Cancer Research
5:00 am
Thu July 10, 2014

Seattle Scientist Trying To Disrupt HPV, Which Hacks Your Cells To Cause Cancer

The human papillomavirus is a bit like a tiny hacker — black hat, of course — that sneaks into your cells, hijacks your hardware and uses it to copy itself. For nearly 80 million Americans, this is happening right now, and nearly all sexually-active people will pick up HPV at one time or another.

For a smaller number of us, that bit of forced entry touches off a chain of events that leads to cancer — mainly cervical cancer, but also penile, rectal, throat and tongue cancers. If scientists could figure out exactly how that happens, they might able to intervene and disrupt the process.

“If you're able to avoid those infections or detect and treat them before they start to lead to cancer, you have the opportunity to avoid the disease to begin with,” said Rachel Katzenellenbogen, a researcher at Seattle Children’s Research Institute and a faculty member at UW Medicine.

Katzenellenbogen recently received a $2 million grant to decipher the virus’s playbook, in hopes that scientists can figure out how to outflank it.

You’re No Good To It Dead

HPV wants to reproduce, and to do that, it needs you — alive. Katzenellenbogen says HPV wants to get somewhere where it can make copies of itself without getting attacked by your immune system, but also without killing you. You’re no good to it dead.

So HPV infects cells in skin and mucus membranes, where it takes over the cellular machinery that would normally help the cell replicate, and uses it to instead copy its own viral DNA.

While it’s in there, it disrupts a bunch of normal cell signaling (think of a hacker scrambling your security software) that would normally call in immune cells to clean out a foreign body. That lets the virus work in peace.

“Let’s say you have a cut on your finger. Within a day, where your cut is sore, red, swollen,” Katzenellebogen said. That inflammation is part of your body’s immune response, showing that it’s working to prevent or fight infection.

But say instead you have a wart on your finger, which is caused by a papilloma virus infection.

“Your body appears to not really care; it’s not red, it’s not inflamed. Your body has a very slow, and not very robust, response to a papilloma virus infection,” she said.

Cells Live Too Long

HPV also wants its little virus factory — that is, your cell — to last as long as possible. So it silences another set of signals that would normally turn the cell off. And that’s where the problems really start.

The virus can actually make the cell live too long. And like an older person who probably shouldn’t be driving anymore, an aging cell can be a dangerous thing.

“They’ve gotten broken DNA. They're too old. Their chromosomes are starting to stick to one another. And all of those are things that should be catastrophic to a cell,” Katzenellenbogen said.

But HPV actually blocks the signals that would normally tell the cell it’s time to grind to a halt or self-destruct, or let an immune cell take it out. Instead, these cells keep right on cranking out copies of themselves and of the viral DNA. Make too many corrupt copies, and you risk for some of those cells becoming cancerous.

Vaccine Doesn’t Cover Everyone

An HPV vaccine was approved in 2006, and has been rolled out widely. But its uptake has disappointed some public health authorities; just over half of girls age 13 to 17 got it in 2012 as did just 21 percent of boys. That’s quite a bit lower than most other immunizations.

Katzenellebogen recommends that all young people get the vaccine before they are sexually active. And she recommends the newer versions, which protect against more forms of the virus, including one that causes genital warts.

But generations of adults were too old to be vaccinated (immunity must be established before a person is sexually active and likely to be infected). So Katzenellenbogen hopes to find ways to interrupt the process by which HPV hacks our cells, ensuring that an infection doesn’t lead to actual disease.

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