Down through the centuries, the presence of warts in the nether regions was thought to be an alternate expression of syphilis or gonorrhea—until the mid-1800s, when they were understood to have a distinct identity. Decades later, genital warts would finally be identified as the work of human papillomavirus (HPV).
But HPV, despite having distanced itself from the chancre-and-urethral-discharge crowd, eventually became a pariah in its own right. The evidence is now clear: HPV is the major cause of cervical cancer. Which is why millions of women stood up and cheered earlier this year when the FDA approved Gardasil, the first vaccine designed to target genital-avid types of the virus. And when the FDA also suggested that prepubescent girls be vaccinated before they become sexually active—as early as age 9—millions of parents stood up and screamed.
But that’s another story. The story I want to tell is how catching a virus can give you cancer.
There are more than 100 strains of HPV, and while all of them specialize in infecting skin cells, several dozen have sub-specialized in the groin. The cervix, its location notwithstanding, has a cellular makeup like that of skin. To understand the life cycle of HPV is to understand the life cycle of skin, its host. The dry, flaky, top layer of our skin, the epidermis, has its genesis in the deeper layers, where skin cells actively divide. As these newly formed cells mature, they rise to the skin’s surface, where they finish their brief tour of duty as part of the human shield.
After these cells are birthed, their genetic machinery is, in essence, mothballed—the cell is committed, the house is built, and the blueprints are no longer needed. This genetic shutdown, however, does not serve the interests of HPV, which needs the host cell’s gene machine to be up and running in order to manufacture copies of itself. (Viruses like HPV replicate by splicing their DNA into the host’s DNA.)
So the host cell wants to go to bed, but the unwanted houseguest wants to party through the night, procreating like crazy. To facilitate this, HPV and its viral ilk come equipped with proteins that force host cells to keep their DNA in an active phase. Big trouble sometimes follows, since DNA replication is a prerequisite not only for normal growth, but also for cancer, which, simply put, is a state of unregulated cell division.
An HPV-infected skin cell undergoes mitosis (i.e., divides in two) more often than an uninfected one, increasing the probability of malignant change—and to make matters worse, the virus keeps the host cell from dividing correctly. For one cell to properly become two, the DNA must be duplicated precisely, with the copy and the original separating cleanly and moving to their respective corners. Normal human cells accomplish this with a very low rate of errors, otherwise known as mutations. However, having viral DNA in the house can complicate the process greatly, making mutations—and thus cancer—much more likely.
If a healthy cell does make a genetic flub while dividing, there are several processes by which the newly minted mutant can be aborted or kept from further dividing. But a virus can interfere with these backup security arrangements, increasing the odds of a malignancy yet again.
All of this might lead you to think that HPV is doing everything it can to cause skin cells to become cancerous. Actually, it isn’t. Malignant transformation is not in a virus’s best interest. Cancerous cells don’t produce viral offspring—they’re too busy with their own replicative obsession. Cervical cancer is not what human papillomavirus had in mind.
Though HPV can cause cervical cancer, not every HPV infection leads to cervical cancer. Not by a long shot. HPVs can be classified into low- and high-risk groups. The low-risk types are the culprits behind the vast majority of run-of-the-mill genital warts, but they rarely trigger cancer. High-risk strains are much less common but more likely to lead to cancer. Typically, their visible effects are decidedly unwarty; the growths they cause are flat and often nearly invisible to the naked eye.
Most low- and high-cancer-risk HPV infections resolve without treatment over the course of a few years—which might feel like a decade or two, depending on how afflicted the afflicted is. In a small minority of patients, the infection can persist, and if a high-risk type is involved, this extra time can allow the bumbling HPV to haphazardly reshelve some of the books in the host cell’s genetic library. Pre-cancerous changes can occur, yielding an abnormal Pap smear. But even within this group, only a small percentage of patients will develop cancer if the abnormal cells are not treated.
So a small number of genital warts are from high-risk strains, and only a small number of those infections become chronic, and only a small number of those cause cervical cancer. I emphasize this because public medical information tends to come across as absolute. Headlines like “HPV Causes Cervical Cancer” tend to morph into “If You Get HPV, You’re Going to Get Cervical Cancer”—when, in truth, the odds are greatly stacked against that happening. There are about 5.5 million new cases of HPV in the United States each year. During that same period, about 10,000 new cases of cervical cancer will be diagnosed, and about 4,000 American women will die of the disease. The risks are real, if mathematically small.
Enter Gardasil, which targets HPV types 6 and 11 (low-risk strains that cause 90 percent of genital warts) and types 16 and 18 (high-risk strains associated with 70 percent of cervical cancer). Do the numbers: the vaccine is not 100-percent effective. It casts a wide net, but some fish will swim through or over or around.
It’s also important to note that Gardasil is not a cure for cervical cancer or a pre-existing HPV infection (even if it happens to be type 6, 11, 16, or 18). It’s a preventive vaccine, not a therapeutic one. Preventive vaccines target “late proteins,” with which young viruses construct capsules around themselves prior to being jettisoned from their host cells.
Think of late proteins as the sport coat that a virus wears when it’s out looking for a new home. Preventive vaccines essentially provide the immune system with a description of this sport coat; then, should a viral intruder appear thusly appareled, it can be killed. Once a virus is able to slip inside a host cell, though, its fashion choices are invisible to the immune system, and the antibodies raised by the preventive vaccine are powerless to stop it.
Therapeutic vaccines, on the other hand, target “early proteins,” which show up like a “Do Not Disturb—Virus Replicating” sign on the surface of a cell when a virus is living inside it. If a person’s immune system has been tipped off by a therapeutic vaccine with a description of a specific virus’s early proteins, an infected host cell can be identified and then bombarded with antibodies and destroyed by white blood cells. If cervical cancer cells are producing some of these early proteins (as they often do), an immune system stimulated by a therapeutic vaccine would be able to destroy and eliminate these cells as well.
It’s worth repeating that Gardasil, as a preventive vaccine, does not function this way against existing infections or cancer. Nevertheless, its 100-percent effectiveness in preventing the HPV strains it does target is remarkable. If you think creating a vaccine is simple work, take a look at all the money and resources that have been committed to finding a vaccine against HIV, the virus that causes AIDS. “Tricky” doesn’t begin to describe it.
Which is a good reminder that Gardasil is no permission slip for promiscuity. It might protect a person from common strains of HPV, but not from HIV, herpes, chlamydia, gonorrhea, and other sexually transmitted diseases. Hooking up remains a dangerous game. As the National Cancer Institute states bluntly, “The surest way to eliminate risk for genital HPV infection is to refrain from any genital contact with another individual.”
And the surest way to avoid credit-card debt is to not own one. Or to have just one and use it wisely. MM
Craig Bowron is a Twin Cities internist.