#4 – Human Papillomavirus: Why Vaccination Matters

00:00:06: And these viruses are very, very common.

00:00:08: Right?

00:00:09: So at the age of fifty about eighty percent people have been exposed to them.

00:00:14: so it's not something that some people have and if you're lucky or never get it... ...the chances are very high during your lifetime when you get infected with HPV.

00:00:39: Virological.

00:00:40: With Florian Kramer Hello!

00:00:52: Welcome in this week episode of ViroLogical.

00:00:56: This was recorded on March second of twenty-twenty six in Oulu, Finland.

00:01:04: And today we're going to talk about the human papillomavirus.

00:01:07: Why is this called Papilloma virus?

00:01:09: Because these viruses can cause warts and warts are also called papillomas... ...and that's why they named like that.

00:01:18: Papillomaviruses are very diverse there large group of viruses that infect many different species so not just humans, but many other species.

00:01:29: And in terms of human papilloma viruses they're also very diverse.

00:01:32: we have more than two hundred types in humans and Not all of them are widespread...not all of the are problematic But some of them cause warts ...and Some of them caused cancer.

00:01:43: so people should know about them.

00:01:46: Human Papilloma Viruses are DNA viruses.

00:01:49: They have a double-stranded circular DNA genome And in this case you have the double-stranded DNA genome on the inside of the particle.

00:01:59: Then, it is covered with histones and then... The virus doesn't have a lipid envelope.

00:02:06: so its just a capsid shell that we had from outside.

00:02:12: And interesting part are these capsid shells are very regular made out two proteins an L-II protein, that is the minor component.

00:02:22: And then we have a L-I protein.

00:02:24: and so this L- I protein comes together spontaneously to form bentomers.

00:02:29: So five of these proteins come together to form one bigger structure... ...and then seventy two of these bentomeres come together.

00:02:38: It's specifically seventy two and they basically assemble into a virus particle.

00:02:44: That's happening because when the protein basically assembles first into these pentamers and then in to particles that have this seventy-two units, the state of proteins achieve thermodynamic minimum.

00:02:58: And it is by itself assembled.

00:02:59: as this process The particle itself has about sixty nanometers in diameter.

00:03:06: These particles are relatively stable in terms of pH temperature more than many other viruses and that of course helps them spread.

00:03:15: Papilloma viruses were first discovered by Richard Chope, who was a U.S.

00:03:20: virologist And he made the association between papilloma virus and words developed in rabbits infected rabbits In nineteen thirty two.

00:03:33: As already mentioned there are about two hundred types of human papillomal viruses.

00:03:38: These viruses have been in humans for long time So you might be aware but People like Swan the Babel, for example developed techniques of how to sequence ancient DNA from old bones.

00:03:50: For example.

00:03:52: and they have done this with Neanderthals for example right?

00:03:57: And so the genome of neanderthal has been basically elucidated and assembled from DNA fragments from their bones.

00:04:05: but in these data sets people also found genomes of human papilloma virus.

00:04:13: I mean that's DNA, it had also survived and could be sequenced.

00:04:17: That means the Neanderthals already have human papiloma viruses.

00:04:22: It is very likely that Stone Age humans has already had human papilla virus infections.

00:04:28: So its not really clear how long this virus was in humans probably for a very long time, it's very likely that the virus co-evolved with humans.

00:04:41: What is interesting about these viruses are they don't cause symptoms.

00:04:45: we typically associate with viral infections where you might get fever or other symptoms that show that you're infected.

00:04:54: That's not the case with human papilloma viruses.

00:04:57: These viruses are mostly transmitted by sexual contact.

00:05:01: Most often end up on the mucosal surfaces of their reproductive tract but also in other areas, other mucousal surfaces.

00:05:10: But some of them when they end up with skin and regular skin can infect the skin.

00:05:16: so once we come into contact with them they bind to receptors on cells as I said most on these mucosa surfaces.

00:05:25: those are often special cells that infect epithelial or basal cells and they start to infect these cells, but this viruses have a problem.

00:05:34: They don't have their own polymerase so they do not have an enzyme that copies the genome.

00:05:39: And in order to grow we need DNA polymerases of our host cell.

00:05:46: So we need active DNA polymerase.

00:05:50: But most of us are not growing, they are terminally differentiated.

00:05:57: They're just cells in the body but don't grow much and so they have a lot of this DNA polymerase activity.

00:06:02: And that's problem for the virus because it goes into cell then the genome gets not copied right?

00:06:08: The virus can't grow!

00:06:10: Unfortunately the virus has overcome that.

00:06:13: It expresses number of proteins, most prominent ones are E-six and E-seven proteins.

00:06:21: And basically the virus forces cells to start multiplying and proliferate.

00:06:28: When that happens, DNA activity is high which means also the genome of the virus gets copied or multiplied... ...and this allows them to grow.

00:06:36: Now here's an issue!

00:06:38: These cells are not supposed to grow but when they start growing unregulated it can lead to the formation of warts as well as cancer.

00:06:50: That's why these viruses are really problematic.

00:06:54: We know that certain types of human papilloma virus cause certain issues, we know that HPV six eleven but also thirteen forty and forty three caused genital warts.

00:07:10: Dipes one two four twenty seven or fifty-seven for example causes warts on skin so regular skin.

00:07:18: And of course nobody likes warts, especially nobodies like genital warts.

00:07:23: But these viruses are not a problem in terms causing severe disease or death but there's other types and specifically type-sixteen, eighteen...but also thirty one, thirty three forty five and so on and so forth are worse because they cause cancer.

00:07:43: And we know that type XVI is responsible for about fifty percent of all cervical cancers, and type XVIII is responsible approximately twenty percent.

00:07:57: So this connection between cervical cancer and HPV was discovered by Harald Zuhausen in the nineteen eighties and he got a Nobel Prize for that discovery.

00:08:13: And so, important thing to realize is these viruses can be transmitted by not just women but men and women.

00:08:23: they can infect man and woman.

00:08:25: They can cause cervical cancer in women But it also causes anal cancer and head and neck cancer both sexes.

00:08:37: These viruses are really problematic.

00:08:39: They're not just a problem for women, they also have problems with men and circulation of these viruses typically begins when people become sexually active.

00:08:51: so the highest prevalence of HPV in population is between fourteen to thirty but you can find them all age groups.

00:09:02: that has lower prevalence.

00:09:03: What often happens.

00:09:05: one gets infected and then the immune system actually clears the infection relatively quickly before the virus can do a lot of damage.

00:09:13: But that's not always the case, in many cases infections last for months sometimes four years.

00:09:19: it becomes basically persistent infection.

00:09:24: there is this saying that HPV infections lasts usually longer than their relationships.

00:09:29: The problem is when infection persists and the virus starts to infect many cells, then the risk increases that some of these cells become cancerous.

00:09:41: And this viruses are very common right?

00:09:43: So at the age of fifty about eighty percent people have been exposed to them.

00:09:49: so it's not something that some people have and if you're lucky or never get it... ...the chances are very high during your lifetime with HPV.

00:10:00: As I said, there is a high risk for cervical cancer in women but also the risk of HPV-related head and neck cancer that has been rising over the last decades.

00:10:16: The good thing about this is something can be done about it.

00:10:19: Vaccines have developed and licensed in the two thousands.

00:10:24: These vaccines are based on virus like particles.

00:10:27: they're made with a trick.

00:10:30: I was talking earlier about this L-one protein that forms most of the virus capsid.

00:10:37: And they told you all about their self assembly and thermodynamic minimum, right?

00:10:42: So it turns out when you express these L one recombinantly different cell types, different expression systems... ...and you purify it also self assembles into particles.

00:10:55: They look just like HPV, but they're empty inside.

00:10:58: You don't have a genome and we call this virus-like particles And so the immune system recognizes them and makes neutralizing antibodies when it sees them.

00:11:10: But you can do anything because there is no genome that can do any harm.

00:11:14: That's their beauty.

00:11:16: One of these vaccines called Cerberics contains HPV types, sixteen and eighteen.

00:11:22: So remember those are the high-risk ones for cancer.

00:11:26: And this vaccine is attumented with ASO four.

00:11:30: that's just an adjuvant That increases the immune response to it.

00:11:35: This is a vaccine that has two high risk types.

00:11:38: This is made in insect cells.

00:11:40: That sounds strange, but it's basically the same way how the Novavax COVID-IX vaccine was made.

00:11:46: so insect cells are a common production system for vaccines.

00:11:50: Another vaccine that was developed is called Gardasil and this is actually made in Bakers yeast, so Saccharomyces cerevisiae.

00:11:58: So you can also make recombinant proteins, recombinate antigens In bakers yeast And then purify that and use that as a vaccine.

00:12:08: Gardasil is quadrivalent, that means it has four components.

00:12:12: It has type XVI and type XVIII so the high-risk cancer ones.

00:12:17: but it also has type VI and type XI.

00:12:19: those are the ones causing most genital warts.

00:12:24: And then there was a new development called Gardasil IX.

00:12:28: So that's nine valents.

00:12:29: There're nine components in here.

00:12:31: Here we have type XIV and VIII The most dangerous one rarer types that also cause cancer, including type thirty-one, type thirty three, type forty five, type fifty two and type fifty eight.

00:12:47: And in addition we have type six and eleven which are the ones to cause genital warts .

00:12:52: So this vaccine gives a very broad coverage.

00:12:55: it has an efficacy of over ninety percent for prevention of cervical cancer.

00:13:01: In total there now six vaccines that are WTO qualified Basically, potentially globally available.

00:13:11: Although there are some countries that haven't implemented them other countries have active vaccination campaigns with them and they'll get to it in a minute.

00:13:20: Of course its best to vaccinate before sexual contact start.

00:13:26: Many countries basically recommend vaccination between age nine and age fourteen And then basically infections are prevented.

00:13:36: It's also important to mention that girls and boys should be vaccinated because while the risk for cancer is higher in girls, boys spread the virus too.

00:13:45: And if they're vaccinated you don't spread it... ...and that reduces the risk in general.

00:13:49: So typically its best if we give this vaccine to teenagers or pre-teenagers but has been shown as very helpful when people who are in their twenties or thirties get vaccinated.

00:14:05: fewer infections there because many people at that point already had been infected with HPV, but it still has an effect and is very advantageous to get the vaccine.

00:14:17: There are also studies from US for example which show really nice benefit of the HPV vaccines in age group twenty seven-to forty five.

00:14:27: When this study came out I believe i was thirty nine and I decided that i would still want to get vaccinated with the HPV vaccine, so I got vaccinated when I was thirty-nine.

00:14:38: And again up to age forty five there seems to be a benefit.

00:14:44: There's now plenty of studies out on the effect of HPV vaccines... ...and it turns out these vaccines give long lasting protection.

00:14:54: They had in some countries really huge impact on whole generations.

00:15:01: in Scotland for example, there's nice data on that.

00:15:04: And one has to keep in mind these vaccines have a huge impact on the individual right?

00:15:10: If somebody gets cancer thats terrible!

00:15:13: Thats really bad for an individual not just from health perspective but also from psychological perspective and quality of life perspective even if they can be cured.

00:15:25: But you'll see big picture.

00:15:28: cervical cancers are relatively common.

00:15:31: They are big strain on public health and they have a huge economic impact.

00:15:36: And if you can avoid them, then remove that strain from the public-health system... ...and remove their economic impact.

00:15:43: The other point important to know is that cervical cancer in treatment of cervical cancer can lead to issues for fertility.

00:15:52: Basically getting these HPV vaccines preserves fertility.

00:15:57: That's good thing too And India has started a few days ago to make HPV vaccination available for free.

00:16:07: I think even Prime Minister Modi was promoting that and saying they would do it now, but i think this is very big step forward because of course india is a really big country with no free access to HPV vaccinations so far.

00:16:22: It's also a wise decision as this will positively impact on public health in the country.

00:16:28: Just to mention that the HPV vaccine was the second vaccine, which protects against cancer.

00:16:35: The first anti-cancer vaccine is the one against hepatitis B virus.

00:16:39: Hepatitis B infection causes liver cancer and so this vaccine was developed before the HBV vaccine.

00:16:50: That's it for today!

00:16:51: In my opinion an HPV is a very important topic specifically because these infections have a high impact but they can also be mitigated by vaccine.

00:17:01: People should know about that!

00:17:03: As always, thanks for listening in.

00:17:05: if you have any questions or comments or suggestions please write an email to Virological at podcastwerkstatt.com and If you like the podcast You can support it on Steady.

00:17:17: Thanks a lot Bye And don't forget to follow and leave a review on your favorite podcast app.

00:17:53: Podcast Werkstatt!