Winning Against HPV

TRANSCRIPT:

(theme music in)

Dr. Charles Ryan: This is The Good News About Cancer. I'm Dr. Chuck Ryan. 

Dr. Alicia Morgans: And I'm Dr. Alicia Morgans.

Chuck: We're oncologists, and we've spent our careers working to understand cancer. We believe that there's more progress now in research and treatment than there ever has been. And we're here to share that with you.

Alicia: In each episode of this show, we talk to one of our colleagues about a new development in cancer treatment or diagnosis. We'll break down what's new, why it matters, and how it points the way forward.

Ashish Deshmukh: If we're able to get 80% HPV vaccination rates, we would have substantial community protection to be able to completely eliminate HPV-associated malignancies.

 (music out) 

Chuck: Alicia, so you have a bit of a background in public health – I know that you have a master's in public health. So hopefully this isn't too challenging of a question for you. But what is HPV and why does it cause cancer?

Alicia: You know, I love that this is really taking on a public health topic. So human papillomavirus, or HPV, is a virus that's been circulating through people for who knows how many thousands of years, I'm sure. And it causes cancers. It causes things like cervical cancer, anal cancer and even some head and neck cancers.

And I think that when we think about public health crises, we often think about things like COVID and flu as caused by viruses. But we don't always think about these kind of downstream things that can happen when you get a viral infection and you clear it, or you and you don't even know you have it in the first place. And you know, 10 years, 20 years later, it causes cancer. 

So HPV vaccination came out, I remember, when I was a resident. And we were vaccinating young people at the time and it was so interesting – and actually kind of upsetting to me because I was too old already to get vaccinated. But I was really excited to hear that we were going to be vaccinating people and preventing this virus that can cause all these cancers, and at least prevent some STD transmission in young people.

So, you know, that's what was happening when I remember hearing about HPV vaccination. You know, what do you think about it? And why did you think it was important to bring this particular story to our attention?

Chuck: So back when the vaccine first came out, as you said, you know, we were excited that it was going to maybe lead to prevention of death from cervical cancer. Well, now we've got the answer. So I was excited that we have the first data on survival from the generation of people who could be vaccinated. That's the point, right? 

Now we've got an epidemiologist who is able to track these numbers. And I think these are underappreciated heroes of our health system. The people who track disease and trends and all of that is a field called epidemiology. This was somebody, Dr. Deshmukh, he's an associate professor of public health sciences at the Medical University of South Carolina. Never met him before. But, as it turns out, I was on Blue Sky one day and, as we like to do, we post– he posted a paper on Blue Sky, and it gave this amazing statistic about the decline in mortality from cervical cancer. So, I messaged him right away, said, “Hey, I'm starting a podcast and would love to interview you.” 

Now, what's amazing is that Dr. Dushmukh's paper focuses on mortality in people under the age of 25, which is like this early group of people who, if they weren't vaccinated, could be at risk for not only getting the virus, but getting the cancer and then even dying of the cancer at such an early age.

Alicia: Well, let's get started and hear about another way that vaccinations can help us – in this case, even preventing cancer. 

 (music) 

Chuck: Why don’t you start off by telling us a little bit about what your most recent findings are and their significance. 

Dr. Ashish Deshmukh: So it has been 16 years since the initial approval of HPV vaccination. And vaccination rates have improved in the U.S. If you look at one-dose HPV vaccination coverage in most recent years, it's close to 78, 79%. 

So what we wanted to see is that– the first cohort of young women who received HPV vaccination, they now have entered the age group where we might see benefit of HPV vaccination in terms of cancer prevention and reduction in cancer mortality.

So, we quantified cervical cancer mortality, or death rate, in the youngest age group, women who are less than 25 years old. And we observed that, starting from 2013, there was 62% reduction in cervical cancer deaths, in this cohort.

Chuck: Let's take a moment and talk about HPV. Can you explain it, what the virus is, what types of cancers it can cause, and what is the vaccine?

Ashish: Sure. 

Chuck: The basics.

Ashish: So human papillomavirus, it's the most common sexually transmitted infection in the United States. There are more than 200 known strains or types of HPV. But there are two or three strains that are key and they're important for us, because HPV type 16, 18 are responsible for causing most cancer cases. The virus itself is responsible for causing six cancers, and it causes cancers among both men and women.

Now, in the United States, if you look at cumulative burden of HPV-associated cancer – so a collective number of HPV-associated cancer cases – we have nearly 45,000 HPV-associated cancer cases in the U.S. Among women, oropharynx cancer is the most common HPV-associated cancer. The other types that HPV causes are cervical, vaginal, vulvar cancer among women. Among men, it causes penile and oropharynx cancer. 

Chuck: So a vaccination, the timing of the vaccination leading to the prevention of the cancer and then leading to the prevention of the cancer death is what? Tell us a little bit about the timeline between, you know, what you would expect for the disease to take.

Ashish: Right. So when we think of cancer prevention and prevention of cancer deaths, it's truly a sequential process. Once someone gets the HPV vaccine, what the vaccine essentially does is that it prevents infections that would ultimately lead to cancers. 

So in our previous studies, we have documented that in the most recent generation of adolescents, young female HPV infection rates have dropped from 13% to 2%. So that drop occurred in [the] early 2010s.

We published another study in 2011 where we showed that as a result of infection decline, the youngest age group also saw reduction in cervical cancer incidence. So, starting from 2012, cervical cancer incidence rates declined 12% per year in this first generation of young females. And what we're observing now is that when we think of sequential impact of HPV vaccination, it first led to reduction in infection prevalence, then incidence of cervical cancer. 

And now, the hypothesis for us was truly whether, when we think of cancer mortality, it follows cancer incidence. So whether reduction in cancer mortality would have followed reduction in cancer incidence. And that's exactly what we observed, that mortality rates declined following reduction in cancer incidence.

Chuck: So, in other words, for a person to sadly die of cervical cancer based on this, it would require that they, A) get infected, B) that not all who are infected ultimately get cervical cancer – I think that's an important thing we need to clarify – and then, C) once the cervical cancer has started or has begun, there's a risk for mortality that can take place several years later. 

You said that the infection rate dropped from 13% to 2%. Is that all due to vaccination or is it due to changes in sexual practices, et cetera?

Ashish: So, when we looked at infection prevalence across calendar years and among different birth cohorts, the women who were born in 1980s versus those who were born in 1990s, what we are seeing is that infection rates dropped among those who received [the] vaccine and those who did not receive [the] vaccine.

So, reduction in infection among vaccinated cohorts is truly because of the direct benefits attributable to HPV vaccine. But among unvaccinated young females, infection rates are dropping because of herd immunity.

Chuck: Okay. Okay. Tell us a little bit about herd immunity. We've heard that term before, I think, probably in the context of COVID. But this is a different setting. So tell us a little bit about what that is.

Ashish: So, herd immunity, it's truly a population-level phenomenon where, if certain proportion of individuals in the population are vaccinated, what that would do is: because HPV transmits from one individual to another, and because we're reducing infection prevalence at the community level, we're also indirectly averting the possibility that the transmission of infection will occur from individual to individual.

So even if someone is not benefited, they'll not acquire HPV infection because of this community-level protection. So what we are truly doing by improving vaccination rates is that we're achieving greater community protection. 

And that's exactly what has happened in the context of HPV infection and cervical cancer. That [a] certain proportion of adolescents are benefiting from HPV vaccination as a result of community immunity.

Chuck: Fascinating. So, to parents out there who are listening and saying, well, I only have boys, this doesn't apply to me for my children, what's the response?

Ashish: Boys, in fact, when we think of oropharynx cancer, anal cancer, penile cancers– all these cancers are on the rise. And oropharynx cancer affects more boys, now, than cervical cancer affects girls. It's the cancer that's most common and it's rising rapidly. So we need to be caring for our boys and ensuring that they receive the HPV vaccine. 

Chuck: Right. It’s really more than just a cervical cancer vaccine. But cervical cancer appears to be the first and really the most dramatic decline in mortality that we’ve seen to date, correct?

Ashish: And the reason for that is, cervical cancer occurs early on in the life. Other HPV-associated cancers, they occur among individuals who are in their 40s, 50s, and 60s. They are associated with aging. So the first impact that we are seeing is, is truly– as a result of HPV vaccination – is the decline in cervical cancer. 

Chuck: And this was achieved with about a 78% rate of vaccination. So young women eligible to be vaccinated, you said previously 78% are vaccinated. What's it going to take to get to 100%? And do we need to get to 100% to continue to see a decline? What are your projections moving forward? 

Ashish: The coverage that I mentioned was greater than equal to one dose of HPV vaccine. But what's important is the way HPV vaccinations are administered or recommended. If someone is less than 15 years old, they're required to get two doses of HPV vaccination to be up to date on their schedule. And those who are 15 years old or older, they're required to get three doses. Individuals who are immunocompromised need three doses of HPV vaccination.

And when we look at up to date rates of HPV vaccination or coverage, in the U.S. we are currently at 60%. Now the healthy people have established a goal that it's important to achieve 80% HPV vaccination rates, and we know that that is an optimal coverage. 

If you're able to get 80% HPV vaccination rates, we would have substantial community protection to be able to completely eliminate HPV associated malignancies in the future years.

Chuck: I'm just going to restate that because that's a fairly profound statement. If we as a country vaccinate 80% of the eligible recipients, we should have optimal coverage to eliminate HPV-associated risk of cervical cancer death. 

Ashish: Not just cervical cancer, but five other cancers that HPV causes.  

Chuck: So, can we talk a little bit about the history here? If you go back, we were talking about prevention of cervical cancer, but cervical cancer early detection, dysplasia detection, is really also a great public health story, right? This goes back to the pap smear, which, if I'm not mistaken, I think started in the 1960s. Can you tell us a little bit of the story of the screening?

Ashish: I mean, when we think of cervical cancer prevention, first it's one of the handful of cancers that are preventable, truly. When we think of cancer prevention, we either have early detection where the objective is to identify cancer early on, at early stage, but cervical cancer, colorectal cancer, anal cancer are three cancer types that we can truly prevent even before their occurrence.

So the idea of screening is to detect pre-cancerous lesions or pre-malignant lesions – we call it a pre-cancer – and treat them so that we can prevent the occurrence of cervical cancer. 

Cervical cancer screening was initiated in 1960s or 70s. And as a result of the initial success of cervical cancer screening, it's widely implemented in the U.S. Cervical cytology was the first tool that, that we had– 

Chuck: This the pap smear, to be clear. 

Ashish: This is the pap smear test, where it allows us to identify those pre-malignant lesions and then the objective is to treat them. But screening has evolved and now we have superior tools. We have high-risk HPV testing, which is more sensitive, more specific.

And it allows us to identify a pre-cancerous lesion, and at a population level, it's a superior test because it would prevent more cancers, compared with cervical cytology, pap smear.

Chuck: So the pap smear is really a test to, to look at the effect of the pre-cancerous lesions or to, to detect the pre-cancerous lesions that if, left untreated, will lead to cervical cancer. And so that's somewhere between a prevention and an early detection strategy, I think.

Ashish: Isn't it amazing that cervical cancer is the only cancer for which we have both primary prevention and secondary prevention? 

Chuck: Oh, good– well-put.

Ashish: Both through HPV vaccination and screening.

Chuck: Right. So you can prevent it with the vaccine. If you have the early lesions associated with it, it will be detected on a pap smear. So vaccinated women still need to get pap smears, correct?

Ashish: They do. Because we truly don't know if they have already acquired the infection, pap smear would ensure that we have complete assurance that they'll not develop cervical cancer. 

Chuck: So you're a public health investigator, a public health researcher. Tell us a little bit about how you got into this work and what drives you.

Ashish: So I'm a cancer population scientist. I'm trained as a health services and health outcomes researcher and decision scientist. But early on in my career, when I was doing my PhD, I was working with a mentor and I was looking for projects at that time. 

He came up with four or five different projects. It's– I still remember, it's almost 10 years now. And he said, which project would you be interested in? And there was something that really caught my attention. It was anal cancer screening. 

So, when I was growing up, I lost my grandmother to anal cancer. And I had a personal connection with that. I thought, why not study anal cancer? Without knowing at that time that it's caused by HPV. So, I started studying anal cancer, anal cancer screening among women living with HIV. And while studying anal cancer, I started learning more about HPV and six cancers that HPV is responsible for. 

So, throughout my career, I have been studying HPV associated malignancies from a health services, health outcomes, standpoint of view, but cancer epidemiology is very close to my scientific heart.

Chuck: We've crunched a lot of numbers, but for those who have lost track of the numbers, what's, what's the positive outlook you can give to the listeners on this story?

Ashish: Sure. So I would truly think of this study as the initial foundational success story of HPV vaccination. Imagine, we have the first birth cohort of young adolescents who have received 62% reduction in cervical cancer mortality as a result of HPV vaccine. 

And when we think of [the] majority of burden of HPV associated cancers – when I say burden, that means number of cases – there are currently individuals who are in their 30s, 40s, and 50s.

So this is an initial premise of what may come next if we continue to improve HPV vaccination rates. 15, 20 years from now, imagine we can prevent 20-25,000 cases of HPV-associated malignancies as these birth cohorts are aging. 

So to me, I think it's, it's, it's an important success story of the HPV vaccination. And we'll continue to see improvement provided that we continue to do our best to ensure that HPV vaccination coverage stays on track towards that 80% goal.

Chuck: Dr. Ashish Deshmukh of the Medical University of South Carolina. Thank you so much for your time today. Thank you so much for dedicating your career to this really, really important work.

Ashish: Thank you so much, Chuck, for covering our study. It was truly a pleasure to speak with you and I hope that it would help spread more positive impact and message about HPV vaccination.

 (music) 

Alicia: Another great conversation. Really, really excited to hear about how we are making such strides, not only in stamping out this virus, but also in stopping cancer, stopping cancer deaths. Thank you so much for bringing this one to our attention and having such a great conversation with Dr. Deshmukh.

Chuck: Yeah, it was great getting to know him and hear this data. And the amazing thing also is, focusing on young people, and the decline in mortality as he did, these results are going to amplify over time. If you see a substantial reduction of over 60% in mortality by the age of 25, imagine what it'll be by the age of 50 in these people. So we're talking about many, many additional years of healthy life lived. So great progress, good news about cancer.

 (music) 

Alicia: Thanks for listening to The Good News About Cancer. I'm Dr. Alicia Morgans, a medical oncologist at Dana Farber Cancer Institute in Boston.

Chuck: And I'm Chuck Ryan, also a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. Thanks to Lilly for support of the show. 

Our production partner for this series is CitizenRacecar. This episode was produced by Anna Van Dine with post-production by Jose Miguel Baez.

Alicia: And there's a whole lot more good news to talk about. So make sure you subscribe to this show wherever you listen to podcasts. And if you like the show, share it with someone you think might find it interesting. 

We'll be back again soon with more good news about cancer.