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Oral Cancer In Men Associated With HPV
  "HPV can enter the mouth during oral sex"....
"A study published in February by researchers at Johns Hopkins estimated that 38 percent of oral squamous-cell cancers are HPV related, and suggested that their increasing number might be a result of changing sexual behaviors."....''The high risk of HPV-associated cancers in men suggests that vaccinating all adolescents is something that should strongly be considered,''
NY Times May 13, 2008
The sexually transmitted virus called HPV, for human papillomavirus, is well known to lead to cervical cancer in women -- which is why the federal government recommends that all girls be vaccinated for HPV at 11 or 12, before they become sexually active.
Now researchers are finding that many oral cancers in men are also associated with the virus.
A clinical trial testing therapies for advanced tongue and tonsil cancers has found that more than 40 percent of the tumors in men were infected with HPV. If there is good news in the finding, it is that these HPV-associated tumors were among the most responsive to treatment.
Of an estimated 28,900 cases of oral cancer a year, 18,550 are in men.
''The high risk of HPV-associated cancers in men suggests that vaccinating all adolescents is something that should strongly be considered,'' said the lead researcher, Dr. Francis P. Worden, a clinical assistant professor of medicine at the University of Michigan.
HPV can enter the mouth during oral sex. A study published in February by researchers at Johns Hopkins estimated that 38 percent of oral squamous-cell cancers are HPV related, and suggested that their increasing number might be a result of changing sexual behaviors.
The new study, published in two papers in The Journal of Clinical Oncology, included 51 men and 15 women with cancers of the tonsils or the base of tongue. The researchers were able to examine biopsies of 42 of the subjects before treatment. After tests for HPV, the researchers found that 27 tumors, nearly two-thirds, were positive for the virus. Of the 51 men, researchers found 22 with HPV.
Other experts found the results interesting, but said it was unclear what they would mean for treatment. Finding the answer to that question is the next step, said to Dr. Maura L. Gillison, an associate professor of oncology at Johns Hopkins who was not involved in the study.
''Clearly,'' Dr. Gillison added, ''it should give people optimism that the vaccine that was approved largely for women and for cervical cancer could have broader implications, and also for other cancers that occur in both men and women. All of our clinical trials now will be designed for either HPV-positive or HPV-negative patients. Right now, these patients are treated the same way.''
All the patients in the study were initially treated with induction chemotherapy, that is, an initial course to shrink the tumor. Those whose tumors did not shrink by at least 50 percent, 12 patients, were then treated with surgery. Most of those did not survive their illness.
Of the remaining group, 49 of 54 responded to the next step, combined chemotherapy and radiation. In that group, 78 percent needed no surgery, and 70 percent survived more than four years. Of the 49, almost half, 24, were positive for HPV, and all but 3of those were men.
People with tumors with high HPV levels were significantly more likely to respond to treatment. They were also more likely to survive their cancer and to survive over all.
The researchers also tested these tumors for the presence of four genetic markers: EGFR, a cell receptor associated with various cancers; BCLXL, a repressor of cell death; and the tumor-suppressor proteins p53 and p16. The scientists found that these were also accurate predictors of the success or failure of the treatment. Women and smokers were less likely to be treated successfully.
''Patients who have HPV infections are at higher risk for these cancers,'' Dr. Worden said. ''But the good news is that if that's the cause of their cancer, they're more likely to survive treatment. We still don't know what the ideal treatment regimens are. For example, these patients may benefit from less intense chemotherapy and radiation.''
Although the researchers acknowledge that the number of patients in their study was small, they conclude that especially in patients with HPV-positive tumors, chemotherapy followed by combined chemotherapy and radiation appears to be an effective treatment.
An author of the papers has an interest in a company that is developing an HPV detection method.

New Oral Cancer Tests: Crucial or Wasteful?
NY Times February 2, 2009
Despite the many advances against cancer in recent decades, the statistics on this form of it remain discouraging: more than 60 percent of cases are diagnosed in the late stages, and the five-year survival rate is a disappointing 59 percent. Moreover, oral cancer is increasing in people traditionally at low risk, a phenomenon partly attributed to the rise of the cancer-causing human papillomavirus, or HPV, which can be transmitted through oral sex.
Now some dentists - whose visual examinations have long been a first line of defense against oral cancer - are using screening devices that they say may help identify cancers and premalignant lesions.
But these new tests have set off a debate over cost and effectiveness. Experts are divided on whether they will reduce mortality from oral cancer or simply lead to a wave of expensive and unnecessary biopsies.
An estimated 35,300 Americans learned they had oral cancer last year, and about 7,600 died from the disease. For survivors, oral cancer can be painful and disfiguring, and can destroy the ability to taste and enjoy food. Smokers and heavy drinkers are considered at highest risk for the disease, but 25 percent of those who receive a diagnosis are neither. Still, the lifetime risk of oral cancer - about 1 in 99 - is very low compared with breast and prostate cancer.
Because the disease is often diagnosed late, many experts believe that screening can reduce mortality. This has not been proved, partly because there is a dearth of research on oral cancer.
Indeed, no one knows for sure whether even a visual examination in the dentist's office saves lives, though most oral cancer experts believe it does. That hypothesis is based on the proven benefits of early detection of other cancers and the better survival rates in cases that are detected early - about 80 percent five years after diagnosis.
"We know in every cancer where we've seen a reduction in the death rate - cervical, skin, breast - that what has brought the death rate down is early detection," said Brian Hill, an oral cancer survivor from Laguna Niguel, Calif., and a founder of the Oral Cancer Foundation, a nonprofit group.
One large study from India, where oral cancer rates are much higher than in the United States, found that when high-risk subjects had a visual exam, it reduced the mortality rate by 34 percent compared with control subjects who were not screened. But some experts say this research cannot be applied to the general population or to Americans.
The American Cancer Society and the American Dental Association recommend a regular visual exam. But even though it is generally covered by insurance, not all dentists perform it.
"Studies show that most dentists don't leave dental school feeling comfortable doing it," said Dr. Michael A. Siegel, a professor and the chairman of diagnostic sciences at Nova Southeastern University College of Dental Medicine in Fort Lauderdale, Fla.
Now medical companies are marketing several new screening tests and devices to dentists, saying they will vastly improve early detection of oral cancer. The devices, which can cost several thousand dollars, use rinses, dyes and different types of lights to detect abnormal cells.
Some experts say the new technology will lead to earlier detection, if only by encouraging dentists to do a screening exam. "The tests change the paradigm by which they practice," Dr. Siegel said. "Simply because it's new, they say, 'I'm going to use it.' "
They can also charge for the test, and some insurers have started covering it.
"We're advocates of using these devices because there are some things your eye might miss," Mr. Hill said.
Yet no extensive studies of the general population show that these devices are any better than the naked eye for screening, and they have not been shown to reduce mortality.
"There's no evidence for their use by front-line screeners, no evidence," said Dr. A. Ross Kerr, an assistant professor at the New York University College of Dentistry.
In small studies, the devices successfully detected potentially malignant lesions that experienced specialists missed with the naked eye. For example, in one group of subjects a scanning system called the VELscope identified all of the cases of moderate to severe dysplasia, or potentially precancerous cells, compared with just 68 percent for a visual exam, said the study's author, Dr. Edmond Truelove, a professor and the chairman of oral medicine at the University of Washington. (Dr. Truelove does not receive financing from LED Dental, the company in British Columbia that makes the VELscope.)
Another study of 688 high-risk patients examined by experienced specialists found that when only a visual exam was performed, the specialist requested a biopsy of 12 of the 30 lesions that turned out to be cancerous. Of those who also used toluidine blue, a dye that is a component of a test called ViziLite Plus, 29 of the 30 lesions would have been biopsied, said the study's author, Dr. Joel Epstein, a professor of oral medicine at the University of Illinois, Chicago.
But he added, "What we don't know is what happens if we use the same technique in a low-risk population by people with less experience." (Dr. Epstein said that in the past he had received compensation from Zila Pharmaceuticals, which makes ViziLite, and is currently receiving financing from the company for a small study.)
The screening tests can cost the patient $35 to $65, though some dentists do not charge extra for it. And the tests have a high false-positive rate that may lead to unnecessary biopsies. If a suspicious lesion is detected, dentists typically ask the patient to return in two weeks to see if it has improved. If not, the patient may be given a biopsy or referred to a specialist.
Some dentists are telling their patients that because of the rise of oral cancers linked to HPV, every adult, not just the traditionally high-risk groups, should be screened with these devices.
Yet oral cancers associated with the papillomavirus are still rare, and they typically occur near the base of the tonsils and the back of the tongue, where they are very difficult to see at the earliest stages, even with the use of these devices, said Dr. Maura L. Gillison, a professor of medicine at Ohio State who is a leading expert on oral HPV.
Dr. Mark Lingen, an associate professor of pathology at the University of Chicago Medical Center, agreed. "If you can't get back there to see it," he asked, "how is that device going to help you?"
But Dr. Epstein says the devices may help. "If you're someone with a high risk of HPV exposure, meaning that you've had oral sex with multiple partners, you need to be examined carefully," he said. "Higher-risk people could maybe benefit from some of these adjuncts."
Dr. Truelove, who did the VELscope study, said he would not recommend expensive screening for normal individuals, but he added, "On the other hand, a low-cost test, say $5, that enhances a clinician's ability to detect something they might otherwise miss is potentially useful, particularly in people who have some increased risk of the disorder."
Researchers are working on the holy grail of oral cancer screening: a test that can analyze saliva for early gene changes that could lead to the disease.
Most experts agree that everyone should have an annual visual exam and that it should be thorough. A dentist or trained hygienist should examine the cheeks, the gums, the floor of the mouth, the area behind the teeth, the palate and the tonsil area, pulling the tongue forward - often to the point of gagging. The dentist should also feel the lymph nodes of the neck, sometimes the first visible sign of oral cancer.
"The emphasis should also be placed on educating physicians about oral cancer," said Dr. Kerr, of N.Y.U. Only 60 percent of adults see a dentist at least once a year, he continued, adding, "The 40 percent who never go to the dentist are likely to have the highest risk factors.
"When I teach my students," he said, "I say at the end of the day, all you need is to have one patient with an early cancer that you picked up and you will do this for the rest of your career."
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