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The HPV Cancer Connection: Take 2

New insights about HPV’s role in multiple cancers are rapidly expanding—as are thoughts about who should be vaccinated against the virus, and why. By Alanna Kennedy-Gorman

You've likely had a human papillomavirus (HPV) infection—you may have even had several and never known it. That's because many types of this virus—which has long been linked to cervical cancer and genital warts—have no symptoms and are quickly cleared by the human immune system. And so, despite its prevalence, until a few years ago, few people had even heard of HPV. 

HPV Vaccines: The next generation
Could a more protective vaccine be
on the way?

HPV Prevention: What vaccines are available?
Current vaccines on the market offer
different protection.

Cancers Linked to HPV
Scientists have discovered that the virus
is responsible for several types of cancer.

If Pap Tests Prevent Cervical Cancer,
Why Vaccinate Your Daughter?​

The removal of precancerous tissue
following an abnormal Pap may have
side effects.
That all changed in 2006, when the U.S. Food and Drug Administration (FDA) gave the green light to Merck’s Gardasil, the first vaccine approved to protect against two types of the virus known to cause the majority of cervical cancers. Soon, TV viewers were exhorted to “be one less” woman affected by the cancer. Three years later, GlaxoSmithKline’s HPV vaccine, Cervarix, hit the market.

Today, information (and misinformation) about HPV may seem nearly as prevalent as the disease itself. HPV is on TV, on posters at the pediatrician’s and gynecologist’s office, in the newspaper, and in presidential debates. But the conversation is no longer just about women, or just about cervical cancer. Researchers have found compelling evidence linking HPV to other cancers, including cancers of the oropharynx, which includes parts of the throat, tongue and mouth. (It’s a type of head and neck cancer that is dramatically on the rise.) And just last fall, the U.S. Centers for Disease Control and Prevention (CDC) expanded its guidelines to recommend that boys, not just girls, be vaccinated against the virus as part of their routine immunizations. 

The HPV-Cancer Link
HPV infects the epithelial cells that make up the skin and the lining of major cavities in the body, and it is the most common sexually transmitted infection in the United States, according to the CDC. At any one time, some 20 million Americans are infected with the virus, and at least half of sexually active men and women in the U.S. will have an HPV infection in their lifetimes. Even so, the biggest misconception about HPV is that infections caused by the virus aren’t common, says Mark H. Einstein, a gynecologic oncologist at the Albert Einstein College of Medicine in New York City. 

“People think of it like gonorrhea or chlamydia and other sexually transmitted diseases, where you’re likely to develop symptoms soon after exposure,” says Einstein. But, unless the virus causes genital warts or precancerous lesions, HPV doesn’t have symptoms. Because the CDC estimates that 90 percent of HPV infections clear up on their own within two years, most people who are infected never know it.

It’s when HPV doesn’t clear up that it can cause precancerous lesions on the cervix or genitals, which in turn can lead to cancer, explains Douglas Lowy, a physician and cancer researcher at the National Cancer Institute (NCI). Of more than 150 types of HPV, 
15 have so far been linked to cancer. Many types of HPV can also cause genital warts, with 90 percent of warts linked to two types: HPV-6 and HPV-11.

At any time, 20 million Americans are infected with HPV, and at least half of sexually active men and women will have an HPV infection in their lifetimes. ​
HPV is perhaps most closely associated with cervical cancer. Cervical cancer rates in the United States have plummeted since the Pap test was developed in the 1940s. But even though regular Pap screening has reduced the cancer’s incidence, about 12,000 American women will be diagnosed with the disease and about 4,200 will die of it this year. 

Virtually all cases of cervical cancer are caused by HPV (70 percent of them by HPV-16 and HPV-18), suggesting that widespread vaccination against these types of HPV could reduce cervical cancer rates even further—especially in low-resource countries where Pap screening is uncommon, according to the World Health Organization. And doctors point out that cancer and genital warts aren’t the only consequences of HPV infection: Even if a woman gets regular Pap tests and abnormalities are detected before they become cancer, multiple procedures to remove irregular tissue can weaken her cervix. (See “If Pap Tests Prevent Cervical Cancer, Why Vaccinate Your Daughter?)

Nearly all HPV-linked cancers are related to the genitals: cervical cancer, anal cancer, penile cancer and vulvar cancer. But the virus has also been linked to some oropharyngeal cancers and possibly to some lung and skin cancers. (See “Cancers Linked to HPV.”) Interest in HPV’s role in oropharyngeal cancers is particularly strong. On Nov. 10, 2011, a team of researchers reported in the Journal of Clinical Oncology that the incidence of oropharyngeal tumors testing positive for HPV had increased dramatically since the 1980s. Between 1980 and 1984, about 16 percent of oropharyngeal tumors were HPV-positive. Between 2000 and 2004, 72 percent of tumors were HPV-positive. “The incidence of HPV-positive 
oropharyngeal cancer has been going up for about the last 20 years,” says Lowy. “And it’s the No. 2 HPV-associated cancer in the United States.”

Not only has the rate of HPV-positive oropharyngeal cancers risen, but a study published in 2008 in the Journal of Clinical Oncology found that people tend to be diagnosed with HPV-positive tumors at a younger age than individuals diagnosed with HPV-negative tumors. Other research has found that patients with HPV-positive tumors may respond better to radiation than patients with HPV-negative tumors, for reasons that remain unclear.

Although it’s not yet known what has caused the rise in rates of HPV-positive oropharyngeal cancer, researchers who published the 2008 data have suggested shifts in sexual behavior as a possible cause. More recently, data from a study published in the Feb. 15, 2012, Journal of the American Medical Association (JAMA) found that 6.9 percent of men and women 14 to 69 had an oral HPV infection, with infection much more common among men. Oral HPV infections among sexually inexperienced individuals were uncommon, and the prevalence increased with the number of recent or lifetime sexual partners. Among study participants who had more than 20 lifetime sexual partners, 20 percent had an oral HPV infection.

Although proper condom use can reduce the transmission of HPV from person to person, it isn’t 100 percent effective. In fact, many people just don’t realize how easily HPV can spread, says Einstein.

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