When actor Michael Douglas told a reporter that his throat cancer was caused by HPV contracted through oral sex, two themes emerged that had nothing to do with celebrity gossip. The first was incredulity - since when was oral sex related to throat cancer? Even the reporter thought he had misheard. The second was embarrassment. This was too much information, not only about sexual behavior but also about one's partners.
Douglas apologized, and maybe the world was not ready to hear the greater truth behind what he was suggesting.
That was four years ago.
Today, there is no doubt in the medical community that the increase in HPV-related cancers such as the one Douglas described - which he later explained was found at the base of his tongue - is caused by sexual practices, in his case cunnilingus. And there is an urgency to better treat and prevent what is becoming the one type of oral cancer whose numbers are climbing, especially among men in the prime of their lives who have decades to live with the consequences of their cancer treatment.
The number of people diagnosed with HPV-related oropharyngeal cancer, tumors found in the middle of the pharynx or throat including the back of the tongue, soft palate, sides of throat and tonsils - is relatively small - about 12,638 men and 3,100 women in the United States each year, according to the Centers for Disease Control and Prevention. But these numbers are expected to continue to rise, overtaking incidence of cervical cancer by 2020. One study revealed the presence of HPV in 20.9 percent of oropharyngeal tumors before 1990, compared with 65.4 percent in those sampled after 2000.
It's an alarming trend considering HPV, or human papillomavirus, is the most common sexually transmitted infection in the country. The CDC estimates that nearly all sexually active men and women will get a form of the virus at some point. Although most HPV infections go away on their own, they are causing 30,700 cancers in men and women every year, including cervical, vaginal and penile cancers along with oral cancers.
Health agencies are pushing hard for HPV vaccinations, which they say could prevent most of those cancers. The CDC says all 11- and 12-year-olds should be vaccinated. And last year, the Food and Drug Administration approved a new two-dose series for children ages 9 to 14. And the American Academy of Pediatrics recently updated its vaccine recommendations to reflect that two-dose schedule, a reduction from the three shots previously required. (Children over 14 still need three shots.) The hope is to increase rates of completed vaccinations, which have lagged in the decade since the vaccines were released, averaging 42 percent for girls and 28 percent for boys, far below the Healthy People 2020 goal of 80 percent.
The patients showing up in Ben Roman's office at Memorial Sloan Kettering Cancer Center in New York, where he works as a head and neck surgeon and health-services researcher, came of age not only before these vaccines hit the market, but also before HPV and its link to cancers was fully understood. These cases, experts say, probably reflect several separate but interconnected factors: the sexual revolutions of the 1920s and 1960s that introduced more HPV into the general population, the changing sexual practices of young people who report more histories of oral sex, and that it can take 10 to 30 years for tumors to develop after an infection.
Roman has seen an increase in a new type of head and neck cancer patient. They are typically white, middle-aged men, otherwise healthy, who have no history of smoking or drinking. They may have first noticed a mass in their necks or lymph nodes while buttoning a shirt or shaving. An ear, nose and throat doctor has determined the primary source of the cancer: the tonsils or base of the tongue.
"Most people are familiar with tonsils in the back of the throat," Maura Gillison, a leading expert in HPV-related cancers at the University of Texas MD Anderson Cancer Center, said. "But we also have them in the base of the tongue."
The palatine tonsils are on the sides of the throat, and there are also lingual tonsils on the back of the tongue. Both areas are made of the same lymphoid tissue at particular risk for HPV infection, and are part of what specialists call Waldeyer's Ring.
Experts are not sure why an HPV infection in the tonsils is more likely to lead to cancer. It could be because of their anatomy, which has crypts and crevices, making it harder to clear an infection. Gillison said it could also be because of where the tonsils are in the body, an area that serves as a transition from the outside to the inside, much like the genital tract and cervix.
German researcher Harald zur Hausen identified the types of HPV that cause cervical cancer 34 years ago, work that earned him the Nobel Prize in 2008 and contributed to the development of the HPV vaccine. One of those types, HPV-16, is identified in more than half of cancers in the oropharynx, according to the National Cancer Institute.
But there are important distinctions between men and women when it comes to HPV-related cancers. Cervical cancer deaths, for example, have been greatly reduced through early detection with the use of Pap smears. The same screening for precursor lesions or pre-cancer is not yet possible for the oropharyngeal cancers, commonly referred to as OPC or OSCC, for oropharyngeal squamous cell carcinomas.
The male risk
Another difference is how men and women respond to infection. The majority of women develop antibodies to clear HPV when exposed vaginally. These antibodies remain in the body so that a woman is protected from a subsequent oral infection. Men, in contrast, are much less likely to develop antibodies after genital exposure to the virus. When tested, their titers - a measurement of antibodies - are lower, leaving them five times more likely than women to have an oral infection.
HPV is considered an unusual virus because it does not travel through the bloodstream. Infection is localized, meaning it stays at the place where contact occurs. In tonsil cancer, then, oral sex becomes a relevant risk factor, so significant that in an article in the Journal of Clinical Oncology, Gillison and her colleagues stated that the number of these oral sex partners in a lifetime is the behavior measure that is, ". . . most strongly, consistently, and specifically associated with OPC (tonsil and base of tongue)."
Treating a cancer related to a sexually transmitted infection brings up sensitive questions. Roman said a patient's spouse will often pull him aside to ask: "When did he get this? Was he cheating?" He suggests the patient was probably exposed years ago. But from the viewpoint of prognosis, the HPV-related cancers respond better to treatment.
That fact has prompted rapid changes in treatment protocols that were as recently as five years ago based on heavy smoking and drinking. These new strategies back down from the aggressive radiation, chemotherapy and surgery that exposed patients to high toxicity and could damage the ability to speak and swallow.
When Gillison started her research in 2000, there was little awareness that sexual behavior contributed to cancer of the throat, and fellow researchers were skeptical.
"People were laughing. They thought it was absurd," she said. Now, Gillison is credited with formally putting together the behavioral data and biomarkers to quell any skepticism, Carole Fakhry, an associate professor of otolaryngology and surgeon at Johns Hopkins, said.
Others had noted HPV in oral cavity cancer, but no one was sure whether it was a fluke or more significant. So Gillison reviewed tumor specimens collected by a colleague and then set out to study all of the available literature, presenting an analysis in 2009 that compared the survival rates of those with HPV-positive and -negative oropharynx cancers. Gillison describes her work - a confluence of observations in the lab and clinic - as an act of serendipity.
"I have always been interested in the association between infectious diseases and tumors because there are so many opportunities to intervene. If an infection causes a cancer, you can try to prevent infection in the first place, or screen, or if it's developed you can use the fact that it's associated with a virus - you can treat cancer by treating infection."
As far as vaccination's effect on preventing OPC in men, data is still under review. Officially, the vaccine is recommended for boys and young men to prevent genital warts and anal pre-cancers. But those focused on pediatrics, such as Margaret Stager, director of adolescent medicine at MetroHealth medical center in Ohio and an official spokeswoman for the American Academy of Pediatrics, say that HPV vaccination clearly decreases spreading of HPV through the community, offering immediate, midrange and long-term benefits. And the current vaccines do protect against HPV-16, one of the high-risk types of the virus found in both cervical cancer and a majority of OPC.
New, easier vaccine
The new two-dose vaccination is designed to reach children when their antibody response is highest and make completion less cumbersome, as are electronic medical records that cue physicians when a vaccine is due. The District of Columbia is one of the few areas that has made the vaccine a required immunization for students in grades six through 12, although families may opt out.
There is still a gap in knowledge among some general practitioners and dentists, according to Gillison.
It is not uncommon for her to hear a story from a patient who comes to her after six months or so after going to his doctor.
"He told me not to worry because I was fighting off an infection. He gave me antibiotics. They were not working. Then another lump occurred next to that one . . . "
The patient is young, healthy and doesn't smoke. He has a sore throat and a neck mass that doesn't respond to antibiotics.
Those in the front lines of medical practice, she said, should have in mind the question: Could this patient have head and neck cancer?