[Music] And these viruses are very, very common, right? So, at the age of 50, about 80% of people have been exposed to them. So it's not something that some people have, and if you're lucky and never get it, the chances are very, very high that during your lifetime, you get infected with HPV. [Music] Biological with Florian Kramer. [Music] Hello and welcome to this week's episode of Virological. This was recorded on March 2nd of 2026 in Oulu in Finland. And today we're going to talk about the human papilloma virus. Why is this called papilloma virus? Because these viruses can cause wards, and wards are also called papillomas, and that's why they're named like that. Papilloma viruses are very diverse, they're a large group of viruses, that infect many different species. So, not just humans, but many other species. And in terms of human papilloma viruses, they're also very diverse. We have more than 200 types in humans. And not all of them are widespread, not all of them are problematic, but some of them cause wards, and some of them cause cancer. So people shouldn't know about them. Human papilloma viruses are DNA viruses. They have a double-stranded circle at DNA genome. And in this case, you have to double-stranded DNA genome on the inside of the particle. Then this is covered with his stones. And then the virus doesn't have a lipid envelope in this case. So it's just a capsid shell that we have on the outside. And the interesting part is that this capsid shell is very regular. It's made of two proteins, an L2 protein, that is the minor component. And then we have an L1 protein. And so this L1 protein comes together spontaneously to form pentamers. So, five of these proteins come together to form one bigger structure. And then 72 of these pentamers come together. It's specifically 72. And they basically assemble into a virus particle. That's happening because when the protein basically assembles, first into these pentamers, and then into particles that have these 72 units, the state of the proteins achieve thermodynamic minimum. And that's by this self-assemble. That's this process. The particle itself is about 60 nanometers in diameter. And these particles are relatively stable in terms of pH and temperature. And more stable than many other viruses. And that of course helps them spread. Papilloma viruses were first discovered by Richard Chop, who was a US biologist. And he made the association between papilloma viruses and words that developed in rabbits, in infected rabbits, in 1932. As I already mentioned, there are about 200 types of human papilloma viruses. And these viruses have been in humans for a long time. So it might be a year, but people like Spantepu apple, for example, developed techniques of how to sequence ancient DNA from old bones, for example. And they have done this with homonion nanodilenses, with nanodiles, for example. Right? And so the genome of nanodiles has been basically elucidated and assembled from DNA fragments from their bones. But in these data sets, these DNA sequences, people also found genomes of human papilloma viruses. I mean, that's DNA that also survived and that could also be sequenced. And that means that the nanodiles already had human papilloma viruses. And it's very likely that Stone Age humans also had already human papilloma virus infections. So it's not really clear how long the virus is in humans already and how it got there. But probably for a very long time, it's very likely that the virus co-evolved with human. That these viruses co-evolved with humans. What's interesting about these viruses is that they don't cause symptoms that we typically associate with viral infections, where you might get fever or other symptoms that that children infected. That's not the case with human papilloma viruses. These viruses are mostly transmitted by sexual contact. Most often end up on the mucosal surfaces of the reproductive tract, but also in other areas, other mucosal surfaces. But some of them also, when they end up on the skin and the regular skin, they can infect the skin. So once we come in contact with them, they bind to receptors on cells. As I said, mostly on these mucosal surfaces, those are often special cells that infect epitelial cells or basal cells. And they start to infect these cells. But these viruses have a problem. They don't have their own polymerase, so they don't have an enzyme that copies their genome. And so in order to grow, they need the DNA polymerase of the host cell to have our cells. They need active DNA polymerase. But most of our cells are not growing. They are terminally differentiated. They're just cells in the body, but they don't grow much. And so they don't have a lot of this DNA polymerase activity. And that's a problem for the virus, because the virus goes into a cell, and then the genome gets not copied, right? The virus can grow. And unfortunately, the virus has overcome that, and it just expresses a number of proteins. The most prominent ones are the E6 and E7 proteins. And basically, the virus forces the cells to start multiplying and to proliferate. And when that happens, the DNA activity is high, and that means also the genome of the virus gets copied, gets multiplied, and that allows the virus to grow. Now here's the issue. These cells are not supposed to grow. And when they start growing, unregulated, that can lead to the formation of wards, but it can also lead to the formation of cancer. And so that's why these viruses are really problematic. And so we know that certain types of human papilloma viruses cause certain issues. We know that HPV611, but also 1340 and 43, cause genital wards. Types 1, 2, 4, 27, or 57, for example, cause wards on skin, so on regular skin. And of course nobody likes wards, especially nobody likes genital wards. But these viruses are not not a problem in terms of causing severe disease or death. But there's other types, and specifically type 16, 18, but also 31, 33, 45, and so on and so forth, are worse because they cause cancer. And we know that type 16 is responsible for about 50% of all cervical cancers. And type 18 is responsible for approximately 20% of all cervical cancers. So that's a huge issue, right? And so this connection between cervical cancer and HPV and defected HPV causes cervical cancer was discovered by Harald tohausen in the 1980s, and he got the Nobel Prize in 2008 for that discovery. And so the important thing to realize is that these viruses can be transmitted by not just women, but men and women. They can infect men and women. They can cause cervical cancer in women, but they can also cause anal cancer and had a head and neck cancer in both sexes. And in men they can cause b-neil cancer. So these viruses are really problematic. They're not just a problem for women, they're also a problem for men. And circulation of these viruses typically begins when people become sexually active. So the highest prevalence of HPV in the population is in the segment between 14 and 30, but you can also find them in older age groups, but they have lower prevalence. What often happens is that one gets infected and then the immune system actually hears the infection relatively quickly before the virus can do a lot of damage. But that's not always the case. In many cases, infection can last for months, sometimes for years, and can become basically persistent infection. And there's this saying that HPV infections last usually longer than the relationships that cause them. But the problem is when the infection persists and the virus starts to infect many cells, then the risk increases that some of these cells become cancerous. And these viruses are very, very common, right? So at the age of 50, about 80% of people have been exposed to them. So it's not something that some people have, and if you're lucky you never get it, the chances are very, very high that during your lifetime you get infected with HPV. And
And as I said, there is a high risk for cervical cancer in women, but also risk of HPV-related head and neck cancer that has, for example, been rising in the United States over the last decade. The good thing is that something can be done about this. Vaccines have been developed and licensed in the 2000s. These vaccines are based on virus-like particles. They're made with a trick. So I was talking earlier about this L1 protein, right? That forms most of the virus capsid. And they're told about the self-assembly and the termed anemical minimum, right? And so it turns out when you express this L1, we're commonly different cell types, different expression systems, and you purify it, it also self-assembles into particles. They look just like HPV, but they're empty inside. They don't have a genome, and we call these virus-like particles. And so the immune system recognizes them and makes neutralizing antibodies when it sees them, but they can't do anything because they have no genome. They can't do any harm. And that's the beauty of these things. One of these vaccines called server-ix contains HPV types 16 and 18. So remember those are the high risk ones for cancer. And this vaccine is etuated with ASO4. That's just an etuvent that increases the immune response to it. This is a vaccine that has to do high risk types. And this is made in insect cells. It sounds strange, but it's basically the same way how the Novavx COVID-19 vaccine is made. So insect cells are common production systems for vaccines. Another vaccine that was developed is called Gardasil. And that's actually made in PAKAS used. So psychoramizes are easier. So you can also make recombinant proteins, recombinant antigens in PAKAS used. And then purify that and use that as a vaccine. Gardasil is quadrivalent. That means it has four components. It has type 16 and type 18, so the high risk cancer ones. But it also has type 6 and type 11. And those are the ones that are causing most genital wards. And then there was a new development that's called Gardasil 9. So that's 9 valent. There's 9 components in there. Here we have type 16 and 18, so the most dangerous ones. But also rare types that also cause cancer, including type 31, type 33, type 45, type 52 and type 58. And in addition, we have type 6 and 11, which are the ones that cause genital wards. And so this vaccine gives a very broad coverage and has an efficacy of over 90% for prevention of cervical cancer. In total, there are now six vaccines that are W-Choke qualified. And they're basically potentially global, they're available. Although there are some countries that haven't implemented them, other countries that have active vaccination campaigns with them. And they'll get to that in a minute. Of course, it's best to vaccinate before sexual contact start. Many countries basically recommend vaccination between age 9 and age 14. And then basically infections are prevented. It's also important to mention that girls and boys should be vaccinated because while the risk for cancer is higher than girls, boys spread the virus too. And if they're vaccinated, they don't spread it. And that reduces the risk in general. So typically, it's best if you give this vaccine to teenagers or pre-teenagers. But it has also been shown that it's very helpful if people that are in that 20s are surdiscared vaccinated. It prevents fewer infections too because many people at that point already had been infected with HPV, but it still has an effect and it's still very advantageous to get the vaccine at that point. And there's also studies from the US, for example, that show really nice benefit of the HPV vaccines in the age group 27 to 45. And so when that study came out, I believe I was 39 and I decided that I would still want to get vaccinated with the HPV vaccine. So I got vaccinated when I was 39. And again, up to the age of 45, there seems to be a benefit. There's now plenty of studies out on the effect of HPV vaccines and it turns out that these vaccines give long lasting protection. They had in some countries really huge impact on whole generations. In Scotland, for example, there's a nice data on that. And one has to keep in mind, these vaccines have a huge impact on the individual, right? If somebody gets cancer, that's terrible, that's really bad for the individual, not just from a health perspective, but also from a psychological perspective and the quality of life perspective, even if the cancer can be cured. But you also have to see the big picture. Serbical cancers are relatively common and they have big strain on public health and they have a huge economic impact. And if you can avoid them, you remove that strain on the public health system and you remove that economic impact. The other point that is important to know is that cervical cancer and treatment of cervical cancer can lead to issues for fertility. And so basically, getting these HPV vaccines preserves fertility and that is a good thing too. And India has started a few days ago to make HPV vaccination available for free. I think even Prime Minister Modi was promoting that and was saying that they will do that now. And I think that's a very big step forward because of course India is a very big country and they didn't have free access to HPV vaccination so far. And it also has a wise decision because this will very positively impact on public health in this country. Just to mention that the HPV vaccine was the second vaccine that protects against cancer. The first anti-cancer vaccine was the vaccine against hepatitis B virus. Hepatitis B virus infections caused liver cancer and so that vaccine was developed before the HPV vaccine and so that was the first anti-cancer vaccine. So that's it for today. In my opinion, HPV is a very important topic specifically because these infections have a high impact but they can also be mitigated by vaccine. People should know about that. As always, thanks for listening in. If you have any questions or comments or suggestions, please write an email to
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