I have two problems with the title of this video.

First, things don’t really cause cancer. Like, imagine the most carcinogenic thing you can.

Hopefully you are currently imagining  smoking a cigarette right now, because that is the most  cancer-causing thing humans do. Most people who smoke cigarettes for their  whole lives will never get lung cancer. Now, their risk is DRAMATICALLY increased,  and also there are a ton of other bad health outcomes so,  like, don’t smoke cigarettes!

But in the strictest sense,  things do not cause cancer. Our bodies are too smart for that. Things increase our risk of cancer.

Second, since being diagnosed  with a cancer myself, I’ve been working hard not to refer  to cancers as a single disease. We really shouldn’t be saying cancer,  we should be saying “cancers.” So the title should probably be more  like, “Does infection with the SARS-COV-2 virus increase subsequent  risk of malignant carcinomas.” Or, if we wanted to be brief,  “Is SARS-COV-2 oncogenic.” But fewer of you would have clicked on that and this is super important information,  so we’re doing what we’re doing! Why is it important?

Well, because regardless of how you ask the question, it’s starting to look like the answer is “yeah. Yeah, COVID might increase your  chances of getting cancer.” But before you break out into a cold sweat, there is a lot of complexity that you  should know about that simple answer. [♪ INTRO] Just to be super up-front about  why I want to talk about this, it’s because as soon as “COVID might  cause cancer” becomes a common idea, it’s going to be followed by an  absolute buttload of misinformation. So what I want to do is less establish  whether COVID for sure causes cancer, and more show how we’re  going to be able to recognize that this is the case and how  much it’s going to matter.

Even though I just said nothing “causes” cancer, some viruses tiptoe right up to that line. Human papillomavirus, or HPV, has a strong link to cervical  cancer and other cancers. The HPV vaccine has dramatically  reduced the rates of cervical cancers in places where it is commonly administered.

So this would definitely not be the  first time a virus caused a cancer. That’s actually extremely common. Worldwide, around 10% of  cancers would not have occurred without a virus kicking them off.

The cancer I was diagnosed with,  Hodgkin lymphoma, is caused, in part, by infection with Epstein-Barr virus, which  is the virus that causes mononucleosis. A lot of you might have just gotten  worried because oh man, mono? I’ve had mono, I must be doomed.

But more than 90% of Americans are  infected with Epstein-Barr virus at some point in their lives, and  only 0.2% will get Hodgkin lymphoma. Our statistical and biochemical  understandings are sophisticated enough that we were able to first start to  understand that link back in the 1970s, which is pretty amazing! But the risk of getting  Hodgkin lymphoma doesn’t peak until four or five years after initial infection.

And with HPV, it can be fifteen or twenty years between initial infection and the onset of cancer. At the moment, no one is ten or twenty  years out from a SARS-CoV-2 infection because it’s only been out there  in the world for four years. And that’s a problem, because if  there is a connection between COVID-19 and any kind of cancer, we’d have  to watch people get sick with COVID, and then develop a particular kind of cancer.

That’s a waiting game, which is no fun for  anyone – the scientists or the patients. But it’s important to say, so far… we haven’t seen an increase in cancers  that would be easily explained by COVID. If the effect were super fast and super big, we might be able to have seen it by now.

But we also can’t just look at people  who got a serious COVID infection and see if they were more likely to get cancer. Because, look, a person who gets  serious COVID might very well develop cancer afterward because likely  the biggest risk factor for a serious case of COVID and the biggest risk factor  for cancer are the same thing: age. Lots of things could increase both the  risk of a serious case of COVID and the risk of cancer, and it’s very  hard to tease out all of those details!

But there is one thing we can do  to try to peer into the future and see if there’s a causal  connection between COVID and cancer. There is some limited evidence  for genetic risk factors that increase your susceptibility to COVID. And those genetic risk factors, if they exist, would not increase your risk of getting cancer.

They would only increase your  susceptibility to COVID infection. So! You can look at a very large  population and see that folks with those suspected genetic risk factors for COVID  have a higher chance of getting COVID.

And then you can look at that  same population and see if people with those same risk factors have gotten  more cancers in the last few years. This type of study is called a  Mendelian randomization study, after that guy with the pea  plants, and it’s sort of a shortcut to figuring out causal links between  risk factors and disease outcomes. And we did find one that claimed to  have found a causal link between COVID and cancer, but it wasn’t…like, a great study.

The study calculated the odds ratio  of the increased risk of cancer. And this is a measurement that tells  you how likely a certain exposure, in this case COVID, is to be related to a  certain outcome, in this case, a cancer. An odds ratio of one means it’s basically 50/50, no association between the two things.

Odds ratios can go below one, that means that something decreases  the risk of something else. On the other hand, the higher they  go above one, the higher the risk. This paper only reported one odds ratio above 2.

And that was for stomach cancer – the  odds ratio for an association between infection with the virus and  stomach cancer was about 2.9. And even that is kinda low, like, the odds ratio for cigarettes and lung  cancer is around 8 at minimum, and that’s for people who’ve ever  touched a cigarette, not heavy smokers. So these odds ratios just… aren’t  enough to get worked up about yet.

There is another way to look at this,  though, and one that is actually easier to investigate at this early stage where  we don’t have many years of cancer data. Basically, we can pull the virus apart  and ask whether it’s doing anything likely to tip our cells toward cancer, which  doesn’t for sure answer the question, but it lets us keep an eye out. So, the first question is, why  do viruses cause cancer at all?

And the answer is… because it helps them. Some viruses are pretty brute force. It’s the traditional virus story.

They turn your cells into virus factories  until your cell realizes something is wrong and blows itself up, and then more virus  particles get released into your body to infect more cells. But other viruses have evolved  to keep some of your cells alive as little viral reservoirs. This is what HPV does.

Your cells have all kinds of ways to  check for damage and then send out a signal for the cell to destroy  itself if things look weird. But that would be bad for the virus, so  HPV has evolved ways to dampen the cell’s ability to check for DNA  damage and to destroy itself. That means a longer-lived, more  active reservoir for viruses.

But one of the main traits of a  cancer is that it is a group of cells in your body that are worse at repairing DNA and good at conveniently ignoring  orders to destroy themselves. So the virus has evolved in order to do what  is good for the virus, but that also just happens to take a cell a few steps  closer to potentially becoming cancerous. Which increases your individual risk, and also increases the total number  of cancers in a population of people.

The question is, then, does the SARS-CoV-2 virus mess with cells in this way and, yeah,  it’s starting to look like it does. One of the most important tumor  suppressing genes in your body is p53. It does exactly what we’ve been talking  about: it helps your cells check DNA for damage and can signal a cell to  destroy itself if things are looking weird.

People who inherit only one functional  copy of this gene from their parents are extremely likely to get multiple  cancers early in their lives. Researchers have observed that SARS-CoV-2 has been shown to lower the  amount of p53 in a person’s cells. In one 2022 report, researchers looked  at blood samples from COVID patients with mild, moderate, severe, or critical  infections, including some with long COVID.

In patients with mild or moderate infections,  their blood had lower levels of p53 16 weeks after infection,  but it bounced back by 24 weeks. But patients with severe or critical  infections didn't have that bounceback. Their p53 levels were still low after 24 weeks.

And it’s not just low, it’s actually  worryingly low - the researchers specified that if the reduction in p53 function continues, it could be just as bad as a mutation  that causes it to lose function. Less P53 means that the cells are less  able to fight the COVID infection, but it also means that they’ve been  pushed a little further down the path to potentially becoming a cancer. A brief dip in p53 levels probably  isn’t anything to worry about.

But the longer you go without, the  more the risk of cancer increases. But while p53 is a big deal, there’s plenty  more that might be going on here too. For example, the SARS-CoV-2 virus  interferes with something called the RAAS system, which regulates blood pressure, and results in increased activity  of a protein called angiotensin II.

Angiotensin II is itself associated  with more aggressive cases of a certain type of lung cancer. But it also can switch on all  kinds of pro-growth signals that cancer cells slurp up like candy. On top of that, infection with the virus  appears to disrupt normal cell division, causing mutations and pushing cells to divide even when normal checks and  balances would stop them.

Based on the molecular pathways it  alters and the organs it affects, researchers suggest we should  keep a particular eye out for lung, colorectal, pancreatic,  breast, and oral cancers. At this point, it is looking like it  is possible that the SARS-CoV-2 virus increases the risk of certain cancers. But there are much more important,  bigger questions that remain unanswered, like, what’s actually going  to happen, when, and to whom?

We live every day with almost everyone  in this country getting a cancer-causing virus, Epstein-Barr, and we  simply don’t think about that. I mean, I don’t. Some people do, though, and a vaccine for  that virus could save thousands of lives a year and there are people working on one!

Which is great, because  Epstein-Barr also increases a person’s risk of multiple  sclerosis by around 32 times. One last thing here. You may have heard that rates of  some cancers among young people, especially colorectal cancer,  have been recently increasing.

And indeed, rates of colorectal  cancer in people between the ages of 35 and 45 have been increasing  substantially, basically doubling since 1995. This is a long-term trend, but it only  really hit the news in the last few years. We’ve seen people wondering online  if this increase is because of COVID and just wanted to add at the end here  that this trend significantly pre-dates the emergence of the SARS COV-2 virus and the causes of the increase remain unclear.

Some of it is probably just because people getting more face time with their doctors. In fact, right before the pandemic began, a report came out that showed people  were spending more time with doctors... and when you spend more time with doctors, you find more diseases and  disorders, including cancer. COVID is, in some ways, the  most studied virus in history, but the reality is that we will need  more time and more research to understand the significance of the link  between COVID and cancers.

We’ve already been able to see  rates of cervical cancer decrease after people started getting the  HPV vaccine, but that took FOREVER. As with many things in science, the more  we know, the more questions we find. And we have not found a DRAMATIC  link between COVID and Cancer… but we have found a potential link.

It’s not cigarettes, but is it nothing? Let’s put it somewhere between  cigarettes and nothing. And drilling deep on this virus has been  extremely effective in helping us better understand cellular and viral phenomena,  but it might also help us understand our bodies more broadly, and  the diseases that befall them.

Knowing more is always good, even if what we find is not as  comforting as we might like. This video was brought to you  by our patrons on Patreon. They are an amazing group of  people who help us make this show.

About, like, 1.5 out of every  10,000 people who watch SciShow actually give us a little bit of money, and  they are the whole reason we can do this. Big thank you to all of you, and  also thanks to everyone for watching. [♪ OUTRO]