discoveries magazine

An Epidemic Ignites

The usually harmless sexually transmitted human papillomavirus (HPV) is triggering a surge of throat cancer among Baby Boomers. The sexual revolution that liberated a generation also escalated their exposure to the virus. Two Cedars-Sinai investigators are working to ease the burden of treatment on the population most at risk—older men.

An illustration of a middle-aged man who's throat feels like it's on fire, an early symptom of throat cancer after being exposed to HPV.

Yuko Shimizu

"Where did it come from?" Bill Reid asked. 

"It makes no difference," his wife Ruth replied. His question wasn’t about his newly diagnosed throat cancer. It was about what caused it: the sexually transmitted human papillomavirus (HPV).

At age 76, Bill Reid had been feeling fine, except for a bit of discomfort in his throat that he thought was postnasal drip. Then, in early 2016, a routine check-up resulted in the throat cancer diagnosis. Reid was still absorbing this shocking news when he asked the question about HPV.

His doctors at Cedars-Sinai explained that 70% of throat cancers are caused by HPV, and the virus is so prevalent that no one can trace its origin. 

HPV is like the common cold: easy to catch and usually harmless and fleeting. But high-risk strains of the virus can linger undetected for many years and then trigger a potentially life-threatening health crisis. 

HPV-related throat cancer is increasingly prevalent among men like Reid. His care team at Cedars-Sinai was led by two clinical scientists who share a deep concern about the growing impact of HPV-related throat cancer on his generation. 

For years, this cancer was associated almost exclusively with relatively young, healthy patients. Allen Ho, MD, director of the Head and Neck Cancer Program in Cedars-Sinai’s Samuel Oschin Comprehensive Cancer Institute, and Zachary Zumsteg, MD, assistant professor of Radiation Oncology, were among the first to document a sharp increase in HPV-positive oropharyngeal squamous cell cancer—which affects the back of the throat, base of the tongue and tonsils—among persons over age 65. The increase appeared to be driven predominantly by cancers in white men, although it was observed to a lesser degree in other demographics as well. Scientists predict that incidence of the disease will continue to rise dramatically in this group for at least the next decade. 

As Baby Boomers age, investigators are concerned that this cancer could take a heavy toll on quality of life at a time when patients may already be grappling with multiple health issues and increasing frailty.

Love on Independence Day

On July 4, 1989, Reid, then a California resident traveling on business, looked up from a Robert Ludlam novel in an airport boarding area and saw a woman who was "very attractive in a non-flashy sort of way." Their eyes met. After they landed in Florida, he approached her in baggage claim. Bill and Ruth Reid had their first date that night. Eight months later, after a whirlwind long-distance courtship, they were married and began their life together in Florida. 

Like most couples, they had no specific idea what "in sickness and in health" might mean for them. But they never doubted they would be there for each other in a crisis.

After his diagnosis, Reid's wife, a retired surgical nurse, reassured him: "Whatever caused this cancer makes no difference at all. As far as I'm concerned, you breathed the wrong air one day. It's not like HPV is out there with a little red tag on it, and you can put a mask on and avoid it."

Ruth and Bill Reid sitting together on a couch while Ruth kisses her husband Bill on the cheek after being diagnosed free of throat cancer from HPV.

Ruth Reid lands a kiss on husband Bill at Europa Village winery in Temecula, where they are wine ambassadors. Bill can no longer taste his favorite varietal since receiving treatment for throat cancer, but the devoted couple is thrilled he is cancer-free.

Destigmatizing HPV

When Ho gives a diagnosis related to HPV, he offers information that he hopes will spare patients and their partners from going down a rabbit hole of questions related to sexual history. "The virus is pretty much everywhere. Eighty percent of people who are sexually active get the infection at some point in their life," he says.

Nearly 80 million Americans currently have one of the many types of HPV, according to the Centers for Disease Control and Prevention (CDC). In 9 out of 10 cases, the immune system fights it off within a couple of years with no symptoms—though low-risk HPV strains can cause genital warts. But high-risk HPV causes the majority of cancers of the cervix, vagina, vulva, penis, anus and throat. While Pap smear tests help identify women at risk for cervical cancer early, no screening test is available for any of the other HPV-related cancers.

Ho and Zumsteg assure patients there’s no way to know how they got HPV or how long they’ve had it. It can be decades before cancer develops, so some carry the risk with them into old age. 

"We do a lot of destigmatizing," Ho says. "This is something patients have no control over. It just happens. Some patients feel ashamed or embarrassed, but they shouldn’t."

The rate of HPV-related throat cancer is significantly higher among men than women. The same is true for the rate of oral HPV infection. At any given time, 10% of men have oral HPV versus 3.6% of women, according to the CDC. Women may have a stronger immune response to the virus than men. 

"It could be biological or behavioral. We don’t know,” Ho says. “But we do know that certain sexual practices increase the risk for this cancer."

Changing Sexual Mores

Zumsteg co-authored a paper published in June 2019 in the Journal of Clinical Oncology that showed the sharp increase in HPV-related throat cancer among older men reflected a growing risk to those born between 1940 and 1960. The study suggested that this was likely due to changes in sexual behaviors during the 1960s and beyond, as practices that increase exposure to HPV—including multiple partners, earlier sexual activity and oral sex—became more prevalent.

The HPV virus can be transmitted through any type of sexual, skin-to-skin contact, including deep kissing, notes Bobbie J. Rimel, MD, assistant professor of Obstetrics and Gynecology at Cedars-Sinai. She explains that the virus is passed between mucous membranes like the common cold. Just as some people develop pneumonia from a cold, some develop cancer from HPV. Smoking and alcohol can increase the risk that HPV will cause cancer, according to the CDC. 

Scientists have provided an effective solution—the HPV vaccine. But not enough young people are getting vaccinated. Rimel believes a realistic view of sexual behavior in today’s world is needed to increase the vaccination rate. 

"We've moved on from the preconceived notions of sex that our grandparents had," she says. "The norm today includes a wide variety of sexual practices, and we must take into account the risks that come with this. Part of the sexual revolution was a sexual evolution, and we have to go with that in science, too. Thank God we have scientists who developed a vaccine that can protect our children and grandchildren from HPV-related cancers."

The Reids set aside the topic of HPV to focus on "getting rid of cancer," but they knew they would come back to it later—not to discuss the past but to advocate that boys and girls get the HPV vaccine, along with adults up to age 45.

The Reids bring this topic into the conversation as often as possible. As wine "ambassadors" at a vineyard near their home in Temecula, California, the couple is as likely to recommend the vaccine as they are to sing the praises of local wines. 

“We're very open about the cause of Bill’s cancer, and we tell people if he'd had the opportunity to have the vaccine, this probably wouldn’t have happened to him," Ruth Reid says.

'You Can Do It'

It was not unusual that Reid's cancer had progressed so dangerously without notice, as throat cancer is hard to detect in early stages. One of its most common signs is a lump in the throat men find while shaving.  

Reid faced a grueling regimen of chemotherapy and radiation five days a week for seven weeks. He lost 50 pounds at an alarming rate. "My throat hurt so bad, even with all the pain medication, that I could barely swallow," he says. “I had no taste even for the liquids I lived on for three weeks. I had absolutely no energy. I would fall asleep at the dinner table."

During the final two weeks of treatment, Reid was so weak that he trailed behind his wife as they headed to radiation oncology treatment.

"I traveled a lot for years and I used to zoom through airports. Ruth would say, 'Slow down. Let me catch up with you.' Now she had to slow down for me," he explains. "I was cold, tired and dehydrated. I was pretty low." 

Zumsteg says side effects tend to build up during radiation treatment "and then gradually get better in a mirror-image fashion." However, some patients have long-term difficulties with dry mouth, swallowing, sense of taste and smell, and overall energy. 

Reid is no longer able to enjoy a good Syrah or even smell a skunk, but he looks robust after regaining 30 pounds and is back to the activities he took up after retiring from a long career as a cartographer—including exercising several days a week and tending his vegetable garden. Most important, he says, is that he remains cancer free. He still comes to Cedars-Sinai for checkups and receives physical therapy for lymphedema—swelling in the neck that can be a side effect of radiation.

Less May Be More

With patients like Reid in mind, Ho and Zumsteg are working to determine whether less is more in treating HPV-related throat cancer. Ho has been reevaluating how the stage of the disease is determined to help ensure that each patient receives the right level of treatment. And Zumsteg is designing a clinical trial to explore whether radiation treatments can be "de-intensified" to reduce side effects. 

"We have to figure out how to treat older patients in the best way possible because we’re seeing more and more of them," Zumsteg says. "Patients over 70 have either been excluded from clinical trials or enrolled in very small numbers. These are the most challenging people to treat, yet we have virtually no data to tell us whether the things we do for a 50-year-old with this cancer are also beneficial for someone 75 or 80."

Both Ho and Zumsteg are optimistic about reducing the burden of treatment on older patients because HPV-related throat cancer is more responsive to treatment than the now less common type caused by smoking. 

While Ho and Zumsteg look toward the future, Reid savors each moment and jumps at opportunities to encourage other patients with the words that helped him most: "You can do it."

"I always prayed for knowledge and wisdom for the doctors—that they would know what could be done and pick the right things to do for me," he adds. "Looks like they did."

A Cancer on the Rise and an Underused Vaccine
  • Throat cancer has surpassed cervical cancer as the most common HPV-related cancer in the United States, according to the National Cancer Institute.
  • Driven by HPV, the incidence of throat cancer among white men over 65 is rising while the rate of smoking-related head and neck cancers is declining.
  • Researchers predict that incidence of HPV-related throat cancer will increase dramatically between 2016 and 2029: from 40.7 to 71.2 per 100,000 in white men aged 65–74 and from 25.7 to 50.1 per 100,000 for those aged 75–84. 

An estimated 34,800 new cancer cases are linked to the human papillomavirus (HPV) in the U.S. each year. A vaccine that protects against the strains of HPV most likely to cause cancer could virtually eliminate this statistic. 

“It’s going to take many years, but the closer we get to a 100% vaccination rate for both girls and boys, the closer we will be to eradicating HPV as a cancer-causing virus,” says Bobbie J. Rimel, MD, assistant professor of Obstetrics and Gynecology at Cedars-Sinai.

The vaccine is most effective when given before exposure to HPV through sexual activity and while the immune system is strongest. The Centers for Disease Control and Prevention (CDC) recommends all girls and boys get two doses of the vaccine at ages 11 or 12, but reports that only about 49% of teens are up-to-date on the HPV vaccine.

“Some parents are afraid the vaccine will be a license to have sex,” Rimel says. “They want to assume their children won’t have sex before marriage and won’t have multiple partners, but the data doesn’t support that,” she says. (According to the 2017 National Youth Risk Behavior Survey, 40% of high school students are sexually active.)

The CDC also recommends the vaccine for females up to age 26 who were not previously vaccinated and for males up to age 21, particularly if they have sex with men or have a compromised immune system. And the Food and Drug Administration has approved the vaccine for men and women up to age 45. Older people may benefit because even those who have some type of HPV may not have been exposed to one of the cancer-causing strains covered by the vaccine.