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A major study of oral infection with human papillomavirus (HPV) — now known to cause of a subset of oropharyngeal cancer — has found a much higher incidence in men than in women and has established sexual transmission as the main way it spreads. It also raises questions about whether existing HPV vaccines offer protection.
There is a rising incidence in oral HPV infection and in HPV-positive oropharyngeal cancer in the United States. "The curves are a little bit frightening," said lead author Maura Gillison, MD, PhD, from Ohio State University in Columbus. But she pointed out that vaccines against HPV are already marketed, so "we have the means to prevent this already sitting on our pharmacy shelves."
The HPV vaccines (Gardasil and Cervarix) were developed to offer protection against cervical cancer after the link between cervical HPV infection and cervical cancer was firmly established, and are targeted mainly to girls.
The link between oral HPV infection and oral HPV cancer was established more recently; Dr. Gillison reported that the research is about 20 years behind that for cervical cancer. There is speculation — although no hard data — that the same vaccines could offer protection against HPV-associated oral cancer. Because this is more prevalent in men, it would make sense to vaccinate boys as well as girls.
"We need to have thorough and accurate discussions about HPV vaccination," Dr. Gillison said. "We have identified a new cancer...and we have identified its Achilles heel," she added.
Dr. Gillison spoke at a presscast at the 2012 Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Therapeutic and Radiation Oncology and held in Phoenix, Arizona. The study was published online January 26 in JAMA: The Journal of the American Medical Association to coincide with its presentation.
Sexual Transmission
This the first major prevalence study of oral HPV infection in the United States, according to anaccompanying editorial, subtitled "Hazard of Intimacy."
Editorialist Hans Schlecht, MD, MMSc, from Drexel University College of Medicine in Philadelphia, Pennsylvania, writes that the "results are remarkable for a number of reasons," including the fact that they allow estimation of oral HPV prevalence based on sexual experience, smoking status, and immune suppression.
One of the main findings from this study is that the main method of transmission is sexual, and that the prevalence of oral HPV infection increases with the number of sexual partners reported.
Another finding is "a striking bimodal pattern with age" in men, with peaks in men 30 to 34 and 60 to 64 years of age.
During the presscast, Dr. Gillison speculated that these peaks in oral HPV infection might be partially explained by a "birth cohort" effect. The peak in older men could be related to the fact that they would have been making their sexual debut during the sexual revolution of the 1960s; the dip in middle-aged men could be the result of the dampening impact that the HIV epidemic had on sexual behavior. The peak in younger men could be related to one result of that epidemic — the perception that oral sex is "safe sex."
The new data showing a rising incidence of HPV oropharyngeal cancer raise questions about exactly how safe oral sex is.
In his editorial, Dr. Schlecht suggests that "clinicians should encourage their patients who engage in oral sex to use barrier protection."
First Major Prevalence Study
This study used 2009/10 data from the National Health and Nutrition Examination Survey (NHANES), and analyzed tissue collected from an oral rinse and gargle collected from 5579 people 14 to 69 years of age.
The overall prevalence of HPV oral infection was 6.9%; the particular strain associated with oropharyngeal cancer, HPV16, was found in 1%. "Although this 1% may sound small, this means that around 2.1 million individuals in the United States are infected," Dr. Gillison explained.
However, the incidence in men is significantly higher than it is in women (10.0% vs 3.6%; P < .001).
In addition, the bimodal distribution, with peaks in younger and older individuals, was seen only in men. Why the incidence of oral HPV infection in men is so much higher is not clear, Dr. Gillison said.
Men did report having more sexual partners than women, but this difference in sexual behavior explains only about 16% of the difference in prevalence, the authors note. Another explanation could be higher rate of transmission to men performing oral sex on woman than to women performing oral sex on men; there is some evidence for this in the data. But there are also many other factors, including the fact that women who have already been exposed to cervical HPV infection have greater protection against subsequent oral HPV infection.
The bimodal distribution of oral HPV infection in men is different than that of cervical HPV infection, which peaks in women in their 20s and then generally drops off, although a later peak in older women is seen in some populations.
"It is clear that the natural history of HPV is different in the 2 genders," Dr. Gillison reported.
There was a higher prevalence of oral HPV infection in black than in white people, although this did not reach statistical significance (10.5% vs 6.5%; P = .06). There was also a higher prevalence in current smokers and heavy consumers of alcohol (which increased with intensity of use for both), as well as in current and former marijuana users.
There was little HPV oral infection in individuals who had no history of any sexual contact. Compared with this group, the prevalence was 8 times higher in sexually experienced individuals, and increased significantly with the number of sexual partners. For instance, the prevalence was 20% in people who reported having more than 20 sexual partners.
"These data indicate that transmission by casual, nonsexual contact is likely to be unusual," the authors write.
They note that previous studies have suggested a link between oral sexual behavior and an increased risk for HPV-positive oropharyngeal cancer, but the way the data were collected in the current study precluded association with any particular behavior. However, the data did show that oral HPV infection is more common in sexually experienced people who do not report performing oral sex than in those who were not sexually experienced, which suggests that transmission occurs through other sexually associated contact, such as deep kissing.
This adds weight to the notion that HPV vaccination should be targeted at individuals who are 9 to 13 years of age, in an effort to reach them before any sexual behavior, including deep kissing, begins. This suggestion has been made previously by Dr. Gillison, although she emphasized that protection against oral HPV infection with the existing HPV vaccines has not been proven. She has been trying to conduct such a study for the past 5 years, but has run into funding problems; she hopes to hear soon about funding from the National Cancer Institute, she told journalists in the audience.
Extending HPV vaccination to offer protection against oropharyngeal cancer was discussed by several experts, in addition to Dr. Gillison, last year when it was highlighted by the American Society for Clinical Oncology.
The study was supported by an unrestricted grant from Merck, and was also funded by Ohio University and the Intramural Research Program of the National Cancer Institute. Dr. Gillison reports acting as a consultant to Merck and GlaxoSmithKline, both manufacturers of HPV vaccines. Dr. Schlecht has disclosed no relevant financial relationships.


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