July 30, 2009 — Clinicians who diagnose oropharyngeal cancer should now test their patients' tumor tissue for human papillomavirus (HPV), say experts. HPV-positive cancers of the head and neck have dramatically better prognoses and are more responsive to chemotherapy and radiotherapy than HPV-negative cancers, which have a poor prognosis, experts noted at a press conference organized by the American Association for Cancer Research.
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| Dr. Kevin Cullen (Courtesy of American Association for Cancer Research) |
"Clinicians can tell the HPV-positive patient, 'You are going to do very well on chemotherapy and radiation'," said Kevin Cullen, MD, from the University of Maryland Marlene and Stewart Greenebaum Cancer Center in Baltimore. He also said that patients with HPV-negative oropharyngeal cancers should explore the option of surgery and other alternative treatments.
The recommendation to test for HPV status is not new. As previously reported by Medscape Oncology, HPV and oropharyngeal cancers have been linked for some time. However, a new study led by Dr. Cullen makes an important contribution to the understanding of this link, which is why this study was the focus of the press conference.
The study shows, for the first time, that the well-known difference in survival between black and white patients with squamous cell carcinoma of the head and neck is related to HPV status in a subset of these cancers — specifically those that are oropharyngeal (at the base of the tongue and on the tonsil).
The difference in survival is actually not racially based. Instead, it is due to the fact that blacks are much more likely to have difficult-to-treat HPV-negative oropharyngeal cancer than whites, and thus have greater mortality, said Dr. Cullen. The study was published online July 29 in Cancer Prevention Research.
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| Dr. Otis Brawley (Courtesy of American Association for Cancer Research) |
The study was hailed as both "practice changing" and an "extremely important finding with tremendous public-health implications," by Scott Lippman, MD, from the University of Texas MD Anderson Cancer Center in Houston, who moderated the press conference and is editor-in-chief of Cancer Prevention Research.
HPV is not protective. It just causes a different kind of cancer that has a more favorable outcome.
Some of the public-health implications arise from the fact that HPV is an infection, and its increasing presence among patients with oropharyngeal cancer seems to be tied to the rise in oral sex among young whites — but not blacks — in the United States. "A search of the literature that oncologists do not read shows that sexual practices can differ by race," notes Otis Brawley, MD, from the American Cancer Society in an accompanying editorial. Other public-health implications are related to the fact that oropharyngeal cancer that is HPV-negative is likely to be a consequence of alcohol and tobacco use.
Dr. Brawley pointed out that an oral-sex-acquired HPV infection is in no way helpful. "HPV is not protective. It just causes a different kind of cancer that has a more favorable outcome," he said.
How They Discovered the Link
The new study and its conclusions come from both retrospective and prospective data.
In a retrospective analysis of 106 blacks and 95 whites with squamous cell carcinoma of the head and neck treated at the University of Maryland, the investigators found that the 2 groups had very different survival: for blacks, median survival was 23.7 months; for whites, it was 52.1 months. However, the investigators then decided to consider the racial difference specifically for oropharyngeal cancer. When they did this, the difference in median survival widened further: for whites, it was 69.4 months and for blacks it was 25.2 months.
"We then realized that if we took out all of the cases of oropharyngeal cancer, the survival differences between blacks and whites might disappear," said Dr. Cullen. Sure enough, among the cases of nonoropharyngeal cancers, the median survival was nearly identical: for whites it was 17.1 months and for blacks it was 17.5 months.
There was no survival difference between blacks and whites with head and neck cancers of the nonoropharyngeal type; the survival difference between races was confined to oropharyngeal cancer.
This led the investigators to examine pretreatment biopsy specimens from a prospective trial of head and neck cancers, known as TAX 324, in which patients were treated with chemotherapy and radiation (N Engl J Med. 2007;25:1705-1715).
In TAX 324, 196 white patients and 28 black patients were assessed for HPV status, write Dr. Cullen and his coauthors.
As with the University of Maryland data, the median overall survival in TAX 324 was significantly worse for black patients (20.9 months) than for white patients (70.6 months; P = .03).
However, patients with HPV-negative oropharyngeal cancer — regardless of race — had worse outcomes than patients with HPV-positive cancer. HPV-negative patients had a median survival of 26.6 months, whereas the survival rate for HPV-positive patients could not be calculated because most were still alive.
We need to think of HPV-positive and HPV-negative patients as having 2 different diseases.
In short, the survival dramatically improved in HPV-positive oropharyngeal patients, compared with HPV-negative patients.
Overall, 4% of black patients and 34% of white patients were HPV-positive. Blacks fared worse in the study than whites because they were more likely to have the difficult-to-treat HPV-negative cancer. In other words, survival and oropharyngeal cancer is not really a matter of race but of whether or not a patient has HPV infection.
"We need to think of HPV-positive and HPV-negative patients as having 2 different diseases," said Dr. Cullen.
A Changing Demographic, Oral Sex and a Possible Epidemic
At the press conference, Dr. Cullen provided some background on head and neck cancer. "About half of all head and neck cancer is oropharyngeal, and about half of those oropharyngeal cancers are HPV-related," he said.
The typical profile of a patient with oropharyngeal cancer has greatly changed in the past 20 years or so, said Dr. Lippman.
In the past, the disease was primarily that of older patients and was related to tobacco and alcohol use; their disease was typically HPV-negative. In recent years, "the demographics are totally different," said Dr. Lippman. Patients tend to be executives, educated, white, and in better shape, he said. They are also likely to be HPV-positive.
The experts at the press conference suggested that the increase in the practice of oral sex among white, especially younger, Americans, has led to the increasing incidence of oral HPV infection and related HPV-positive oropharyngeal cancer.
Young black Americans are less likely to have oral sex and they are more likely to first have genital sex, said Dr. Brawley. This might explain why blacks are less likely to have HPV-positive oropharyngeal cancer. In the case of black Americans, their HPV infections are more likely to be genital, which in turn provides them with some immunity in the oral cavity. Thus, when blacks have oropharyngeal cancer, it tends to be the difficult-to-treat HPV-negative type, he explained.
Why exactly HPV-positive oropharyngeal cancer is more responsive to treatment is not known, said Martin Blaser, MD, from New York University Langhorne Medical Center in New York City.
Dr. Lippman warned of a potential "epidemic" of oropharyngeal cancer. "This is likely to become one of the most common cancers we see," he said.
Vaccination for HPV is a likely strategy to deal with HPV-related oropharyngeal cancer, said Dr. Brawley. One of the targets of HPV vaccination, HPV-16, is associated with a significant percentage of oropharyngeal cancers, he said. Both boys and girls would receive vaccinations as part of such a strategy, he added.
The researchers have disclosed no relevant financial relationships.
Cancer Prev Res. Published online before print July 29, 2009.
