This Podcast Will Kill You - Ep 67 HPV: My wart be with you

Episode Date: February 23, 2021

The world of human papillomaviruses is vast and varied, and causing cervical cancer is just one of the many roles these viruses can take on. From their carcinogenic tendencies to their more benign wart-forming ways, this episode explores what these tiny viruses have taught us about how our bodies prevent cancer, how imaginative old timey cures for warts can be, how slow acceptance of the facts and a failure in marketing led to a delayed and impaired vaccine uptake, and so much more. You could say we’re covering all aspects of this highly-requested topic, warts and all. The historical stigma of cancer as a “woman’s disease”? Check. What’s actually inside a wart? Check. The possible origins of a mythical creature? Check. The massive disparity in vaccine access between high- and low-income countries? Check. Tune in to hear it all. See omnystudio.com/listener for privacy information.

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Terms and Conditions Apply. Visit blueapron.com slash terms for more information. I'm Clayton Eckerd. In 2022, I was the lead of ABC's The Bachelor. But here's the thing. Bachelor fans hated him. If I could press a button and rewind it all I would. That's when his life took a disturbing turn.

A one-night stand would end in a courtroom. The media is here. this case has gone viral. The dating contract. Agree to date me, but I'm also suing you. This is unlike anything I've ever seen before. I'm Stephanie Young. Listen to Love Trapped on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts.

This is Special Agent Regal, Special Agent Bradley Hall. In 2018, the FBI took down a ring of spies working for China's Ministry of State Security, one of the most mysterious intelligence agencies in the world. The Sixth Bureau podcast is a story of the inner workings of the MSS and how one man's ambition and mistakes opened its fault of secrets. Listen to the Sixth Bureau on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. My name is Stephanie. I am 34 years old, soldier with the U.S. Army and also a government contractor. In 2016, right when I became a single mom of my two daughters, I went to get a... pap smear. I had only missed two pap smearers before that and didn't think anything of it.

The exam itself went as normal as possibly could be. It wasn't until about two weeks later that I got a call from the gynecologist herself urging me to come in as soon as possible. She offered to waive any co-pigs and schedule me in between clients because she said it was absolutely urgent that I went in there. So I went in the very next. next day and she called me into her office and sat me down and I remember mostly how happy and cheery she was in what I knew was going to be very bad news. She took out a paper and started with don't panic, but we found cancer cells in your cervix. And she explains that I had adenocarcinoma in situ or AIS and explained to her.

me that although they're considered pre-cancer cells, the type of cancer itself at no carcinoma tends to jump membranes quicker than the other type of cervical cancer, just squamacel carcinoma. And she told me that I needed to schedule an appointment with the gynecologic oncologist at the hospital down the road. And the whole time she kept telling me not to worry that this was good cancer and that I am one of the lucky ones. I scheduled the appointment afterwards to go to meet the oncologist. And when I did meet him, he said the same thing. He says that I should feel very lucky and believed that this is good cancer and that they were going to watch me for a few months and scheduled me for a cold knife conization biopsy. In those couple of

months, I had to basically learn how to deal with the possibility of having good cancer as opposed to bad cancer or no cancer. And it was scary. And because it was AIS, I didn't get much support from the oncologists because as he felt, there were other graver cases of cancer that he needed to handle, which I didn't know any better. So I thought it was fun. December of 2016, right before Christmas, I went in for my cold knife colonization.

The pre-op was way more serious than I thought it was going to be because I kept thinking good cancer, easy bio. and I would be out, but it was treated like a full surgery. After the surgery, I was told that my margins were clear and that I was good to go and would need no more, no more real oncologist help outside of a follow-up from that appointment. A couple weeks after that, I started getting really heavy cramping and bleeding during times that I was not on my menstrual cycle. And by April, the pain became so severe that I ended up in the emergency room.

in the ER, they ran a scan and they found a really, really small mass on the cervical canal. And I had to go back to the gynecologic oncologist to see what we were going to do next. The oncologist told me basically the best case right now would be to have a hysterectomy. And he actually wanted to wait a couple of years to have the hysterectomy, not because the cancer wasn't serious. But because he wanted to make sure that I was done having children, I have two daughters. They were 10 and 4 at the time. And I felt different about that. He wanted to make sure that I didn't one day wake up and wanted to have a boy, a son.

And I kept telling him that I was done having children. So it was a really, what I felt was an unfair battle I was having with my oncologists because I just wanted to get anything cancerous out of me. so I could, you know, be there for the children I do have. So after about a week, I finally convinced him to just go ahead with the hysterectomy now. And so about two weeks after that ER visit, I was in the operating room again, having a hysterectomy. They took my cervix, my uterus, and my fallopian tubes, and a little bit off the top of the vagina. And recovery was painful.

I went into surgical menopause, which was miserable for that short time that I was dealing with that. And the follow-up appointment, he said everything was great. There was no more sign of any cancer cells or any cancer anywhere. And that I was clear to do annual pap smears for the next five years. So that was the first time that he told me that the cause of the cancer was actually HPV-16 strand. He had not mentioned it, and neither did my gynecologist mention HPV up until that point. And I think that has to do a lot with the stigma behind HPV and cervical cancer. And my last pap smear, which was, I'm going to say, a few months ago,

my gynecologist told me that she once again found HPV strand 16 around my vaginal cuff. So right now it's just being observed. Hopefully it doesn't turn into any kind of cancer again. in the cervical cancer support group that I am on Facebook, I see a lot of women who have to do a lot of radiation, and they have to use dilators so that their vaginas don't seal, and they have to do chemo. And so I understand what my doctors were saying

when they said I was one of the lucky ones, even though I went from thinking I was totally healthy to two surgeries, ER visits, almost losing my job, losing my ability, to ever have another child within seven months, I believe. So I do feel very lucky, even though I know that it was still a hard and traumatic event in my life. But there's, you know, not a day that goes by that I'm not thankful that I'm here. And I'm hoping that this new or old HPV doesn't bring back the cancer in any way. Wow. Thank you so much for sharing your story. We really appreciate it. Thank you. Hi. I'm Erin Wend.

Welsh. And I'm Erin Alman Updike. And this is, this podcast will kill you. Yeah. I'm very excited for today's episode. Me too. I mean, we say this every week and then we say that we say this every week, but... Listen, today we're talking about HPV. Yeah, so we are reasonably excited. Understandably excited. This has been a long time coming. I feel like we've gotten a lot of requests about it. It's a big juicy one in that, like, there's a big biology to it. There's a big history to it. And I think I might be most excited for, like, the current status type stuff. Yeah, because that's a whole big.

I feel like we're just going to end up going on our own Aaron's public health tangents about it all. Probably a bit on like a high horse or like, listen, here's the bottom line. Exactly. So it's going to be great. It's going to be everything. It's going to be everything. But before we get to the meat of the episode, we've got some business to take care of. It's quarantini time.

It is quarantini time. What are we drinking this week? Well, of course, we're drinking the Pabst smear. I feel like I didn't say that great. So I've been not practicing, but every time I say it, I realize, am I enunciating Papsed? Pabst? Like, Papsed? Maybe we should just explain what's in.

it and then it might be easier to hear the pronunciation. It's PBR, Pabst Blue Ribbon, and grapefruit juice, and some simple syrup. Yeah. Because it's like a Papshmear, get it? Papp smear. So this, just like cold as the Rocky Mountain Spotted Fever, was one of the quarantining names that we came up with on the day that we came up with the podcast. It was one of the, like, clinchers.

Like, we have to make this podcast because it's too good of a name to let it go to waste. I still think of, like, even before recording this, I would still think of PAPS smear whenever I drank a PBR. I thought of it every time I got a PAPSmear. Ayo! Well, we will post the full recipe for the quarantini as well as the non-alcoholic placebo-a on our website, this podcast, We'll Kill You.com as well as on all of our social media channels.

Absolutely. Do we have any other business before we dive into this big episode, Aaron? There's usual stuff. There's fantastic, wonderful, beautiful merch. There is a bookshop.org affiliate account. And also there is a Goodreads list where we add the books that we read. And also it's like a nice community list where listeners add books that they think are of the podcast or related to the podcast. Yeah.

Okay. Hey. Well, then let's take a quick break and then dive into this episode. Sounds great. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients so there's no meal planning and no extra grocery trip. There, assemble and bake meals take about five minutes of hands-on prep. Just spread the pre-chopped ingredients on a sheet pan, put it in the oven, and that's it. And if there's truly no time to cook dish by Blue Apron meals are fully prepared. Just heat them in the oven or microwave,

and dinner is ready. And here's the exciting news. Blue Apron no longer requires a subscription. You can order meals when you want them and skip when you don't without adding another recurring charge. Order now at Blue Apron.com. Get 50% off your first two orders plus free shipping with code this podcast 50. Terms and conditions apply. Visit blueapron.com slash terms for more information. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something.

That's why O'Keefe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments. It's been relied on

for decades by people who wash their hands constantly or work in harsh conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters when it feels like my skin is always on the verge of cracking. It keeps them soft and smooth, no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keefs. Just visit o'Keefscom.com slash this podcast and code this podcast at checkout. In 2023, a story gripped the UK, evoking horror and disbelief. The nurse who should have been in charge of caring for tiny babies is now the most prolific child killer in modern British history. Everyone thought they knew how it ended. A verdict, a villain.

a nurse named Lucy Letby. Lucy Letby has been found guilty. But what if we didn't get the whole story? The moment you look at the whole picture, the case collapses. I'm Amanda Knox, and in the new podcast, Doubt the case of Lucy Letby, we follow the evidence and hear from the people that lived in, to ask what really happened when the world decided who Lucy Lettby was. No voicing of any skepticism or doubt.

It'll cause so much harm at every single. level of the British establishment of this is wrong. Listen to doubt the case of Lucy Lettby on the Iheart Radio app, Apple Podcasts, or wherever you get your podcasts. So HPV. HPV stands for human papilloma virus. This is a double-stranded DNA virus, except it's not just a virus, right? Oh, no.

This is an entire family of double-stranded DNA viruses. the papilloma viruses, which include, I don't even know how many viruses, but viruses that infect essentially, I don't know, every animal ever, every mammal that we've ever looked at, birds, turtles, snakes, fish, I think every animal. Fish, that's the one that really got me. Yeah, fish? I had an advisor who studied turtle papilloma viruses. Oh, cool.

Yeah. But today we're talking about the human. papillomalamaviruses, aka HPV. So for HPVs, these are a group of several hundred viruses, which fall into a few large kind of subgroups. They call them alpha, which is the one that we're going to focus on the most today, as well as beta, gamma, delta, there's mu, there's new, there might be a chi, there's a lot of different subgroups of these viruses. And then within each of these different subgroups, there are dozens of different types of HPV, which we're probably all familiar with.

You've probably all heard at some point or another a type of HPV, HPV 16, HPV 6, 11. On top of that, and kind of within these larger subgroups, you can also bin these different HPVs based on the types of cells that they tend to infect. So all HPV viruses infect epithelial cells, which are the cells that make up our outer linings of everything in our body. But we have a lot of different types of epithelial cells on our skin, the linings of our respiratory tract, or our GI tract, or our genital tract. So you can also look at these HPV types as some being more likely to affect the skin, which they sometimes call cutatropic, like cutaneous, like your skin. These are the strains or types that tend to cause warts of all different kinds, right? Everyone knows warts.

But then there are also the mucosotropic types, which preferentially infect cells of our mucosal lining, like the cervix, which is going to be what we talk the most about today. But also the anal canal, our oropharynx, these can also cause warts, generally of the genital tract, or even in our larynx. or pharynx. And so in general, it's these HPV types that we're going to focus on for this episode. All of these tend to be in the alpha HPV category. It gets a little bit more complicated because on top of that, you also have high risk and low risk strains or types. I'm very excited to learn more about this.

Yeah. And that's because that's the biggest story in association with HPV. and that is the risk of cancer. So when we say high risk, these are HPV types that have a high risk of potentially causing cancer, and low risk means they have a very low risk of potentially causing cancer. All right, so let's talk about how these viruses are transmitted.

A lot of times we think of HPV as a purely sexually transmitted disease, and many types are sexually transmitted diseases. and those cause genital warts, and those types also are associated with certain cancers. But there are so many different types of HPV, and really when it comes down to it, they're all transmitted by contact. So sexual contact, but if you have HPV on your hands, then you can transmit it from hand to anything. If you have plantar warts, which are warts on the bottom of your feet, those actually shed so much

HPV that that can end up on the floor and it can live for a really long time and then someone else can walk along that floor and get HPV from the floor. How long is a long time? I think I read months potentially, but I don't know under what conditions. That would be true. Yeah. All right. But basically, if you include all these different types, all these different subgroupings of HPV, it's really everywhere. This is such a ubiquitous virus family. Oh, yeah. And it's quite transmissible. If we look more at sexually transmitted HPV, or if we look just specifically at sexually transmitted HPV, it's estimated that the like per sexual act transmission rate is up to 60%. Wow. Yeah. I mean, the thing is, like by the time you're a couple of years old, you are probably infected with one HPV, right? Right. What kid doesn't have warts at some point in their life?

if everyone has at least a wart. Right. But let's get one thing really clear right off the bat. The vast, vast majority of HPV infections are almost entirely benign. Even if they present with a wart, which not all of them do, in general, over 90%, even of genital HPV infections, will be cleared completely, especially in younger age groups like teenagers and young adults. This process is not super fast. The half-life of the disease,

which it's interesting to talk about a disease having a half-life because we don't usually do that, but that tells you just kind of how long you can end up infected with this and yet still clear it. But the half-life for HPV is thought to be like eight to ten months. So almost all infections will clear in about a year or two. And so is an infection defined as like actively shedding virus or and then like at the end of that infection, the virus is cleared from your body. Your immune system has taken care of it?

Yes. Cleared means that your immune system has taken care of it and you no longer have virus in your cells. And are you shedding that entire time or not? That's a good question. As far as I believe, I believe yes. Okay. I would guess that it, how much virus you shed probably varies throughout that time course. Okay.

But not every infection is cleared. So some types of HPV can cause a more latent infection, where they essentially can stay in our cells for a longer time and over that time period end up causing cancer. HPV is associated with essentially 100% of cervical cancers. Right. And as far as we can tell so far, cervical cancer, it is necessary to have an HPV infection in order to have cervical cancer. It's not the only thing, but it is a necessary part of the cervical cancer process. However, HPV infection is also associated with vaginal cancer, vulvar cancer.

Penile cancer, anal cancer, oropherential cancers, and laryngeal cancers. So that's of the back of the throat and the throat. I think it's interesting because, like, that is not a commonly known thing or it's not something that was commonly, like, spread as part of the public health message. Oh, Erin. I have so many thoughts about that that we'll touch on in the current event section. All right. We'll step down from the platform, like, for the time being. For the time being. Let's get back to our, to our HPV. So the real question, of course, is how on earth can a virus cause cancer? Yeah. Right. And the answer is so fascinating, especially because we have talked about a virus that causes cancer previously, but in a totally different way.

Hepsy? Hepsy, right. This is totally different. Okay, so to understand this, we have to understand HPV, and then we have to understand our epithelial cells a little bit. So let's get into it. We know that, because this is a virus, it has to infect our cells in order to replicate, since viruses use our cellular machinery in order to replicate.

So HPV enters into our tissue via little microabrasions. so you have to have small, tiny little cuts on your skin or mucosal membranes in order for HPV to get in. And then it infects a very specific set of our epithelial cells. It infects the basal layer. That's the bottom layer of our epithelial cells. So think of this as like if you look at a cross section of your skin, you have all the dead skin cells on top that like sluff off when you wipe or wash or whatever. And then you have other layers of cells that are like differentiated.

and they're doing their thing. And then at the bottom, what we have here are these kind of stem cells. These basal cells are the ones that replicate over and over and then produce all of these top layers. They kind of like push themselves up if that makes sense. Okay. Yeah. So that bottom layer is where HPV infects.

Interesting. Mm-hmm. Once they're there, once HPV is in those cells, first, the virus, we'll use our cell machinery to replicate a few times, just so there's like a nice group of them in each cell, like maybe 50 to 100. Okay. And then these viruses have a couple of proteins

that act to help stimulate our cells to replicate. So epithelial cells, like our skin cells, they generally replicate pretty rapidly already compared to a lot of cells in our body. But this HPV infection is like, hey, let's kind of do this even more. Because every time that a cell replicates, it's going to replicate all that viral DNA as well. That's an interesting strategy instead of like, because usually we see viruses invading, replicating in this cell, and then bursting the cell, killing it,

and then infecting another cell and another cell and another cell and doing the same thing. But this is like contained replication. Yes, Erin. You're right. Isn't it? Excit. This is very interesting. So if this happens on our skin or on some of our mucosal surfaces, with most of these HPV types, it might manifest as warts, right? So warts are basically just keratinocytes, our skin cells that kind of grow, they get like extra keratinized. And then as those cells slough off, that's when the virus explodes out and is able to go on

and infect other cells. That is really interesting. Yes. But that doesn't tell us what about cancer. That's not cancer. That's warts. So there's another thing that certain types of this virus have that allowed them to be even sneakier. So the high-risk subtypes have a few extra tricks.

One is that they can actually integrate into our job. genome directly. That's spooky. Yeah. It happens. I love it. So that means that they can do an even better job of disrupting our normal cell functioning because they actually can insert themselves inside our genome, like in between

our DNA. It's like human, human, HPV, HPV, human, right? On top of that, the high-risk subtypes have a couple. of extra proteins, one that's called E6, one that's called E7, maybe also E5, and what these proteins do. So we already know that HPV has these proteins that like tell ourselves, hey, replicate more than you want to. These other proteins on top of that function to suppress a couple of genes that we have in our bodies, which are called P53 and PRB or P retinoblastoma. which in our normal human cells are what are called tumor suppressor genes.

These genes are responsible for doing like a double check. Whenever our cells replicate DNA, these proteins, the proteins that are encoded for by these genes, they're like, hey, let's take a minute real quick. You guys, you made a mistake here. This isn't right. You can't do that. This needs to either be fixed or I'm going to kill you. So it either stops DNA replication or they try and fix it.

And if they can't do that, then they just do apoptosis and they're like, scratch this whole operation. This cell is out of commission. Right. So these tumor suppressor genes are what prevent our cells from replicating out of control and what prevents ourselves from replicating incorrect, faulty DNA sequences. High-risk HPV turns this function off. So not only is HPV convincing ourselves to replicate more rapidly, but as they do so, they replicate incorrect and messed up DNA,

which can lead to eventually, you know how these cells are in the basal layer, the bottom layer of our skin. And normally skin cells replicate up, up, up. this uncontrolled, incorrect division can allow them to invade beyond the basement membrane, which is the layer underneath those basal cells, and invade deeper structures. That's cancer. And is that primarily in the mucosal or only mucosal? Yeah, so this is what happens in the high-risk HPV subtypes, which tend to infect mucosal surfaces.

This is, it's so interesting to me because like, from a virus's point of view, this seems like an excellent strategy. Yeah. So. It's such a good strategy. Like, why don't we see this more, I guess? I think it's very, very complicated. So.

It must be. Yeah. Because this is, it's not just that this virus itself is growing really rapidly. Like this virus has to have a very. intimate relationship with our genome. So it has to have evolved with us for a very long time, I would guess. I actually didn't look into the... You're going to talk a little bit about it, I think, but... I'm thrilled. This is so great. I love when this happens. But yeah, I mean, that's what that would suggest, right? Because it has such an intimate relationship with our genes.

It specifically is turning off these tumor suppressor genes. And like you said, it's a great strategy because now this virus can invade our whole body. Cancer can go anywhere at once once it starts going. How does it disrupt P53? Oh gosh, Aaron. Don't ask me that. Okay. It just does. Yep. That's what I have for the pathophysiology of this disease. It's very fascinating. And it's like, it's very scary. Cervical cancer is the one that we hear the most about. Yeah. Why is that?

Well, first of all, why are those areas so much more susceptible to cancer caused by HPVs? And why cervical cancer most of all? Or is it just that we hear more about it? It's a good question. I think in part we do hear more about it. And we'll talk about kind of why that is. And part of that's because we can screen for it, which is great. It's also, I think, because other cancers that are associated with HPV also have other risk factors or other things that can cause them without necessarily having HPV.

Whereas cervical cancer, it seems that HPV is a necessary precursor. Like, if there's not HPV, the cervix is never going to become cancerous. Okay. If that makes sense. Yes, that is interesting. Yeah. The cervix, by the way, is the bottom part of the uterus. Some people might not know that.

It's very true. Yeah. It's the bottom part of the uterus. It looks. So I guess we'll talk about this so that we can understand why we're able to screen for cervical cancer. And I think, Aaron, you'll talk a little bit more, too, about, like, how someone came up with this. Oh, yeah. Yeah.

So it's the bottom part of the uterus, which is also, if you are looking into the vagina, it's the very top part of what you'd see at the vaginal canal. It looks like a little donut. It's kind of cute with a little hole in the middle. That little hole in the middle goes up, like through that hole would go up into the uterus. And at that zone, right in the middle of that hole, is where the outside body meets, It's the inside body. And there's a transition zone in there where our cells change type.

That transition zone is also very susceptible to HPV infection. Huh. The same is true we think of the transition zone, because there's a similar transition zone in the anal canal where we go from outside of the body to the inside of the body. And that transition zone in the anal canal is also very susceptible to HPV infection. So the transition zone where you, so you have cells turning into different kinds, like that's sort of the border. Yes. And does that have something to do with it?

Just the fact that there are like different instructions. And so like a different type of cell might not receive the same amount of like scrutiny. Yeah. It's possible. So I think from what I have read, we don't fully understand exactly that process. But it is thought that, yes, something about that transition zone and the kind of what's called metaplasia or cell type change that happens there might have something to do with why the cervix. Interesting.

Interesting. But the good news when it comes to cervical cancer, at least, is that it's a really preventable type of cancer. At this day and age, it's a very preventable type of cancer, at least in the same. theory. We can prevent it in a number of different ways. One is by, this is kind of fun because we can talk about the types of prevention, right? Yeah. So in public health, we have a lot of different types of prevention. And one is called secondary prevention. And that's what screening is. So that means we're trying to find precursors of something like cancer or very, very early cancer that we can treat

before it becomes severe disease. So screening, like breast cancer screenings or cervical cancer screenings are secondary prevention. And we can do that. We can scrape off cells at that transition zone from the inside of the cervix and then look at them under a microscope and look for pre-cancerous changes. And that can tell us, hey, you're at risk of having cancer. And then you can go one step further and do a second test where you basically put acetic acid on the cervix and look with another type of special lens to see if there are any changes and then remove those as well before they become cancer or before they become invasive cancer. So that's one type of screening and that's the pap smear combined with what's called colposcopy,

which is the more invasive test. Nowadays, we have another type of screening, which I get very excited about because it's a lot less invasive. It doesn't have to be done as often. And it's as good, if not better. And that is direct HPV testing. So because cervical cancer necessarily has HPV infection, you can test cervical cells really like just a vaginal swab. It doesn't have to be all the way jamming into the cervix, which is a lot more painful. And you can just test for the presence of certain types of high-risk HPV.

And then if you see it, then you go from there in terms of like what you do about it. So that's really exciting because that's secondary prevention that's possible. But even better than secondary prevention is primary prevention. Oh yeah. Primary prevention means preventing somebody from ever getting a disease in the first place. And for cancer, we often can't do that. So for cancer, secondary prevention is often kind of like the mainstay of public health prevention. That's usually all that we can do is try and find it early and do something about it.

But for cervical cancer, we can prevent it because we have a vaccine. It's amazing. We have a cancer-preventing vaccine. I know. It's, we're living in the future. We really are. So there are three different types of HPV vaccines that are currently licensed. One covers four types of HPV.

Two that are high risk, which are 16 and 18. Those cover 70% of all cervical cancer in the world. as well as 6 and 11, which cause about 90% of genital wards, which is awesome. Yeah. There's another one that was licensed a couple years later that only covers 16 and 18, so it doesn't protect against genital warts, but it does protect against 70% of cervical cancers. But recently, in the last couple of years, there's another one that covers nine strains, including 16 and 18, which are the most common causes of cancer,

but also 31, 33, 45, 52, 58, which are all high-risk types that altogether account for 90% of all cervical cancers. That's amazing. And then it also covers genital warts. We'll talk about all of the pitfalls with this vaccine and with screening in general a little bit more later on in this episode. But first, Erin. Ooh.

Where did we? How did we? What is this virus? This cancer virus. Like, what? I know. I know. I'm very excited to talk about it.

Let's take a quick break first. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working. Hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented,

and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments. It's been relied on for decades by people who wash their hands constantly or work in harsh conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters when it feels like my skin is always on the verge of cracking. It keeps them soft and smooth no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keefs. Just visit O'Keefscom slash this podcast and code this podcast at checkout. In 2020, a story gripped the UK, evoking horror and disbelief.

The nurse who should have been in charge of caring for tiny babies is now the most prolific child killer in modern British history. Everyone thought they knew how it ended. A verdict? A villain. A nurse named Lucy Leppie. Lucy Letby has been found guilty. But what if we didn't get the whole story? The moment you look at the whole picture, the case collapses.

I'm Amanda Knox. And in the new podcast, Doubt, the case of Lucy Letby, we follow the evidence and hear from the people that lived in. To ask what really happened when the world decided who Lucy Lettby was. No voicing of any skepticism or doubt. It'll cause so much harm at every single level of the British establishment of this is wrong. Listen to Doubt, the case of Lucy Letby on the Iheart Radio app, Apple Podcasts, or wherever you get your podcasts.

I'm Clayton Eckerd, and in 2022, I was the lead of ABC's The Bachelor. Unfortunately, it didn't go according to plan. He became the first Bachelor to ever have his final rose rejected. The internet turned on him. If I could press a button and rewind it all I would. But what happened to Clayton after the show made even bigger headlines. It began as a one-night stand and ended in a courtroom, with Clayton at the center of a very strange paternity scandal. The media is here. This case has gone viral. The dating contract.

Agree to date me, but I'm also suing you. Please search for it. This is unlike anything I've ever seen before. I'm Stephanie Young. This is Love Trapped. This season, an epic battle of he said she said, and the search for accountability in a sea of lies. Listen to Love Trapped on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. So, first off, to say that papillomavirus, in general, papillomoviruses, have been around since humans became human, would be a bit of an understatement. Kind of an enormous understatement, actually, because papillomavirus are thought to be hundreds of millions of years old. Have they been around since viruses were viruses? I mean, not far off.

The number and diversity of hosts that they infect, like you mentioned, Aaron, fish, birds, mammals, reptiles, etc., and also their diversity within the host species, it just, like, highlights how ancient this group of viruses is. All right, so I found one paper that puts the root of the papillomavirus tree back to 424 million years ago. What? Like this is beyond what anything that we've talked about in terms of like ancientness. Wow. Yeah. And then the first big divergence was around 184 million years ago. And that was during the period when mammal evolution and diversification led to the development of a whole lot of new real estate for these viruses.

Specifically, some of the mammalian skin characteristics like, hairs, sweat glands, sebaceous glands, milk glands, etc. So this is just like open space to occupy. Tons. New territory. Absolutely. And so from that point, there are several other additional diversification events or periods where the papillomavirus diversity kind of like fanned out even further.

But I'm just going to leave it at that because it gets sort of like, and then, and then, and then. Basically, the bottom line is that papillomavirus is are incredibly. old and have evolved with their hosts and that the cancer-causing genes in papillomavirus are not specific to human papillomavirus. And so those genes, it's likely that those genes evolved before humans did. What? So like those genes are likely similar across all of the, like, in different animal viruses. Honestly, that makes sense because P53 is highly conserved.

Exactly, exactly. So it's probably not like convergent evolution, I would guess, anyway, also because of the complexity, but whatever. And because of how old and widespread these viruses are, it probably doesn't surprise you to learn that there are lots and lots of ancient writings about them, or at least about the things that they caused, like warts. genital warts, for instance, have been written about since at least the time of Hippocrates, so like 460 to 370 BCE. And the medical term for them, condolomata acumenata, comes from the ancient Greek and Latin, condoloma meaning knob or round tumor and acumenata from the Latin for sharp points. And a term for planar warts, Miramesia, Mirmechia, comes from. from the Greek word for Ant Hill.

Hmm. I can see that. And in ancient Rome, genital warts were called phicus or thymus, because apparently they looked like an open fig or resembled the leaves of the time plant. Hmm. Yeah. And besides just writings about warts, there was also a tow wart found on the embalmed body of an ancient Egyptian worker from like thousands of years ago. But, you know, like all types of warts, the warts common on fingers. genital warts, planter warts, they all made appearances in ancient Roman and Greek medical texts.

And it was commonly assumed that sexual activity, particularly excessive sexual activity, was the cause of genital warts. The causes of other warts, like those commonly found on fingers, were often chalked up to females addicted to solitary habits, in quotes, aka. Do you know what I mean by that? Oh, I know what you mean by that. Okay. And or also those that, like, regularly were hen testers, so they would stick their finger up the cloaca of a hen to see how close it was to laying an egg. Oh, my God.

I have never thought about a finger going up a cloaca. I don't like the thought of it. I hope that won't become an intrusive thought for you. I think it might, yeah. Well, you know, there are worse things. So anyway, the precise cause of warts was not known, like the fact that they were viral, but they were recognized to be contagious. But for the most part, this early focus on warts wasn't so much on uncovering the cause of warts, but rather how to treat them or get rid of them. Which brings me to one of my favorite things, which is old-timey cures.

Oh, I feel like it's been a very long time since we've discussed old-timey cures. Well, and it's, I feel the same way. And so because of that, I have like quite a big section on this. So I was like, oh, let me, let me find my favorites and I'll put them in here. And I just kept adding more. So, and I'll link to papers that have even more. So this is like specifically old-timey folklore of Europe in terms of how to of warts.

Okay. All words or genital warts? Some of them didn't specify, but for the most part it seemed like skin warts, like finger, toe, whatever. All right. Because, I mean, some of them you will, it's very clear that it's not genital warts. Oh, okay. But, yeah.

Oh, dear. Okay. So these can be grouped into the following categories. One was transference, so like transferring your wart to somebody else or something else. Okay. Number two was animal plet. or mineral remedies. Number three was prayers or incantations.

And number four was miscellaneous at things like crossroads, moon phase, funerals, etc. What? Okay. Yeah, I'll get there. Okay, so a couple examples of transference. You should rub the warts against a man who is the father of an illegitimate child without his knowledge. So that one you'd probably just want to do with hand warts, right? Right. Like, I don't think you could do genital warts. Yeah, no. No.

Not without his knowledge. And then, quote, If a bag containing as many small pebbles as a person has warts be tossed over the left shoulder, it will transfer the warts to whoever is unfortunate enough to pick up the bag. Another one, quote, take one of the large black snails, which are to be found during summer, rub it over the wart and then hang it on the thorn. This must be done nine nights consecutively, at the end of which the wart will completely disappear.

You could also rub your wort with a piece of bacon, cut a slit in the bark of an ash tree, and slip the bacon under the bark, and then repeat the words, Ashen tree, ash and tree, pray by these warts of me. And then you stick a pin into the tree, and then into the wart,

and then back into the tree. And then your warts gone. Of course it is. And there was also, so if those didn't work, there was also the option of having someone buy your wart off you. I guess there was like an open market for that. Or you could treat it with any one of the following. So like fishheads, pigs' blood, lizards blood, menstrual blood, dove's dung, tobacco juice, and fasting spittle. Okay.

I mean, honestly, I could go on and on with more wart remedies, catch a longhorn grasshopper and have it bite off your wart directly. So it was known as like a wart biting grasshopper or something. Of course. It's not a great solution now because the grasshopper species, decticus, varicivorous is endangered. So don't do that. Don't do that. And then finally, spit on your wart and rub it three times in the direction of a passing funeral while saying, my wart goes with you. And when I read that, Aaron, all I could think of was, my wart be with you and also with you. And also with you. So some good ones there. There are many more. That's the title of the episode.

My Warp be with you? Excellent. Anyway, okay, I should move on, though. So from ancient times to around the late 1800s, warts remained a nuisance for many people, hence these innumerable cures described, but little progress had been made in terms of understanding the transmission of warts or their viral cause. But it was around this time that things changed. So the development of germ theory and microscopes allowed more close examination into the contagiousness of these warts as well as to what they looked like at a cellular level, like what was going on. And in 1893, a French dermatologist made the observation that genital warts and common

skin warts might be the same thing or caused kind of by the same thing. And other doctors successfully gave themselves warts. So, like, they were like, oh, I'll try this out. I'll try to put some wart juice on me and, you know. Like from, like, they gave themselves skin warts from someone's genitals to test it? Well, so that was mostly skin to skin, but then in 1906, there was a major breakthrough when an Italian doctor made an extract of genital warts and then passed it through a filter that would leave out any bacteria or fungi, and then he injected this wart juice into his skin where warts later developed. That is some commitment right there. It is. And I mean, this this led to two important pieces of information.

One was that warts are probably caused by a filterable transmissible agent, aka a virus. And it also showed that genital warts and skin warts were caused or could be caused by the same virus. The virus itself that caused the warts or any human papillomavirus wouldn't be discovered until 1950. Wow. But yeah. But in the meantime, there were a couple of other important developments. So I'm going to shift gears for a little bit and talk about cervical cancer. In the early days of cancer research, it probably seemed like with every new thing you learned,

you probably had 10 times the amount of questions you started out with. Because there didn't seem to be a single unifying cause of cancer or even predictability within the same type of cancer. New cancers were being discovered all the time. like it seems like an utterly chaotic field in that sense. Oh, man, I still feel like that. Yeah, absolutely. And then in 1910, a key piece of research seemed like scientists were getting closer to at least one solid answer.

Because that year, a pathologist named Peyton Rouse described how he was able to induce malignant tumors in healthy chickens by injecting them with a filtrate from malignant sarcomas in sick chickens. In other words, Rouse discovered the first cancer-causing virus in 1910. 1910? 1910. Like, not only was this super exciting, but it was also a very important development in our understanding the nature of viruses and cancer. And Rouse was awarded a Nobel Prize in 1966 for the finding,

which I think is like the longest actually delay between work and award like in Nobel Prize history. Wow. After the rouse sarcoma virus was discovered, many other researchers began looking into possible infectious causes of cancers. And one of these researchers was Richard Schope, whose name may sound familiar because he was one of the people who discovered the influenza A virus and linked it to the 1918 influenza. That was literally. three and a half years ago. I do not remember his name. Well, but his name also might sound familiar because his son, Robert Schope, was a famous virologist who worked on arboviruses mostly and discovered more novel viruses than anyone else previously. Wow. Like unbelievable amount of

virus like research. He was like a walking encyclopedia apparently. Wow. Anyway, Wikipedia rabbit hole. Speaking of rabbits. In the 1930s, Shope, who had collaborated with Rouse, was out hunting one day in Iowa when he noticed what looked like a wild cottontail rabbit with horns. These rabbits, these horned rabbits, were a strange thing to see, but they weren't unknown. Like, there was already sort of this, first of all, like everyone who was a hunter out there was like, oh, yeah, we see this all the time. Yeah, there's a jackaloupe. Secondly, there's the jackaloupe. It's actually thought that these horned rabbits might have given rise to the jackaloupe myth.

Yes. That's awesome. That's awesome. So Shope trapped some of these rabbits so he could get a closer look at their horns and discovered that the horns were actually cancerous growths caused by a rabbit papillomavirus. What? Yeah. So the jackalope is just a rabbit infected with a cancer-causing papillam virus.

Poor jackalopes. Oh, gosh. And he was able to, in the lab, induce these cancers in other rabbits through, like, passing on the virus. Wow. And I also realize I haven't done the etymology for papilloma, which comes from a combo of Latin and Greek words that together mean a tumor resembling a nipple. There you go. Just going to leave that there. And then the final big piece of like news or developments happened in 1964, which is when the discovery of the Epstein-Barr virus and the fact that it could cause Burkitt's lymphoma showed that cancer-causing viruses didn't exist solely in animals but could also cause cancer in humans. Okay. So at this point, all of the pieces were in place to link HPV to cervical cancer. But that didn't happen right away. And in order to tell that part of the story, I want to dive a bit into the history of cervical

cancer to give a bit more context. Cervical cancer doesn't leave any marks on the skeleton, so we have to rely on early descriptions of what we might think might be cervical cancer to understand sort of the perception of the disease as well as to guess as how long it's been around. although, like, given how ancient these viruses are and how, like, everyone is infected with them, it's safe to assume that cervical cancer has been in humans from day one. Although it was one of the papers I read noted that the rate of cervical cancer probably increased over time, not due to, like, human travel or increase in population density, which might have had a role to play,

but due to the nature of cancer in general as a disease of longevity. Like when life expectancy was lower, people were less, were more likely to die of something else before getting cervical cancer. Yeah. It's a long time period from infection to cancer for cervical cancer. So that makes sense. And there are some ancient writings, ancient Egyptian papyri, and some Hindu manuscripts from like the 4th century BCE. And then also in ancient Rome, there was a device uncovered that looks like a very early speculum. which is pretty interesting to think about, like the first century. I bet it's painful. Oh, yeah.

And it's going to get a lot more painful, I think. Yeah. Because early treatment for ulceration or malignant growth of the uterus or cervix was usually something along the lines of cauterization or partial removal. But honestly, those things usually ended up leading to just a quicker death. By the 1600s, 1700s or so, people had started to make the distinction between malignant and benign in these uterine or cervix tumors. But the distinction was pretty much useless because it generally involved the doctor just going, okay, this patient is wasting away and dying, so this must be malignant.

Or this tumor doesn't seem to be changing at all. So the patient's probably fine. Great. Essentially, yeah. Essentially doctors were just sitting around waiting for their parents. patient to die or not. As you might have guessed, many doctors were not especially content with this type of hands-off medicine. And so they began to explore treatments such as Belladonna, hemlock, strychnine, lead, mercury, etc. Basically like any very toxic intense compounds. All kinds of

things that can kill you. And of course, nothing worked. And the birth of the field of gynecology didn't exactly help things either right away. Gynecology began to be recognized as a separate distinct medical field around the 1700s, 1800s, but not to gather knowledge that would improve the health of women everywhere, but rather to detect sexually transmitted diseases and sex workers. Basically, a big part of the push for gynecology was to protect the main. clients of sex workers. Like you were given a clean bill of health and allowed to work or you were held in the hospital until you got better against your will. In this burgeoning field of

gynecology, tools to help assess vaginal or cervical health were needed. And so they were developed. For instance, the duck bill speculum, which is very close, if not the exact thing that we use today. That was developed by James Marion Sims, who was the so-called, called father of modern gynecology, and also one of the most unethical people I have read about while working on the podcast. Not surprised about that. Oh, no. He operated almost exclusively on enslaved black women and never with anesthesia and conducted

all sorts of medicalized torture as well as perpetuated a lot of misinformation. Please read the book Medical Bondage by Deidre Cooper Owens for more info about him. It's so good. Okay, anyway, back to cervical cancer. So what these new and improved speculums did was allow doctors to visualize these different lesions and record their observations so that ultimately the link between cervical lesions or cauliflower growths and later developing advanced cancer of the womb was made. And this visibility or observability of two of the most common cancers to affect women,

so like breast cancer and cervical cancer, led to cancers over. overall being seen as if, quote, female ailment, usually attributed to some part of the woman's reproductive tract. So like, oh, you know, like hysteria, right? Like, it must be from an overactive uterus, like as if anyone knew what that meant. Yeah. A wandering, a wandering uterus. A wandering uterus. So, and then second book recommendation here, illness is a metaphor by Susan Sontag. Okay. So once doctors had made the link between these lesions and cancer, they started to try to treat these ulcers to prevent their spread. Again, cauterization or treatment with corrosive chemicals, or simply removal of the affected areas.

So like full on trying to remove a cervix or uterus, these were pretty much like the options that they chose. And in these days, these more drastic options were nearly almost always fatal. And in the days before anesthesia, unbelievably excruciating. Even after surgical practices and diagnostic tools improved, focus turned towards ways to detect cancers early and prevent them from spreading. Enter the pap smear. The pap smear was developed by. none other than Dr. George Papanikolao in the 1920s. The 1920s?

Yeah. I didn't realize it was that long ago. Yeah. So he had started work on mice to develop a lab test to show how changing levels of estrogen could be detected in changes in the vaginal lining. And he was like, well, I really want to translate this research into humans. I could use it to stimulate menstruation or treat infertility. But then he was like, I actually have no idea what a normal vaginal smear looks like.

Like, what's the baseline? And so once he started looking for that baseline, he began observing that some of the smears had irregular looking cells. And subsequent gynecological examination revealed that they had early cancer of the cervix. And his article that described this finding didn't really gain a lot of traction. and many doctors remain skeptical for a number of years, but over time, this use for vaginal smears grew, and they were then named the Papinicalau or Papp smear in his honor. Dr. George Papp.

Papp. The Papp smear, especially the simplified version of the test, which was developed by Dr. Anna Marion Hilliard in the 50s, I think, did a lot to advance knowledge in terms of what proportion of lesions were likely to remain localized and which were likely to advance to invasive malignancies. And the 1960s and 70s continued with this trend of early detection and lesion removal with fewer and fewer hysterectomies performed, instead being replaced by less invasive surgical procedures. And so this was a great improvement from the early days of cervical cancer.

Early detection methods had been developed and physicians realized that pre-cancerous lesions were pretty fragile, meaning that their removal often meant that the cancer itself was gone. But issues remained. These cervical biopsies, which were described as minor surgical procedures, not only still had and have risks associated with them, but they could also be very painful and associated with uncomfortable side effects. And a positive diagnosis itself could be quite terrifying, since it's, you know, you could be quite terrifying, since it usually meant additional diagnostic tests, which can be distressing, especially because

there often was an adequate communication, and that problem lingers today, about what exactly the tests are for or what the finding is. The consensus, of course, and I know you'll talk more about this, is that regular screening helps detect and effectively treat cervical cancers, but that in many places clear guidelines didn't exist or were being developed at a slow pace for how frequently someone should be tested or the age group that should be tested. I could get literally so excited talking about guidelines. Oh, yes. And I think that often, like, one of the biggest problems is just, like, once again,

we always come back to this communication, right? So, like, not just in public health campaigns, which, like, those were pushed really hard in the 60s and 70s, but also between physician and patient, right? Like open communication, clear communication, ask as many questions as you want. I will be as, you know, direct and informative as possible, whatever. So anyway. But the bottom line is that for the most part, effective treatment is no substitute for complete prevention. Yeah.

And the only way to do that was to understand what caused these cancers. This was not a new question. Even before cancer, like the Big C cancer, was defined medically or cellularly, people had wondered about the causes of various cancers, including cervical cancer. And there was quite a long list in the case of cervical cancer of suspected causes. Masturbation, excessive sexual activity, sexual abstinence, sterility, syphilis and other STIs, Great Sadness, Dangerous of... Great Sadness! Great sadness. dangers of urban life, fright, childbirth, abortion, and menopause.

Literally anything. Anything. Yeah. Anything that happens near the cervix. Yep. Then the field of medical or health statistics finally shed some light on the issue in the mid-1800s when Italian surgeon Domenico Rigoni Stern published his findings that nuns had a much lower rate of uterine cancer. and a higher rate of breast cancer than married women.

And this did not distinguish between like true uterine versus cervical. Right, versus true urine. This research not only hinted at a potential sexual link to cervical cancer, but it also suggested that different cancers might have different causes, which is, puts like a pretty big... That's a huge. Yeah. That's in the 1800s? Yeah.

Wow. Yeah. Other research from around the same time supported the sexual link. In 120 cases of uterine cancer, 5.83% were from single women, 86.6 were married, and 7.5 were widows. Later, when cervical cancer was distinguished from cancer of the uterine body, the link between sex and cervical cancer remained. And additional evidence, like how cervical cancer was lower in groups that practiced male circumcision, and how sexually active but unmarried women experienced similar rates of cervical cancer as married women, these things further supported this link. It seemed so clear that cervical cancer was tied to

sexual activity that by the 1970s, there were articles in scientific journals asking if cervical cancer was a sexually transmitted infection. I mean, and it certainly seemed to be, but which one? Which one? Was it syphilis? Tricamonis? Gunneria? Or how about the great boogeyman of the sexual revolution? Herpes Simplex 2. Must have been Herp. Must have been Herp.

And this last one, HSV2, I keep like I was like HPV, HSV. This last one, Herpes Symplex virus 2, this emerged as the favorite, partially because it did have some support from epidemiological studies. But at least one researcher wasn't so sure. Dr. Harold Zerhausen, who is a German virologist, could not find herpes simplex virus to reliably in the many cervical cancer biopsies he screened. And so he came to the conclusion that it wasn't the cause. And he presented his findings at the 1972 get a load of this name, International Conference on Herpes Virus and cervical cancer.

So like it was very pretty much accepted in that like there was a whole conference about it. So when he presented his findings, he was met with, quote, stony silence, which he later felt to be, quote, the low point of his career, which is really depressing. Poor guy. But he wasn't discouraged and he continued his work on HPV, which he thought was a much better candidate for cervical cancer than herpes. So that was the low point because things went up from there. Things went way up. He published his hypothesis in 1976 and that was a year before his last. group discovered that, yes, there were actually multiple types of HPV. And the final breakthrough

came in 1982 when his research fellow, Mattaya Durst, isolated a new HPV type, HPV-16, from a cervical cancer biopsy. He came up with the naming system, by the way, or like the numbering system. Oh, okay. HPV-18, another cancer-causing type, was found shortly after, and nearly all of the lab specimens of cervical cancer biopsies contained one of these viruses. And to Zerhausen, the link was clear, as was the path forward. In 1984, he approached pharmaceutical companies to start working on a vaccine, but they all turned him down, saying, yeah, that's not going to be profitable. There are more urgent problems to solve.

I know. And the scientific community was like almost as dismissive of his findings for the most part. Like it wasn't really until the mid-90s and after extensive epidemiological work that there was wide consensus on HPV's role in cervical cancer. And the landmark study that erased all doubt was published in 1995 and involved over a thousand cervical tumors from 22 countries. And it showed that 99.7% of the tumors were HPV positive. So then 11 years after this study in 2006, the HPV vaccine Gardasil, the first HPV vaccine, was approved by the FDA to considerable controversy.

Oh, yeah. Which I think you'll go into. And since then, many other countries have approved its use and incorporated it into recommended it into recommended vaccination programs to varying degrees of effectiveness. and also with some very interesting messaging. I also want to note real quick that Zerhausen was awarded a Nobel Prize, I believe, in 2008, for making this link. I'm sorry. I just want to go back to the fact that this link wasn't cemented in scientific consensus until the mid-90s. That was sort of like the final.

I think that there had been steady growth of acceptance. of this. Yeah. But, um, oh my. Yeah. It's um, it's an interesting timeline that it's fascinating that timeline, Aaron. So, Aaron. Oh. I'm hoping you're about to tell me more about some of these vaccine controversies. In particular, how the vaccine was targeted to certain groups or certain people and how much of an impact we can see now 15 years after it was first introduced. I can't wait. We'll get into it right after this break. I want to get into all of that juicy vaccine info and cervical cancer statistics and everything. And also just like a lot of Aaron and Aaron's hot takes. How about that? But first, let's bring it all the way back to HPV for a

minute, because I really want to stress just how prevalent this virus is. And this is specifically for genital HPV. So we're not even going to account for the fact that every child probably has a wart and a lot of adults do too at some point on their skin. When we're talking about genital HPV, point prevalence, so overall, if you just, at any given time took a sample of random adults, anywhere from 3 to 45% of them would be positive for HPV, even without any symptoms. That's, I mean, that's a very high percentage. And that's just point prevalence.

If you look at lifetime risk, which means because most people who get this infection will clear it. So they might have had it, but when you sample them, they come up negative. So if you look at lifetime risk, we're talking 80% of people. are likely to be infected with HPV at some point in their lives. It's almost an inevitability. It's almost an inevitability. But that's just HPV. Let's now focus on cervical cancer because we have the most data for cervical cancer.

So worldwide today, well, 2018 data, cervical cancer causes an estimated 570,000 new cases every year. with 570,000? 570,000 new cases and over 311,000 deaths due to cervical cancer. Every year. Every year. HPV worldwide is the fourth leading cause of cancer in people with a cervix. The fourth leading cause of cancer in people with a cervix worldwide.

It's so interesting to me the lack of visibility. between something like breast cancer, lung cancer, and then cervical cancer. Well, here's part of it. The vast majority of these new cases and deaths that are due to cervical cancer are in low and middle income countries, where access to screenings and vaccines is very limited if it's even existent at all. Mm-hmm. If we look briefly at data in the U.S., there is an estimated 36,000 new cases of HPV-associated cancers every year. That's all HPV-associated cancers.

Okay. So in the U.S., that includes about 14,000 cases of oropharyngeal or throat cancer, 11,000 cases of cervical cancer, 6,000 cases of anal cancer. and over 3,000 cases of vaginal or vulva cancer. And 1,000 cases of penile cancer. Dang. That's a lot of humans. That's a lot of humans.

Worldwide. And I do kind of want to focus on this for a second because it's so underrepresented. Like talk about cervical cancer being underrepresented. 85% of anal cancers are associated with HPV. 85%. 46% of penile cancers, HPV. Anywhere from 33 to 72% of oropharyngeal HPV.

It's a lot of cancers. Yeah. And while we have screening programs in a lot of places that can detect cervical cancer, which is incredible because it's very effective. The PAP smear is a screening tool that can detect cervical cancer. detect pre-cancerous changes that can then be treated so that it never becomes cancer. If we had something equivalent to a pap smear for like other kinds of cancers, I mean, it would be incredible.

Absolutely incredible. It's hard to wrap your brain around just how amazing. It is to be able to be like there is cancer developing or pre-cancer developing. We can do something about it. The other thing too is that the way that you can then treat those. pre-cancerous changes that you might detect on a pap smear is also not nearly as invasive as the way that you would need to treat pre-cancerous changes if you could even detect those other places. So not only are we able to detect pre-cancer before it becomes cancer, but we can then also

treat it before it becomes cancer. It's really similar to the way that we can do colon cancer screenings. That's really the only other one that we can do in the same way, where if we see a polyp, we can remove it, and we treated your cancer before it became cancer. Gotcha. Yeah. And that's incredible. But it isn't perfect. Papsmears are an invasive test. They're uncomfortable.

A lot of people might not be comfortable even getting them, even in places where they are easily accessible. They're also both operator and reader dependent. And so it requires a lot of infrastructure. that in low and middle income countries just might not exist at all. And in some cases, because they are so dependent on the reader and the operator, they can be overread and then potentially lead to unnecessary procedures that do have risks associated with them.

So they are not a perfect thing. But on top of that, they are specific to cervical cancer. And HPV causes a lot more than just cervical cancer. So the fact that we have a vaccine is beyond incredible. Yeah. Because this is a vaccine that can prevent all of these types of cancer, not 100% of all of these types of cancer, but 100% of cervical cancers and a lot of the proportion of all of these other cancers.

So the question is, why do we even still have cervical cancer 15 years out from this vaccine? Well, a lot of different answers there. It's a lot of different answers. Like you said, Aaron, a lot of it in certain countries like the U.S. has to do with how this vaccine was marketed at the beginning. In most places where it was rolled out, it was only recommended for people with a cervix, except it was marketed as give this STI prevention vaccine to your young girls. Mm-hmm.

Mm-hmm. And so that was interpreted by a lot of people as a vaccine to, like, promote sexual promiscuity, which we all know is not allowed in our culture. And also, like, that's not what this vaccine does. Not in the slightest, but that is absolutely how it was perceived. Yeah. So the marketing failures were really immense. But on top of that, this was a very expensive vaccine, especially when it first came out.

Holy cow, yeah. It was $120 a dose, which compared to most childhood vaccines is immense. You can imagine that in low and middle income countries, that is absolutely an unattainable cost. even for most people in the U.S., $120 a dose for a vaccine that needs two to three doses, that's a lot of money. And is it $120 a dose in other countries as well, or is it just the U.S. has artificially inflated the price because that's just what the U.S. does? So I couldn't get a great answer to that.

It varies a lot. But today, because of a lot of different institutes that help subsidize the funding, it can be available in a lot of countries as low as, in theory, 20 cents or 450 a dose. Since 2008, which is just two years after it was introduced, Paho, which is the Pan American Health Organization, has been subsidizing HPV vaccines at $8.50 per dose. So Latin America and the Caribbean actually have the highest proportion of countries that have national programs.

That's cool. If you look at all the different regions. But overall, not a very impressive percentage of countries have instituted national HPV vaccine campaigns. As of late 2017, only about 40% of countries had instituted national HPV vaccine programs. And you can imagine that the percentage varies greatly based on income. So 77% of high-income countries have vaccination programs, but only 7% of low-income countries have vaccination programs. So this vaccine is not being evenly distributed across the country.

globe, which is why we still have cervical cancer deaths happening every day across the globe. It is so frustrating. It really is. The World Health Organization has a lot of different goals to try and address this. Their current goals are to vaccinate 90% of people with a cervix by age 15 and screen 70% of people with a cervix at least twice between the ages of 35 and 45. because again, screening is still really important. But we are nowhere, nowhere near those goals.

And I understand that you have to have reasonable goals, or at least like benchmarks, but like why is it still just people with the cervix? Why is it not everyone when everyone can become infected? Everyone can develop some kind of cancer and everyone can transmit it to somebody else. Erin saying it. That's like the biggest. I, okay, I get so intense when I think about that. And I honestly, because in the U.S. now, finally, the recommendation is everyone, all adolescents

should be vaccinated starting at age 11, 12. It can be as early as 9. I have issue, big issue, with the fact that the U.S. still doesn't make this a mandatory vaccine for school entry. it's absolutely absurd in my Aaron's personal opinion because D-TAP is required, meningitis is required, hepatitis B is required, and that's not roaming around schools. So like, come on. But anyways, globally, you're right.

The recommendation still isn't for everyone to get this vaccine, even though we know that not only can people with a cervix get HPV from people without a cervix. So if you're not vaccinating everyone, then you just have a bunch of people that are, harboring HPV to then be spread to everyone else. But also, yeah, then we're not preventing penile cancer or anal cancer in people without a cervix or opharyngeal cancer. Like, this is a lot bigger than just cervical cancer. This is a vaccine that can prevent a lot of different types of cancer. Everyone deserves access to it. They do. It's endlessly frustrating. It's endlessly frustrating. My big question is part of the controversy around the HPV vaccine when it first was released

was that, well, we don't know whether it's going to prevent cancer. Oh, yeah, Erin. Right. So now it's been 15 years. We should have seen the effects, right? In the generation, the first cohort that was vaccinated. Yes. Well, first of all, I have a question about the average age of onset for cervical cancer.

Oh, it's 59 is the average age of death due to cervical cancer. cancer. Okay. But it could happen earlier. Absolutely. And it's one of the most common causes of cancer in people with the cervix under age 40. So it can definitely happen in younger people as well. Because this is a sexually transmitted infection that has kind of highest incidents at younger ages, but usually takes 10 to 20 years to then cause cancer. Okay. And then younger people are also more likely to clear the infection. So it's kind of, yeah. Another question about the vaccine's durability. Uh-huh. How long are you protected? Well, that's a very good question. We know for sure at least eight years, it's likely even longer than that. Okay. Yeah. It's likely pretty long-term.

And there's some cross-protection as well. So even though even the sort of broadest vaccine that we have covers nine subtypes, there's thought to be at least some cross-protection to protect you against further types as well. Gotcha. If that makes sense. But you have full protection against either two, four, or nine subtypes depending on which vaccine you get. But you asked Aaron, do we have any data to say this actually prevents cervical cancer? Because you're right. When this vaccine first came out, everyone was like, well, it protects against HPV infection and maybe like pre-cancer, but we can't say for sure that it protects the cancer. Like, give me strength. I know, I know. It does. The answer that we have now is, without a doubt, it absolutely does. If you'd like some hard data on it,

there's a beautiful study out of Sweden where they implemented a school-based vaccination program and studied over a million people with a cervix, about half of whom received the vaccine, and over the time period studied, only 19 people who had received at least one dose of the vaccine were diagnosed with cervical cancer, while over 500 who hadn't were diagnosed with cervical cancer. That's pretty clear. What's even more clear is that the protective effects were far stronger for people who were vaccinated before age 17. So the earlier that people get the vaccine, the better it works.

only because it seems to work better in younger people, but you have to get this vaccine before you are exposed to HPV. HPV is a sexually transmitted disease, which means you need to get the vaccine before you ever have sexual activity for it to be the most effective. And so you mean any HPV or you mean just the sexually transmitted HPVs? Sexually transmitted HPVs. Yeah. Okay. Yeah.

So that's why the recommended age is 11 to 12 or even as young as 9. Because the idea is to give it to people who have not yet engaged in sexual activity, like well before so that you're really preventing this. Now, that doesn't mean that you can't get it if you have already had sexual activity or if you're over age 12. It's recommended as like a catch-up up to age 26. And now it's approved all the way up to age 40. Huh. So that's HPV, guys. And cervical cancer.

It's so interesting. Mm-hmm. Mm-hmm. This is a big one. Oh my gosh. It's way bigger than I thought. I feel like I talked for seven years. There's a lot to talk about.

I mean, I'm sure that I missed a lot of things also. So why don't we talk about our stuff? sources so that people can do a lot more reading and learn all the things that we probably forgot. Sounds great. So I will shout out just a couple of things. One is a book called A Woman's Disease, The History of Serbical Cancer by Ilana Lawi. Then also a paper by Onon-At-all history of human papillamoviruses, warts and cancer by Van Dorslayer, 2013, evolution of the papillum Veridae. And finally, a great paper by Burns, 1992, Warts and All, the history and folklore of warts. I love it. I have a lot of different papers, ranging from everything from

a lot more detail on the path of physiology and natural history of HPV infection and the specific mechanisms on how it causes cancer all the way up to the global distribution and the effects of the vaccine and all of that kind of stuff. You can find a list of our sources from this episode and every single one of our episodes on our website. This podcast will kill you.com under the episodes tab. Thank you to Bloodmobile for providing the music for this episode and all of our episodes. Thank you to Exactly Right Network of whom we are very proud to be a member. And thank you to you, listeners, for listening and for suggesting this episode so many times. We're so excited to finally give it to you and hopefully you like it.

I learned a lot about the history of HPV and cervical cancer, which is exciting. Yeah, I learned a lot about the biology and the current events. My gosh. Wow. How about that? Well, until next time. wash your hands. You filthy animals.

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