly, you know, we are also looking at providing services to assist different provinces and different jurisdictions in their implementation of HPV molecular testing and having not just the products, but also the services to help support these great initiatives.

[00:22:56] Cathy Popadiuk: Following up on what Larry said, people have been sitting at home not being able to avail of any healthcare, and these tests that we’re talking about are not a substitute, be it if you can access self-collection or so on. If a woman has symptoms, pain, bleeding, discharge, other problems. That’s not a screening test, she has to be seen by a care provider. So, I don’t want the audience to think that these tests are a replacement when someone actually has symptoms. This is for the well population. You know, it’s exciting, but we have a lot of work ahead with Covid. 

[00:23:33] Cameron Groome: No, substitute for primary care.

[00:23:36] Cathy Popadiuk: Right.

[00:23:37] Larry Vaughn: Correct. 

[00:23:38] Cameron Groome: Great point. 

[00:23:39] Janet Silver: Larry Vaughn with Becton Dickinson based in Maryland, and Dr. Cathy Popaduik from Memorial University in St. John’s. This has been a great discussion. 

[00:23:48] Cameron Groome: Thank you again, Cathy, Larry, and Janet. That’s all the time we have for today and look forward to the next webinar in our series. Thank you. 

[00:23:58] Larry Vaughn: Pleasure to be here. 

[00:23:59] Cathy Popadiuk: Thank you.

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