In 10 seconds? Certain ‘types’ of Human Papillomavirus (HPV) cause cancer by messing with our cells’ growth and survival signals. Now that we know how it works, scientists are working out ways to develop more effective treatment options for cancer patients.
OK, we’ve been talking about HPV in this series for a while… care to give me a quick 101 on viruses? Sure, buckle up for a fast virology lesson, to get a better grasp on how HPV works. So: viruses are sophisticated but simple beings. Anatomically, they are just a piece of genetic code (DNA or RNA–that gives instructions on how to make more viruses) that is packaged in a way that allows it to disperse and infect specific target cells. The different strains of a certain virus are characterized by differences between their genetic codes–which translate into different ‘flavors’ of the viral proteins that they encode (You might compare a virus ‘strain’ to a dog ‘breed’). To that point, there are over 200 strains of HPV, but only a handful of them cause cancer.
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Yay, at least some good news! So what makes the difference? It turns out that some of the types of HPV, which we dub high-risk HPVs, encode viral proteins that can kick our cells into overdrive and then seize the emergency stop button and chuck it into the trash can. Meet the two troublemakers, HPV E6 and E7 (E = early because researchers noticed HPV starts using these proteins early after infection). These viral proteins evolved to help HPV survive and replicate in the cells they infect–but they do that almost too well, to their own demise (and ours as well!).
Wait, can you explain how they help HPV replicate? Of course! For HPV to replicate and spread, it must infect a specific cell type called epithelial cells (Think: skin and the linings of most of our organs). In healthy bodies, epithelial cells will naturally divide to replace older cells (AKA split into new 'daughter' cells). But after it infects someone, HPV doesn't want to wait around for that to happen in order to complete its life cycle. So HPV uses one of its proteins, E7, to promote our cells to start multiplying. It does so by removing an important cell division brake, called pRb.
What about E6? I thought you'd never ask! When our cells get pushed into overdrive by HPV’s E7 protein, they start exhibiting stress signals which would normally flag our cells’ ‘emergency stop button’, p53, to initiate a self-destruct protocol. That’s where E6 comes in. E6 removes p53 from the picture, which then allows for the cell to survive the stress and for E7 to seamlessly induce cell division without deadly consequences.
So that’s how the cancer forms? There's more. HPV's genetic code is made out of DNA, just like ours. Usually, when HPV infects a cell, it prefers to keep its genome separate from our DNA. However, in rare cases, just due to the random forces of physics, the HPV DNA can become integrated into our genome. This is where the danger happens, as the vast majority of HPV-associated cancers have somehow integrated the E6 and E7 gene segments from HPV into their own genomes. Unlike other viruses that purposefully integrate into our genome (like HIV), this is not a deliberate action by HPV and doesn't assist in its mission to replicate at all!
So that’s when the cancer starts? Not quite yet…I’ve told you cancer is complex! Just integrating E6 and E7 into a cell’s genome isn’t enough to start cancer. Additional mutations need to occur randomly and in strategic places for cancer to form.
Dang. That is complex. Does anything else need to happen? That’s it for now. To recap: HPV-associated cancer formation depends on getting an infection with one of a select few HPV strains that have ‘high-risk’ features, which must then escape our immune systems long enough to rely on a random and unintended DNA integration into the our genome in a way that helps promote the function of E6 and E7. And then this cell must randomly accrue more mutations that allow the cell to grow out of sync with the rest of our bodies and into cancer.
I hope there’s not a quiz… Sorry…I know that’s a lot. But it’s fascinating! If it weren’t such a prevalent cancer, you’d barely think it was possible. But 46,143 HPV-associated cancers occur each year in the US (25,719 in women, mainly cervical cancer –and 20,424 in men–mainly head and neck cancer)! And luckily, most high-risk HPV strains are preventable by vaccination.
HPV virology: from basic to bedside
Whether or not you think virology is as cool as I do (but how can you not), the countless hours of biochemistry performed in labs that helped us learn about all of this have paid off for patients.
Cancer researchers are always looking for unique ways to target cancer while keeping healthy cells safe. It turns out that E6 and E7 serve as unique cancer targets for HPV-associated cancers.
Stay tuned to learn about the crafty ways scientists are targeting HPV E6 and E7 to help get rid of HPV-associated cancers for good.
Dr. Talia Henkle has distilled 3 research papers, saving your 10.5 hours of reading time
The Science Integrity Check of this 3-min Science Digest was performed by Dr. Jacquelyn Bedsaul
