HPV: Treatment, Research and Discovery Thinking

EDIT: More about HPV vaccine updates found here.

This will be my fifth post concerning Henrietta Lacks, the women who died in 1951 of cervical cancer and also donated her cells to scientific research.  These cells gave birth to a new technique: tissue culture.  Today, tissue culture is thriving in nearly all laboratories, including my own.

                Her story is really two intersecting tales: first, she was a woman afflicted with cancer and second, those cancer cells were a secret goldmine to scientists.

                The first post (Henrietta’s Cells) was an introduction to her, her story, and the book written by Rebecca Skloot that spurred this blog series.  The second through fourth posts concerned HPV infection and how that can lead to cervical cancer.  

I tried to break the information down in a way that would make sense to someone not intimately involved in the medical sciences.  I started with HPV infection from the point of view of a patient (HPV and Personal Reasons), then went the next step lower to show how a normal cervix changes when infected with HPV (HPV: Transitions) and finally explained what is actually going on inside the cells that makes them behave differently (HPV: The Cell).  Working the other direction, you could say I showed you how the inside of one infected cell changes (HPV: The Cell), then how those cellular changes lead to tissue changes (HPV: Transitions), which finally leads to how your body changes and what doctors must do to correct the situation (HPV and Personal Reasons).  I covered this progression in a flow chart shown in Figure 20.1.

                Before moving on to how and why these cells were so important to research, I’d like to linger on what is going on inside the cell for one last post.

                I told you that HPV messes up the cell cycle – it stops a cell from moving through all the checkpoints and dividing safely into two healthy cells.  Instead, the infected cell moves rapidly through the cycle, divides whether or not major problems exist in the DNA and essentially sets up the proteins within the cell to behave incorrectly.  Incorrectly behaving proteins leads to big problems down the line, one of which is cancer.  Its main media for messing up the cell cycle are two viral proteins, known as E6 and E7.

                Two interventions currently exist for HPV.  The first is the excision of infected cells.  Unfortunately, it can be difficult to know if you’ve cut out every single infected cell, which means that multiple Pap smears are necessary following removal.  The second is only a preventative measure: the HPV vaccine.  Yes, the vaccine is a really nice development, but it too has limitations.  The vaccine only works against some strains of the virus (not all ~ 30) so it’s not 100% preventative and it also offers no treatment for anyone already infected.

                Wouldn’t it be wonderful if there were some kind of medicine you could give a patient that would specifically target infected cells and stop E6 or E7 from messing up the cycle?  Just as antibiotics attack bacteria in our body and kill it, wouldn’t a drug to stop HPV infection and limit its effects once we came in contact with it be a huge sigh of relief?  Wouldn’t a treatment for people who don’t have access to yearly Pap smears (cervical cancer is one of the leading causes of death in woman worldwide) be such a boon for women?  What about other viruses or diseases that humans are plagued with?  

                This is what many scientists are working on.  We’re looking, I assure you!  

                How are we looking?  

                This is where ingenuity, long hours, and intimate knowledge of proteins come in handy.

                I’ve explained protein behavior in past posts as “p53 tells the cell” or “E6 deals a deathblow to p53.”  I haven’t actually explained how proteins communicate with each other.  The primary method they use is contact.  Protein A must attach (or bind) to protein B in a functional way.  They must come together in space in exactly the right orientations and with exactly the right amino acids to make a true connection.  Think of it as the difference between standing in a large crowd and having hands accidently touch versus a business handshake between two parties.  Both involve hands touching, but only one is a purposeful act.

                In the case of HPV, scientists have been trying to find ways to keep E6 and E7 from doing their jobs.  What if you could find a little molecule (which is essentially what drugs are) that would specifically bind to E6 or E7 and change its shape?  Small changes in shape will have huge effects on whether a protein can bind to another.  The smallest change can keep E6 from being able to bind p53.  If it can no longer bind p53, then it can no longer knock p53 out of the game and the cell will not succumb to HPV's attempts to deregulate it.  

                These are the types of things that scientist think about.  We have to picture the whole scene, pick out vital parts that allow it to continue and then ask “how can we stop that from happening?”  It is the same question over and over again with different diseases, cancers, infections, and medical problems.  What went wrong; how do we make it not happen again?

                Obviously, this isn’t an easy task.  Many times if we stop one thing from happening, other things will happen instead.  Ah, the butterfly effect!  To quote Ian Malcolm, “A butterfly flaps its wings in Beijing and in New York, we get rain instead of sunshine.”  These systems within our cells are connected and everything exists in a delicate balance.  

                Finding a drug that can do exactly what you want it to do, have minimal side effects, and show reproducible results in a system as enormously complicated as the human body is a true needle in a haystack.  Proving the drug's effectiveness is equally arduous.  It’s not uncommon for a drug to spend ten years in clinical trials before ever coming on the market.  Science is patience, perseverance, hard work, and lots of money.  And the scariest part about it is that no matter how hard you work, the possibility of finding the needle is incredibly remote.

                Just some food for thought about the lives of scientists…

                My next post in this series will look at tissue culture!  I also have some posts lined up on beriberi in the Australian Outback and the joys that is a scientific conference.

References

Me, myself, and I

Spielberg, Steven. (1993) “Jurassic Park.”