Slowing the Rise of Oropharyngeal Cancers

With the availability of a simple and safe vaccine with proven efficacy to prevent cervical and, it is widely thought, human papillomavirus-related oropharyngeal cancers, why aren’t more people demanding it and more providers recommending it? This question takes on new importance in light of the results of a recent national survey that concluded that the rates of adolescents receiving the HPV vaccine remain low since its initial approval for girls in 2006 and for boys in 2011 for prevention of HPV-related cancers.

Data from the National Immunization Survey-Teen (NIS-Teen) found that only 32 percent of girls between the ages of 13 and 17 have completed the recommended three-dose HPV vaccine, and only 49 percent of girls received at least one dose of the vaccine. For boys, the uptake was substantially lower, with only 8.3 percent of boys receiving at least one dose and no available data on those receiving the full three doses (MMWR Morb Mortal Wkly Rep. 2012;61:671-677). For older girls and women the uptake is also low, with data from a 2010 National Health Interview Survey showing that only one in eight women aged 18 to 26 years completed the three-dose regimen (Cancer. 2013;119:1386-1392).

The importance of increasing the uptake of HPV vaccination is highlighted by recent data that show its robust efficacy. Data published this spring showed that the vaccine decreased the rates of infection with HPV strains covered by the vaccine by 56 percent in 14- to 19-year old girls in the first four years following the vaccine’s availability, when compared with the four years prior to the vaccine’s availability (J Infect Dis. 2013; doi: 10.1093/infdis/jit192). Decreasing HPV infection through vaccination is considered critical to the reduction and prevention of specific cancers, with HPV infection considered the cause of most, if not all, cervical cancers, 90 percent of anal cancers, and 40 percent of vaginal, vulvar and penile cancers. In addition, HPV infection is reported to be linked to more than 50 percent of oropharyngeal cancers (J Natl Cancer Inst. 2013;105:175-201).

“The wonderful thing about these HPV vaccines is that when people are vaccinated before [they are] exposed [to the virus], they get a very robust immune response to the vaccine, and it is very protective against cervical and anal cancers,” said Gypsyamber D’Souza, PhD, associate professor at Johns Hopkins Bloomberg School of Public Health in Baltimore, who added, “We are hopeful that the vaccine is also protective against oropharyngeal cancers, since these cancers are caused by the same HPV types.”

HPV Vaccine and Oropharyngeal Cancers

The prevention of oropharyngeal cancers is a growing need given a dramatic increase in the incidence of these cancers over the past 20 years. A study published in 2011 showed a 225 percent increase in the incidence of oropharyngeal cancers from 1988 to 2004, and 90 to 95 percent of these cancers are due to HPV infection with the serotype strain 16 (J Clin Oncol. 2011;29:4294-4301).

Although current FDA recommendations do not include the use of the HPV vaccine to prevent oropharyngeal cancers, it is widely believed that the vaccine would be effective in preventing HPV-related oropharyngeal cancers. The lack of FDA recommendation for this indication is due to the difficulty involved in proving the efficacy of the vaccine for these cancers.

According to Erich Sturgis, MD, MPH, professor in the departments of head and neck surgery and epidemiology at The University of Texas MD Anderson Cancer Center in Houston, it will be extremely difficult to prove that the HPV vaccine is effective in preventing oropharyngeal cancers. Unlike cervical cancer, for which the development of premalignant lesions is evident in abnormal PAP smears many years prior to the development of invasive cancer, there is no good way to detect similar precancerous changes in the oropharynx. Although some have suggested testing for HPV DNA by swabbing the throat, Dr. Sturgis recommended against this. “The problem is that even if you find HPV DNA in the throat, that doesn’t mean that cancer will develop, and thus there is no clear screening or prevention available,” he said, adding that HPV DNA can be detected in 5 to 10 percent of people at any given time. He echoed a common assumption that the viral oncogenic process in the oropharynx is basically the same as in the cervix, and it is therefore expected that the vaccine will prevent oropharyngeal cancers as effectively as it does cervical.

Evidence of the possible efficacy of the HPV vaccine in preventing orophyaryngeal cancer is suggested by data from a randomized clinical trial of its efficacy in the prevention of cervical cancer, according to Dr. D’Souza. “What we see in preliminary data from the existing HPV vaccine trials is that none of the women randomized to receive the HPV vaccine developed oral HPV 16/18 infection, whereas some women who did not receive the HPV vaccine did develop those infections,” she said.

Because oropharyngeal cancers disproportionately affect men, Dr. Sturgis said that he would particularly like to see an increase in the number of boys who get vaccinated, stating that the current recommendation for boys is less rigorous than he would like.

Why the Low Uptake of the Vaccine?

According to Abbey B. Berenson, MD, MMS, PhD, director of the division of pediatric and adolescent gynecology at University of Texas Medical Branch in Galveston and author of the 2010 National Health Interview Survey article, the main barriers to the uptake of the HPV vaccine cited in the literature are:

• Cost;
• Lack of knowledge of and poor attitude toward the vaccine; and
• Inability to take time off of work to see a doctor.

Another study drilled these factors down a bit. The lead author of this study, Rebecca Perkins, MD, assistant professor in the department of obstetrics and gynecology, Boston University Medical Center, Boston, said that provider recommendation of the vaccine seems to be the most important factor for all adolescents regardless of race, ethnicity and income (Hum Vaccin Immunother. 2013 Apr 9;9). The study also highlighted the influence of parental attitude toward vaccines in general and toward the HPV vaccine in particular.

Parental beliefs and awareness of the HPV vaccine, said Dr. D’Souza, are the strongest predictors of the vaccine uptake. She cited the high interest in and uptake of the vaccine in other countries that administer the vaccine routinely in schools via an opt-out system, so that most adolescents receive it by default. “In the U.S., we don’t have a standardized way of delivering it, and we depend on families to ask for it and pediatricians to recommend it,” she said, adding that the problem for some parents is that they focus more on the vaccine’s association with sex rather than on its potential to prevent cancer.

One well-publicized reason has been the reluctance of some parents to provide a vaccine for a sexually transmitted disease because of fears that it may send children the message that they are condoning or encouraging sexual promiscuity.

Christine G. Gourin, MD, MPH, associate professor of the department of otolaryngology–head and neck surgery and director of the clinical research program in head and neck cancer at Johns Hopkins University in Baltimore, believes this type of stigma is dangerous. “The fact is that HPV infection is widespread, with up to 90 percent of adults contracting an infection at some point in their lives,” she said, particularly emphasizing the importance of the vaccine for prevention of oropharyngeal cancers because of the lack of good methods for early detection and screening for these types of cancers. Dr. Gourin emphasized both the reduction in mortality rates and the prevention of the significant disability these cancer patients suffer. “Because patients who develop these cancers are often younger than the typical head and neck cancer patient, they have many years ahead of them to live with the disability and sequelae of treatment, including disfigurement, trouble swallowing and radiation side effects,” she said.

How Otolaryngologists Can Improve Vaccination Rates

Dr. Sturgis emphasized the need to recognize the new profile of patients who present with oropharyngeal cancers. “Unlike the traditional profile of older men with a history of drinking and smoking, oropharyngeal cancers as related to HPV occur in men with a median age of 50 to 55 years, who have not smoked or with only a minimal smoking history, who often do not have an obvious lesion but show up with a lump in the neck, and often are of a higher socioeconomic status,” he said.

He emphasized the need for otolaryngologists to understand that the vaccine works best when administered in adolescence prior to exposure. Vaccinating someone at, for example, 30 or 35 may not prevent them from getting a cancer at 45 because they may already have been exposed. As many otolaryngologists see only older patients, one question that arises is whether adults should be vaccinated. “If an adult comes to me and wants the vaccine, what I say to the patient is that you have likely already been exposed to HPV, and we have no certain confidence that the vaccine will protect you now,” said Dr. Sturgis. However, he emphasized that because of the high safety of the vaccine, he doesn’t see a risk in adults receiving it, other than the fact that insurance may not cover it.

For Dr. Perkins, communication between providers and patients is the key that drives vaccination. “I think that otolaryngologists can help inform their patients about the link between HPV and oropharyngeal cancers and [explain] that vaccination should prevent many of them,” she said. “As a gynecologist, I do this when I am treating adult women for abnormal Pap smears. I tell them that we didn’t have a vaccine to prevent HPV when they were young, but we do now, and they can help prevent the disease in their daughters through vaccination.”

Dr. D’Souza also emphasized the need for good communication and, in particular, the need for otolaryngologists to tell patients that oral HPV infection is somewhat common and does not indicate promiscuity. “It only takes one partner to get a sexually transmitted disease,” she said. She also emphasized that the vaccine works equally well in girls and boys. For boys, she said that the key is that they are getting vaccinated for their own protection against penile warts, anal cancer and, hopefully, for oropharyngeal cancer as well and not just to protect future female partners from exposure to cervical HPV infection.

To help physicians talk to their patients, Dr. D’Souza and her colleague Carole Fakhry, MD, assistant professor of otolaryngology-head and neck surgery at Johns Hopkins, have developed a pamphlet that contains questions and answers on common behavioral issues and will be published in an upcoming volume of the Oral Oncology journal.