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.
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 U.S. Centers for Disease Control and Prevention recommends that all 11- and 12-year-old boys and girls be vaccinated against HPV. Currently, two vaccines are available. Each requires three shots and each shot costs approximately $130, although actual out-of-pocket expenses depend on an individual’s health insurance plan. Some key differences exist between the two vaccines:
Gardasil (Human Papillomavirus Quadrivalent [Types 6, 11, 16, 18] Vaccine, Recombinant)
Manufactured by Merck & Co.
- Approved for males and females between ages 9 and 26
- Protects against HPV types 6, 11, 16 and 18.
- Approved for the prevention of anal cancer, cervical cancer, vaginal cancer, vulvar cancer, precancerous lesions in the genital area and genital warts.
Cervarix (Human Papillomavirus Bivalent [Types 16 and 18] Vaccine, Recombinant)
Manufactured by GlaxoSmithKline
- Approved for females between ages 9 and 25
- Protects against HPV types 16 and 18.
- Approved for the prevention of cervical cancer and precancerous cervical lesions.
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.
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.
According to the National Cancer Institute, there are more than 150 types of HPV, and at least 15 of them have been linked to cancer. Two types, HPV-16 and HPV-18, cause about 70 percent of the cervical cancers associated with HPV, according to a 2010 study from the
Lancet Oncology. Both the Cervarix and Gardasil vaccines offer protection against those two types, but about 30 percent of cervical cancers are caused by HPV types that aren’t covered by either vaccine. So getting vaccinated, doctors caution, doesn’t mean a woman can forgo routine Pap testing.
Someday, researchers hope, that might change. They are working to develop a vaccine that will protect against more types of the virus—and one that may potentially benefit people with an existing HPV infection. (The two existing vaccines do not help individuals who already have an infection.) “The second-generation vaccines will be designed to induce an immune response against a different part of HPV,” says Mark H. Einstein, a gynecologic oncologist at the Albert Einstein College of Medicine in New York City. “If successful, the result will be a vaccine that will potentially have a lot more cross protection than the current ones.”
But, Einstein stresses, parents shouldn’t wait for a new vaccine before getting their children vaccinated. It could be many years before a new one becomes available.
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. 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.
HPV can be spread from skin-to-skin contact of areas not covered by a condom, explains Lowy. And though there isn’t any concrete evidence of how oral HPV infections are contracted, Maura L. Gillison, a head and neck medical oncologist at the Ohio State University in Columbus, who led the recent
JAMA study, notes that some preliminary research has suggested that the virus may potentially be spread by mouth-to-mouth or hand-to-mouth contact.
Cervical cancer rates in the United States are relatively low: The National Cancer Institute estimates that in 2012 about 12,000 Americans will be diagnosed with cervical cancer and about 4,200 will die of the disease. These low incidence and death figures are due largely to the widespread availability since 1943 of the Pap test, which can detect precancerous cervical cells. Since the 1950s, the death rate in the U.S. has dropped by nearly 70 percent.
After a woman receives an abnormal Pap result, her health care provider can perform a biopsy and remove the abnormal tissue before it turns cancerous. But removing precancerous cells won’t stop future abnormalities from developing, and a woman with a persistent HPV infection may need many biopsies over the course of her life. That comes with certain risks. The procedures used to remove abnormal tissue can weaken the cervix, explains Mark H. Einstein, a gynecologic oncologist at the Albert Einstein College of Medicine in New York City, and a weak cervix increases a woman’s risk of pre-term birth.
It’s a fear that sticks with some patients. “Every time I have a procedure, in the back of my mind, I wonder, ‘Is this the one that’s going to keep me from being able to carry to term?’ ” says Allison Cunningham, a special education teacher from Westampton, N.J. Cunningham was 19 when she was diagnosed with HPV after an abnormal Pap. Now 29, she’s had six cervical biopsies. “There is a level of anxiety that goes with having HPV. I wish the vaccine was around when I was a teenager. I would have gotten vaccinated.”
Vaccination—Not Just for Girls?
The prevalence of HPV was part of the basis for a 2007 recommendation by the CDC’s Advisory Committee on Immunization Practices that all girls get vaccinated at age 11 or 12; the vaccine is most effective if given before a person becomes sexually active.
Despite the recommendation, Einstein says, some parents remain concerned that the vaccine might cause dangerous side effects. But, he says, ongoing research investigating the vaccine’s safety has found only minimal side effects, like temporary swelling or pain at the injection site, which are similar to side effects associated with other vaccinations.
“Some people may have a low-grade fever, and some adolescent girls have fainted within a few minutes of getting the vaccine,” adds Lowy. “But these are recognized side effects of most vaccines. Claims of other side effects have not been substantiated.”
Now the vaccine isn’t being endorsed only for girls. In October 2011, the CDC began to recommend that 11- and 12-year-old boys be vaccinated, in addition to girls. The Gardasil vaccine is approved to protect boys from genital warts and anal cancer, and vaccinating boys means that fewer of them will spread the virus to girls.
Vaccinating one segment of the population for the benefit of another isn’t new. “The rubella vaccine is given to boys and girls, but the purpose of rubella vaccination is to prevent fetal abnormalities in pregnant women,” explains Lowy. “So boys receive the vaccine for altruistic reasons. There is precedent for taking vaccines for the purpose of helping other people.”
The vaccine may have additional benefits. Beyond protecting girls and boys against genital warts and cervical or anal cancers, Lowy says, it’s theoretically possible that HPV vaccination imparts protection against other HPV-linked cancers—though there is currently no data to support such a claim. In particular, effectiveness of an HPV vaccine against oropharyngeal cancer would be hard to demonstrate, says Lowy, so it’s unlikely any vaccine will be approved for that use soon.
Cervical and anal cancers are preceded by precancerous lesions that are easy to identify and remove before they become cancer, he explains. When researchers conducted trials to prove the HPV vaccine prevented cervical and anal cancers, they used those precancerous lesions as indicators of the vaccine’s effectiveness. The vast majority of people who were given the vaccine did not develop such lesions. But precancerous lesions can’t be used as an indicator of effectiveness in oropharyngeal cancers, so researchers would need to conduct much longer trials and wait for trial participants to develop tumors, to demonstrate whether the vaccine offers any protection against them.
The human papillomavirus (HPV) was first linked to cervical cancer in 1983. Since then, scientists have discovered that the virus is responsible for a large proportion of several other types of cancer: anal, oropharyngeal, penile, vaginal and vulvar cancers.
As scientists continue to look at the HPV-cancer connection, they may find more. In 2010, an international team of researchers found a potential link between HPV and squamous cell skin cancer, and in 2009, a study reported in the journal
Lung Cancer found a possible connection between lung cancer and the virus.
Total diagnoses per year
in the U.S.
associated with HPV
“The vaccine isn’t given in the genital tract,” Lowy points out. “It is given systemically into the blood stream, so there is every reason to assume that the vaccine would work for other cancers. There’s just no data.”
When the HPV vaccines were first developed, there wasn’t as much evidence linking HPV to oropharyngeal cancer, adds Gillison. But she thinks that now that HPV has been shown to cause many of these cancers, there will be interest in studying whether the vaccine can prevent oral HPV infection. However, she cautions, further study is needed before the vaccine can be recommended or approved as a way to prevent any HPV-related oropharyngeal cancers.
“I would recommend the vaccine for boys based on the existing data for prevention of anal cancer and genital warts,” says Gillison. “I don’t think, as an evidence-based scientist, that I can say, ‘Vaccinate your sons to prevent oral cancer.’ I’d love someday to be able to say that. But sometimes we’re surprised. You can never be certain: Perhaps there’s something about the oral cavity that would make the vaccine not work there.”
Whether or not the vaccines prove to be effective against HPV in other parts of the body, existing evidence shows the vaccine is already something parents should consider—and discuss with their children’s doctors.
March 29, 2012