DrPal, tell us more about HPV and cancer

OK, if you insist. This comes with the usual caveat directed at scientists that I know this is oversimplified, but I wish to reach the largest audience possible. Feel free to correct my mistakes, but please don’t bother me about oversimplification.

So here’s the deal. Several decades ago, it became scientifically fashionable to believe that most cancer had a viral cause. This belief coincided with the discovery that some viruses do cause cancer. And while it turns out that most cancers are not caused by viruses (probably), many of them are. Viruses can cause cancers in a number of ways, but since you said you were interested in HPV (human papilloma virus) we can use this as an example.

First, there is no scientific question about the causal relationship between HPV and cervical cancer (and certain oral cancers, anal cancers, and penile cancers, but we’ll use cervical cancer as shorthand for all of them). There is excellent epidemiologic evidence to support this, and virologic evidence that proves it.

Now that we’ve got that out of the way, how does this cancer virus thing work?

First of all, we need a very basic understanding of what “cancer” is. Cancer refers to hundreds of different diseases that have one thing in common—uncontrolled growth of cells that are no longer restricted to their usual place of residence.

For cells to be “cancerous” they must lose their ability to die off in the usual way. This allows a mass of cells (which are clonal, meaning they are all daughter cells of an cancerous mother cell) to continue to divide and to fail to die. Cell division increases the population of cells, and forgetting to die prevents a reduction in the population. In addition to this, a cancerous cell has gained the ability to escape its usual home, that is it can grow out of the space this type of cell was designed for.

So, for example, in colon cancer, a particular type of colon cell my sustain a genetic injury that causes it not to die at the proper time, and another that allows it continue to divide and produce daughter cells. As this goes on, more mutations can accumulate, until a fortuitous one allows the cells to grow beyond the inner wall of the colon and invade the deeper layers. Eventually, these cells may even gain the ability to break free and thrive in distant tissues (“metastasis”—in the case of colon cancer, to the nearby lymph nodes, and then the liver).

This is the “Knudson Two-Hit Hypothesis” (or the more modern “multi-hit hypothesis”). A cell needs a defect causing immortality, and another causing uncontrolled division. Many genes involved in this process have been identified. Two broad classes of the genes involved in cancers are tumor-suppressor genes and oncogenes. TSGs are genes that normally prevent uncontrolled cell division—they regulate the cell cycle and tell a cell when it is or is not appropriate to reproduce. Oncogenes, on the other hand, stimulate cell growth in a variety of ways. These two classes of genes create a balance as the brakes and accelerator of cell growth. When one is damaged, the other can still control cell growth, but when both are gone, cell growth goes unabated.

What? HPV?

Oh yeah, sorry. Let’s get back to HPV.

The strains of HPV that cause cancer are rather interesting. They produce a protein that inhibits the products of the powerful tumor suppressor genes Rb and p53. That’s one hit, which helps to explain why only a minority of people with HPV actually get cancer—they still need that second hit. We aren’t sure yet what constitutes the second hit in cervical cancer, but there are lots of candidates.

So HPV causes cervical cancer by screwing with two of our most powerful tumor suppressor genes. The rest in commentary. Go and learn it.

Related Links (which I was too lazy to embed)

http://whitecoatunderground.com/2008/01/29/hpv-and-cervical-cancer/

http://www.brown.edu/Courses/Bio_160/Projects1999/hpv/path.html

http://virology-online.com/viruses/Papillomaviruses3.htm

http://www.cinj-genetics.org/health_pro/health_pro.htm

http://jncimono.oxfordjournals.org/cgi/content/full/2003/31/35

Comments

  1. #1 John S. Wilkins
    August 14, 2008

    It affects men too. I am lacking my left index finger below the first joint due to a HPV induced cancer.

  2. #2 PalMD
    August 14, 2008

    I did make mention of it above. I do hope gardasil will be made available to boys up here in the US, for a variety of reasons. Perhaps another post will discuss epidemiology,etc. Thanks, apeman.

  3. #3 Becca
    August 14, 2008

    Gardasil is available for boys in the US: I had both my son and daughter vaccinated with it when it first came available. and, to my shock and (pleased) astonishment, our insurance paid for them both.

  4. #4 Chuck
    August 15, 2008

    How many forms of cervical cancer are not facilitated by exposure to HPV?

  5. #6 PalMD
    August 15, 2008

    PWNED1!!!11!

  6. #7 Laina
    August 15, 2008

    Re: second hit. Telomerase activity (only with integration)

    Pett, M., Alazawi, W., et al. 2004. Cancer Research. Acquisition of High-Level Chromosomal Instability Is Associated with Integration of Human Papillomavirus Type 16 in Cervical Keratinocytes. 64: 1359-1368.

    http://cancerres.aacrjournals.org/cgi/content/full/64/4/1359

  7. #8 PalMD
    August 15, 2008

    Most of the oncogenic strains do integrate….but wait, that’s science…couldn’t it just be evil spirits? Maybe we need less vaccination and more exorcism.

  8. #9 Laina
    August 15, 2008

    Sorry for commenting so much! I am just fascinated by HPV and love sharing information about it

    More on telomerase activity:
    “E6 increases telomerase activity in keratinocytes through increased transcription of the telomerase catalytic subunit gene (TERT)”
    http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12941894

  9. #10 LanceR
    August 15, 2008

    Yay, Laina!! Don’t apologize. Anyone who can spank a troll that quickly deserves our respect.

    We’re not worthy… we’re not worthy…

  10. #11 Rogue Epidemiologist
    August 15, 2008

    Those are great links, Laina. Thanks for posting them.

  11. #12 MobiusKlein
    August 15, 2008

    Not sure (from this page alone) that ‘Chuck’ was trolling – asking how many cancers come from HPV is a valid question.

    It may be a bit confusing because ‘forms’ of cancer is a different number than ‘instances’ of cancer. There could be a large number of very rare forms that comprise a tiny % of overall cancers.

  12. #13 Laina
    August 15, 2008

    I don’t think he was trolling, either. I was just answering his question. I also didn’t know the exact percentage, so this gave me an opportunity to do some research, too! Thanks for sparking my curiosity, Chuck!

  13. #14 Dan
    August 15, 2008

    Caveat, I am not a doctor and I do not play one on TV. PalMD, if your intended audience was me, well then well written.

  14. #15 Meaghan Edelstein
    August 16, 2008

    I am a Stage 3B Cervical Cancer Survivor. I created a blog in an effort to raise Cervical Cancer Awareness http://www.cancerlost.blogspot.com. I was 28 when I was diagnosed with advanced Cervical Cancer and my story is a long, painful & inspiring one. Cervical Cancer is not talked about but it touches the lives of every single woman out there. We need to start talking about this cancer because it is not rare and it does kill.

    http://www.cancerlost.blogspot.com

  15. #16 PalMD
    August 16, 2008

    Amen, sister.

  16. #17 Jeb, FCD
    August 16, 2008

    What happens if someone is vaccinated and they have already acquired an HPV covered in the vaccine?

  17. #18 Laina
    August 16, 2008

    Well, if you only have one of the four types covered by the vaccine, you will still benefit from being protected against the other three. If you have all four types, I don’t think the vaccine can be of much use to you, although I’ve seen data that suggests that the vaccine (unintentionally) also protects against several other types of HPV. However, because the four types of HPV covered by the vaccine are the four most problematic types (two that account for most cases of cervical cancer, and two that account for most cases of genital warts), the benefit may not be that great, because it is far less likely that other strains will give you nearly as much trouble as the strains that you are already infected with.

    Is this right, PalMD?

  18. #19 Bill
    August 16, 2008

    So is gardasil proven to work for males as well as females?

    I’ve read conflicting things about this. I’m surprised with the lack of clear information that is out there about some of these vaccines.

  19. #21 Noticed
    August 17, 2008

    Thank you for this clear article.

    I was just a few years too old to receive the Gardasil (they cut it off at 26). Anyone know about whether or not it will become available for those of us over 26?

    Thanks.

  20. #22 Rogue Epidemiologist
    August 18, 2008

    @Noticed
    If you ask really nicely and offer to pay out of pocket, I’m sure you can find a doctor to give you Gardasil though it’s technically “off-label.”

    People tend to contract HPV in their teens and early 20s, so from a statistical standpoint, if you haven’t picked up HPV by the age of 27, you’re probably not going to get it. I know … that’s faulty logic. Some of us are dweebs and spazzes and never got around to dating until we were a bit older. But I can only guess they were trying to be cost-effective.

    With that said, I noticed on http://www.clinicaltrials.gov that there were some studies underway to examine the benefits of Gardasil in older women.

  21. #23 Brianna
    October 3, 2008

    This is a great post! It cleared up the questions I had with the first post. It does kind of make sense that cancer is linked to viruses because if a human were to have a virus, and not treat it for a while it gets worse and normally leads to something larger. Unfortunately, in some cases, it leads to cancer.

    Do you think cancer can be avoided?

  22. #24 Me
    December 12, 2009

    I was diagnosed with an HPV (of the lovely wart variety) at 35 (which is when I contracted it). My second partner gave it to me while being asymptomatic himself, and feels horrible about it. Guardasil likely would have prevented this, but being that I was over 30 when it went on the market, I was not encouraged to get vaccinated, even though I knew I was not exposed by my first partner. My doctor did tell me that she does vaccinate women who are older- she does see this occur, but the women need to ask. It does make me sad that we are not vaccinating boys because we, as a society, feel “it’s not their problem.” I also think we are going to look back at the half population vaccination as a mistake, and ineffective.

  23. I think the problem today with the growing HPV trend is that most people have no idea they have it. The public is not entirely aware of just how crucial the problem is and what contributes to it. The Internet is an important contributor to facts if you can wade through the garbage posts and nonsense that people put up.

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