The ABCs of HPV
Most people know that human papillomavirus (HPV) causes cervical cancer. But HPV is also behind other types of the disease, including cancers of the vulva, penis, and anus. One type has surpassed even cervical cancer as the most common: HPV-associated cancer of the oropharynx, or throat.
“The vast majority of people have no idea that HPV causes this subset of cancers,” says Daniel Faden, MD, a head and neck cancer surgeon at Massachusetts Eye and Ear. Even some doctors don’t realize it, he says.
“If you look at the trends, cervical cancer rates continue to go down due to effective screening,” Faden adds. “Oropharyngeal cancers, on the other hand, are rising at epidemic proportions.”
HPV-related oropharyngeal cancers occur in a specific area of the throat: in the tonsils and at the base of the tongue, the part people can’t see or touch. They are a subset of squamous cell carcinoma, the most common form of cancer in the head and neck, says Jennifer Cracchiolo, MD, a head and neck cancer surgeon at Memorial Sloan Kettering Cancer Center. The most common risk factor for these cancers used to be alcohol and tobacco use, but now 70% to 90% are caused by HPV.
According to the CDC, between 1999 and 2015, cervical cancer rates decreased 1.6% per year, but oropharyngeal cancer rates rose 2.7% per year among men and 0.8% per year among women. These cancers are also increasingly diagnosed in younger people, many in their forties or fifties.
Current data shows that the HPV vaccine has led to a significant decrease in the number of young women with HPV and HPV-associated cervical precancers, including unvaccinated women who likely benefit from herd immunity. It’s projected that the vaccine will lead to a similar reduction in oropharyngeal cancers. But the vaccine is just over a decade old. Since most people are diagnosed with oropharyngeal cancer in their 50s or later, people at risk of developing these cancers in the near future have likely not been vaccinated.
Because it is most effective when administered before a person becomes sexually active, the U.S. Food and Drug Administration (FDA) recommends routine vaccination for 11- and 12-year-olds. First approved for girls in 2006, the HPV vaccine was not technically greenlit for boys until 2014, when the FDA gave the go-ahead to Gardasil 9, the version in use now. In late 2018, the FDA recommended that most previously unvaccinated people up to age 26 be vaccinated, and the agency approved the vaccine for use in people up to age 45.
So, if you’re between 27 and 45, should you get vaccinated?
It certainly can’t hurt — the vaccine is very safe and side effects are mild — but it probably won’t prevent cancer. “We know that 80% of HPV infections are acquired before age 26,” says Dr. Rebecca Perkins, an HPV researcher and OB-GYN at Boston Medical Center. “If you’re 27 to 45 and you’re going to get cancer, you are probably already infected with that HPV type.”
Perkins says that in the clinical trials that tested the vaccine up to age 45, the researchers limited the trial to women who had on average only one sexual partner, and no more than four. “The vast majority of the adult population would not have qualified,” she says.
“HPV-related oral cancers are increasing, and that is going to continue until we do something to change it.”
Faden explains that HPV-associated cancers are typically diagnosed about 20 to 30 years after HPV infection, meaning that people contract the virus in their twenties and thirties and then present with cancer around their fifties. While he wouldn’t routinely recommend the vaccine to adults, he says it could be appropriate in some cases. “If someone is in a monogamous relationship, if they’re going to get HPV from that partner, they already have. But say someone was married, got divorced, and is re-entering the dating pool, where they could be exposed to new infections. In that case it makes sense to vaccinate,” says Faden.
Another consideration: If you are 26 or under, your health insurance should cover the vaccine as preventive care, but if you are 27 or over you could end up paying for it out of pocket. When it comes to cervical cancer, says Perkins, there’s no substitute for regular screening, which greatly reduces death from the disease. Unfortunately, the same cannot be said for throat cancers.
When someone has an abnormal Pap smear, explains Perkins, most often what’s detected is an active HPV infection that’s causing minor changes to cervical cells. The immune system will combat and clear up HPV, and these changes will go away on their own about 70% of the time. Pap tests can also detect more significant cervical changes that are considered precancerous, allowing for appropriate treatment before cancer develops.
Unfortunately, the same can’t be said for throat cancer. “We currently have no screening protocols to catch early-stage oropharyngeal cancers,” says Faden. “We do not think there is a premalignant state like with cervical cancer, so there’s no way to screen for it.”
The location of oropharyngeal tumors also makes them hard to detect. In the cervix, there’s one area called the transformation zone where cancer almost always starts. “You can see it,” says Perkins. Oropharyngeal tumors, on the other hand, are usually small initially and deep in the throat.
Because these cancers have often metastasized before they are detected (meaning the cancer has spread beyond the initial infection area), one of the most common symptoms is a swollen lymph node that stays that way. It’s normal for lymph nodes to swell after an infection, but if the swelling doesn’t resolve within a few weeks — or there’s persistent throat pain — it should be checked out by a doctor.
“What I really want to get out to the medical community is that if a patient comes in and says, ‘I was shaving, I noticed this neck mass, it’s new,’ or ‘I don’t know how long it’s been there,’ they should be considered for a biopsy,” says Cracchiolo.
In terms of prevention, it’s key to remember that HPV is sexually transmitted. “We know that an HPV-related cancer is closely tied to a person’s number of oral sex partners,” says Faden. “I’m not in any way implying that people should modify their sexual practices, but they should engage in safe sex practices.”
While HPV-associated oropharyngeal cancers are on the rise, they still affect a small portion of the population. According to Faden, studies have found that at any given time, about 67% of adults have HPV in their oral cavity. About 1% of those people have HPV-16, the strain most associated with cancer. However, only a small portion of that 1% will go on to develop cancer. The CDC attributes just under 13,000 new cases of oropharyngeal cancer to HPV infections each year.
This is because almost all cases of HPV resolve on their own. Only a very small percentage of people develop the type of persistent HPV infection that leads to cancer. Little is known about why some people develop these persistent infections and others do not, but it’s an area of active research.
Another comforting fact is that HPV-associated oropharyngeal cancers are highly treatable. “In contrast to about 50% to 60% survival in cancers attributed to smoking and drinking, it’s 85% survival within 5 years. So it’s a very curable cancer,” says Cracchiolo.
The Sloan Kettering surgeon is focused on developing treatments for HPV-associated throat cancer that will have fewer long-term effects on patients, given the high survival rates and relatively young age of diagnosis. “With very curable cancers, we’re often looking to de-escalate treatment,” she says. “Treatment in these cases can involve chemo, radiation, surgery, and combinations of those things. So we are looking at how we can decrease intensity and reduce long-term toxicity while maintaining cure rates.”
Experts say parents and doctors should continue to strongly encourage early HPV vaccination. Vaccinating all adolescents has the potential to prevent 25,000 HPV-related cancers per year, whereas vaccinating all adults would prevent only 193 cancers per year, according to experts.
“HPV-related oral cancers are increasing, and that is going to continue until we do something to change it,” says Faden, adding that, because there’s up to a 30-year lag between infection and cancer, the effects of vaccination won’t be visible for several years. “In my [own] practice as a physician I may not even see it. It’s going to be the next generation.”