B.C. detection test being used to catch oral cancer in early stages

Author: staff

Doctor says oral cancer is among the deadlier diseases yet rarely talked about.


The Canadian Cancer Society estimates 4,400 people will be diagnosed with oral cancer this year. The deadly disease can often go undiagnosed because it is tough to screen for dormant symptoms. But now, researchers at the University of British Columbia (UBC)  are developing a new test that will be able to detect oral cancer at a much earlier stage.

Dr. Catherine Poh, an oral pathologist who also teaches dentistry at UBC, spoke with the Early Edition’s Rick Cluff about the latest developments.

What can you tell us about this new brushing test you’re working on?
We are a proposing a non-invasive approach to analyse genetic material collected from patients mouths using a simple brush. This can be done by a dentist or at a family doctor’s office.

This test would detect genetic change that happens in human genomes from the cells collected from the mouth. We have shown that it has prediction value for the risk for oral cancer development.

How does your test compare to how oral cancer is detected right now?
Right now the majority of oral cancer has been screened by dentists because many of the oral cancer [diagnosis] come with no pain or no symptoms. Through the dental regular checkups it can be detected early, otherwise patients come with a sore in their mouths that is essentially a delay in the diagnosis.

What symptoms should people look out for?
Many people know your mouth can be sore and that’s not a sign of oral cancer. I’m suggesting people look for a mouth sore that doesn’t heal within three to four weeks or there’s colour change with white or red bumps that don’t get resolved. [This warrants a] checkup from your family dentist or doctors.

Who does oral cancer affect?
Traditionally 75 per cent are smokers and drinkers, however we’re aware there are a number of rising incidents within the younger non-smoker, non-drinker group. Studies show increasing risks of tongue cancer for women aged 18 – 44.

We don’t know [the exact reason] yet. There are people talking about chronic inflammation and infection so we are looking for more details into that aspect.

If it is caught early on, what does that mean for someone’s chances of beating cancer?
Right now, 1 in 2 patients will die in five years so it’s a deadly disease. If caught early…the chance for easier treatment increases. Early detection is the key to really improve a better outcome.

We promote that patients over 80 should have a regular check up for the disease with their family doctor.

Canadian court orders three major tobacco companies to pay billions in damages

Author: Natalie Alcoba



Three tobacco giants have been ordered by a Canadian court to pay billions of dollars in moral and punitive damages to nearly 100,000 smokers, in what has been hailed as an “historic judgment” by the plaintiffs in Quebec.

Imperial Tobacco Canada, Rothmans, Benson & Hedges, and JTI-Macdonald were found to have violated their general duty not to cause injury to another, their duty to inform their clients of the risks and dangers of their products, and their obligation not to mislead their clients. A Quebec Superior Court slapped the three cigarette manufacturers — which have already vowed to appeal — with damages totaling CAD $15.5 billion ($12 billion US), to be split among them.

The ruling means that plaintiffs suffering from lung or throat cancer are entitled to receive CAD $80,000 or $100,000 ($63,000 or $80,000), while those afflicted with emphysema can receive CAD $24,000 or $30,000 ($19,000 or $24,000), plus the interest accumulated since 1998, which is when the lawsuit commenced.

“Today marks an important day for the victims of tobacco who have waited almost 17 years for this moment”, said Mario Bujold, executive director of the Quebec Council on Tobacco and Health on Monday.

Imperial Tobacco was held responsible for CAD $10.5 billion ($8.3 billion), while Rothmans, Benson & Hedges bear responsibility for CAD $3.1 billion ($2.4 billion), and JTI-Macdonald the remaining CAD $2 billion ($1.6 billion).

“By choosing not to inform either the public health authorities or the public directly of what they knew, the Companies chose profits over the health of their customers,” Justice Brian Riordan wrote in his 276-page judgment. “Whatever else can be said about that choice, it is clear that it represent a fault of the most egregious nature and one that must be considered in the context of punitive damages.”

Two class actions were heard as part of the same trial. One, spearheaded by the Council, included 99,957 Quebec smokers and ex-smokers who had developed emphysema, lung cancer, or throat cancer. A second class action was much broader, representing 918,218 people addicted to tobacco in Quebec. While the Quebec Council on Tobacco and Health said the judge sided with the plaintiffs in both cases, only those in the first group will receive compensation.

But Rothmans, Benson & Hedges said the cases are “far from over”, a sentiment shared by the other manufacturers.

“We will vigorously appeal this lower court’s judgment, and believe that we have very strong legal grounds to overturn the judgment in its entirety,” RBH spokeswoman Anne Edwards said in a statement.

She noted that not a single class member, in nearly three years of trial, “showed up to say that he or she was unaware of the risks of smoking,” and said given the “prevailing law and common sense” the judgement should not stand.

JTI-Macdonald Corp. also said it “fundamentally disagrees” with the judgment and intends to file an appeal.

“Since the 1950s, Canadians have had a very high awareness of the health risks of smoking. That awareness has been reinforced by the health warnings printed on every legal cigarette package for more than 40 years,” it said in a statement, adding that the company complies with all Canadian and Quebec laws.

In its statement, Imperial Tobacco Canada called it “astounding to be handed this decision when the federal government has set the standard for the conduct of Imperial Tobacco Canada with which the company has always complied.”

Still, Andre Lesperance, one of the lawyers involved in the case for the plaintiffs, said on Monday that the companies “lied” to their customers and “hurt their right to life,” The Canadian Press reported.

“It’s a great victory for victims as well as for society in general,” he said.

Keratinization may be prognostic in certain head and neck cancers

Author: T. Cooper

Keratinization may be prognostic for patients with oropharyngeal squamous cell carcinoma, according to results of a retrospective, cross-sectional study.

The greatest prognostic value may be among patients who have p16-negative and nonbasaloid tumors, as well as those who are smokers, results showed. Keratinization may result histologically following hematoxylin-eosin staining that is associated with adverse outcomes in head and neck cancers, particularly oral cavity squamous cell carcinoma.

Hadi Seikaly, MD, FRCSC, professor of surgery and divisional director and zone section head for otolaryngology – head and neck surgery at the University of Alberta, and colleagues assessed the prognostic value of keratinization in a large cohort of patients. Subgroup analyses evaluated results based on p16 status, basaloid differentiation and smoking status.

The researchers used a prospectively collected database to identify 208 patients with oropharyngeal squamous cell carcinoma diagnosed and treated at a single tertiary cancer center between 2002 and 2009. The mean age of the patients was 58.4 years (range, 32-95 years), and the male-to-female ratio was 3.4 to 1.

The analysis included 146 smokers, 59 nonsmokers and three participants for whom smoking data were not available. Tissue microarrays were generated from each patient’s specimens stained with hematoxylin-eosin and immunohistochemical markers. Each image was scored for the presence of keratinization and/or basaloid differentiation, as well as p16 status.

Five-year disease-specific survival based on keratinization served as the primary outcome measure. Of the 208 samples, 112 were nonkeratinizing. The 96 patients with keratinizing samples were more likely to have advance-stage disease and be p16-negative.

The rate of 5-year disease-specific survival was significantly higher among those with nonkeratinizing tumors compared with those that were keratinized (63.3% vs. 44.8%; P=.007), the researchers said.

Results of subgroup analyses showed nonkeratinization was linked to better disease-specific survival among patients with p16-negative and nonbasaloid tumors, as well as among those who were smokers.

Patients who smoked and had p16-negative keratinizing tumors demonstrated the lowest rate of 5-year disease-specific survival (26.7%) among any subgroup.

One of the researchers reported an unpaid consultant role with and travel reimbursement from AstraZeneca.

Cooper T. JAMA Otolaryngol Head Neck Surg. 2015;doi:10.1001/jamaoto.2014.3335

January, 2015|Oral Cancer News|

Government anti-smoking campaign cost just $480 per quitter, study finds

Author: Lenny Bernstein

At $48 million, the first government mass media campaign to convince cigarette smokers to quit would seem a pricey luxury, especially since that sum purchased just three months of television ads from March through June of 2o12. But a new study of its cost effectiveness, released Wednesday, determined that it cost just $480 for each smoker who quit and $393 per year of life saved.

The graphic videos featured pleas from former smokers who had suffered amputated limbs, oral and throat cancer, paralysis, lung damage, strokes, and heart attacks. One of the most haunting showed Terrie Hall, a 52-year-old North Carolina woman whose larynx was removed after she was diagnosed with throat cancer. In the ad, she spoke with the help of an artificial voice box. Hall later died.

The campaign and the analysis were both conducted by the Centers for Disease Control and Prevention, but Saul Shiffman, a University of Pittsburgh psychology professor who has spent decades studying smoking habits, said there is no doubt it was a tremendous bargain for the public and, especially, the smokers who quit or added years to their lives. One standard used in studying such interventions considers them cost effective at $50,000 per year of life gained–more than 100 times the cost of the campaigns.

Medical interventions, such as heart and lung surgery commonly needed by long-term smokers are much more expensive than that, Shiffman noted. The money spent on the campaign “would pale next to the money we spend for medical treatment for smokers who otherwise are going to have a heart attack and lung cancer,” he said.

CDC Director Thomas Frieden said the campaign is “an example of an investment that saves lives and money. Most smokers want to quit. Tips show that people can, and can save literally tens of thousands of lives, and has done so at a cost vastly lower than the cost of most other health interventions.”

Shiffman and Tim McAfee, director of the CDC’s Office on Smoking and Health, noted that the tobacco industry spends about $8 billion annually to promote its products. Funding for the campaign, which continued in subsequent years, comes from the Affordable Care Act.

A previous study of the effort determined that more than 100,000 people gave up smoking for six months or more, considered permanent abstinence for the purposes of the research. Another 100,000 quit for shorter periods of time and 1.6 million tried to quit after seeing the ads.

The data was derived by surveying a group of several thousand smokers before and after the ad campaign, McAfee said. About 89 percent said they had seen the ads.

The shocking nature of the campaign was designed to reach smokers, who already know that the habit is likely to sicken and kill them. They told researchers “we don’t want to die early , but we’ve kind of absorbed that message. We don’t want to suffer and we don’t want our families to suffer,” McAfee said.

“What they told us [was you] need to show us in a way that we can understand or believe what the consequences of us continuing to smoke are,” he said. A positive message was included at the end of the ads to highlight the fact that even smokers who quit late in life improve their health and gain quality of life, he said.

Despite declines in smoking rates, about 42 million people in the United States, 18 percent of the population, still smoke. The habit remains the single most preventable cause of death and disease in this country, the study noted.

December, 2014|Oral Cancer News|

Cigarette smoking caused 14 million serious diseases in 2009

Author: Larry Hand

Cigarette smoking remains a major cause of preventable diseases in the United States, with at least 14 million serious medical conditions attributable to smoking in 2009, according to an article published online October 13 in JAMA Internal Medicine.

“These estimates demonstrate that smoking accounts for millions of serious medical conditions in the United States that could be avoided in the absence of cigarette use,” write Brian L. Rostron, PhD, from the Center for Tobacco Products, US Food and Drug Administration, Silver Spring, Maryland, and colleagues. “Our results also indicate that previous estimates may have substantially underestimated smoking-attributable morbidity in the United States.”

The researchers analyzed multiple sources of data from 2006 to 2012, including 2009 population data from the US Census Bureau, smoking prevalence and disease risk from the National Health Interview Survey of US adults for 2006 to 2012, and data from the National Health and Nutrition Examination Survey of US adults for 2007 to 2010.

Current and former smokers were significantly more likely to have at least one smoking-attributable disease and multiple smoking-related conditions compared with never-smokers. Specifically, almost half of surveyed men and women (47.5% and 44.9%, respectively) aged 65 years and older reported having one or more smoking-related disorder, and almost 17% of men and more than 14% of women reported having multiple such disorders. In contrast, among never-smokers, 34.9% of men and 33.2% of women reported at least one such condition and 9.1% and 7.5%, respectively, reported two or more conditions.

Rates of smoking-related conditions were also elevated among current and former smokers aged 35 to 64 years compared with never smokers. For example, almost 12% of adults at least 35 years old reported having diabetes. The adjusted prevalence ratio compared with never-smokers was between 1.17 and 1.30. The researchers also found high prevalence ratios for lung cancer (range, 4.45 – 9.35) and chronic obsessive pulmonary disorder (COPD; range, 2.02 – 4.00).

Extrapolating from National Health and Nutrition Examination Survey data on COPD prevalence, the researchers estimated 14 million “lifetime major medical conditions” could be attributed to the effects of cigarette smoking in 2009 (95% confidence interval, 12.9 – 15.1 million).

The Centers for Disease Control and Prevention previously published estimates of 8.6 million adults having 12.7 million smoking-attributable conditions in 2000.

The recent US Surgeon General’s report “concluded that previous estimates of the disease burden of smoking could be substantial underestimates, given the absence of several major medical conditions caused by smoking,” the researchers write.

Updated, Expanded
The current report is based on data from about 180,000 people surveyed between 2006 and 2012 compared with previous Centers for Disease Control and Prevention estimates based on data from about 20,000 adults surveyed between 1988 and 1994. The current report is also based on calculations for full variance, which is not generally done, the researchers write. The new report also corrects for underreporting of COPD in self-reported survey data, they add.

“Our study confirms that cigarette smoking remains a major cause of preventable disease in the United States,” the authors conclude. “The resulting estimate indicates that the number of major smoking-attributable medical conditions in the United States is larger than has been previously reported, demonstrating the need for vigorous smoking prevention efforts. The disease burden of cigarette smoking in the United States remains immense, and updated estimates indicate that COPD may be substantially underreported in health survey data.”

Work Remains
In an accompanying commentary, Steven A. Schroeder, MD, from the Division of General Internal Medicine at the University of California, San Francisco, writes that in general, the prevalence of smoking has declined, but that this “decline is excruciatingly slow, and there are still more than 40 million smokers in the United States.” Much of current smoking is among “hard-to-reach” populations, he adds.

He concludes, “Tobacco control has been called one of the most important health triumphs of the past 50 years. Yet, although we have come a long way, there is still much more to be done, with the number of smokers worldwide now just short of 1 billion people.”

Source: JAMA Intern Med. Published online October 13, 2014

October, 2014|Oral Cancer News|

Hard-to-watch commercials to make quitting smoking easier

Author: Andrew Adam Newman

Telling smokers that their habit shortens life expectancy by at least 10 years might seem like an effective way to get them to quit. But it turns out there is something even scarier: living with disfiguring disease.

Dr. Tim McAfee, the director of the Office on Smoking and Health at the Centers for Disease Control and Prevention, was overseeing focus groups of smokers to help shape a smoking-cessation advertising campaign in 2011 when this became clear.

“Telling smokers that you’re going to lose 11 to 12 years of your life expectancy if you continue to smoke, and that if you quit in your 30s you can gain 10 of those back, seemed pretty powerfully motivating to us,” said Dr. McAfee.

But smokers’ response to such messages was that it would not happen to them, Dr. McAfee said. What they feared more than an untimely death, it turned out, was chronic illness.


“They were less motivated by the fear of dying than the fear of suffering, of disability, of disfigurement, and of being a burden to those around them,” Dr. McAfee said.

Introduced in 2012, the C.D.C. campaign, “Tips From Former Smokers,” by Arnold Worldwide in Boston, features people who did not quit until smoking had taken a grave toll. The ads ostensibly offer practical advice about how to function with smoking-related ailments, but the real message is to avoid such predicaments by kicking the habit.

A new series of commercials includes one featuring Shawn Wright, a chef who lives in Spokane, Wash., who was 50 at the time it was shot. Mr. Wright, who started smoking at around age 14 and had a pack-and-a-half-a-day habit, lost his larynx to throat cancer in his late 40s and now has a dime-size stoma, a hole in his throat.

The commercial opens with a title card, “Tips from a former smoker,” and Mr. Wright in the shower, the water running behind him. Mr. Wright, who has a voice prosthesis implanted in his throat and must cover his stoma with a finger to speak, says with a gravelly voice, “When you have a hole in your neck, don’t face the shower head.” He is also filmed pushing a lawn mower (“Keep the stoma covered when you’re outside”) and sitting at a dining room table (“Get used to eating only soft foods”).

At the close of the spot, as he looks in a mirror, he sticks a tool with a brush on the end into the hole in his neck, saying, “Clean out your speech valve twice a day.”

Another new commercial features Amanda Brenden, of Eau Claire, Wis., who attributes smoking throughout her first pregnancy to her daughter’s being born two months prematurely and weighing only three pounds.

In the commercial, she demonstrates how she could not hold her newborn daughter, who was confined to a neonatal incubator. As she opens a small oval door on the incubator, tears well in her eyes. “My tip to you,” she says, “is speak into the opening so your baby can hear you better.”

Public service announcements generally rely on donated ad space, and they run infrequently and during programming with lower viewership. But the federal effort gets its funding through the Affordable Care Act, with the C.D.C. spending a total of $102.5 million to produce and place the ads in 2012 and 2013, and it is budgeted to spend an additional $60.2 million this year.

Kenneth E. Warner, a public health professor at the University of Michigan and founder of the university’s Tobacco Research Network, said funding made a big difference in the success of antismoking campaigns.

“Campaigns that are mounted by an organization that is paying for them are hugely different from other P.S.A.s, which typically rely on donated ad space and get very little time and not much coverage,” Mr. Warner said. His research suggests that well-funded antismoking campaigns are the third-most-effective measure for reducing smoking levels, behind high cigarette taxes and laws against smoking in certain places.

The 2012 C.D.C. campaign was the subject of a 2013 article in The Lancet, which credited the ads with motivating 1.6 million smokers to try to quit — with more than 100,000 of them successfully doing so. The telephone number promoted in the campaign, 1-800-QUIT-NOW, received about 365,000 calls during the 12 weeks that the ads ran in 2012, more than twice the number of calls in the same period of 2011.

To date, the campaign has featured 26 people, including a few nonsmokers who had asthma attacks because of secondhand smoke. Some of the smokers had conditions like Buerger’s disease, which may result in the amputation of limbs and extremities; oral and lung cancer; and gum disease that resulted in the loss of most or all of their teeth.

One subject of the ads, Terrie Hall, who was first featured in 2012, appeared in another ad in 2013 as her throat cancer spread to her brain. She died in September 2013, at age 53. Graphic commercials and online videos featuring Ms. Hall, who is featured posthumously in the current ads, have been viewed more than 5.5 million times on YouTube.

Mr. Wright, the throat cancer survivor shown in current ads, was filmed in 2012, when he was featured in an ad that included others with stomas, but this year marks the first time he appears solo.

Now 53, Mr. Wright said it could be difficult to watch himself in the ad.

“When I see myself in a compromising position, it does get to me a little bit,” he said. “But if people see me and know a little bit about my story, they might have second thoughts about even starting to smoke, and you just put your modesty aside when you’re doing the right thing.”

New study claims children who use snus before age 16 are more likely to become cigarette smokers

Source: Reuters Health

Author: Shereen Jegtvig

Norwegians who started using snus before age 16 were more likely to become cigarette smokers than those who started using snus later in life, according to a new study.

Snus is moist smokeless tobacco developed in Sweden. It’s contained in a small pouch, and unlike regular chewing tobacco, it doesn’t make the user spit.

Research suggests snus has lower levels of chemicals called nitrosamines than cigarettes and may be less harmful.

In Norway, snus has become a smoking cessation aid and most older snus users are former smokers.

But snus is also becoming increasingly popular among young Norwegian adults, many of whom have not smoked cigarettes. And although research is divided, the current thinking is that snus use reduces the likelihood of taking up smoking.

The authors of the new study wanted to know more about when people start using snus, to see if that ties into whether they also begin smoking cigarettes.

“I already knew about the research investigating associations between snus use and later smoking, but discovered that snus debut age had not been mentioned in that research,” Ingeborg Lund told Reuters Health in an email.

Lund is a researcher with the Norwegian Institute for Alcohol and Drug Research – SIRUS, in Oslo. She and her colleague Janne Scheffels published their study in Nicotine and Tobacco Research.

The researchers analyzed surveys of Norwegian teenagers and adults conducted from 2005 to 2011.

Out of 8,313 people, 409 were long-term snus users who had started using snus before cigarettes or never used cigarettes. Of the snus users, 30 percent were long-term smokers.

Just over one third of the snus users started using snus before age 16. The researchers discovered those participants had two to three times the odds of becoming lifetime smokers, compared to people who began using snus after age 16.

They also found that early snus users had about the same rate of cigarette smoking as non-snus users. About 23 percent of early snus users were current smokers at the time of the survey, compared to only six percent of people who started using snus when they were older.

“Snus use seems to protect against smoking if the snus debut does not happen too early during adolescence,” Lund said.

She said it’s particularly important to keep teenagers tobacco-free until they are at least 16 years old.

“At younger ages, even if they start with a low risk product such as snus, there is a high risk that they will switch to – or add – other high-risk products, such as cigarettes,” she said. “This risk is reduced when they grow older.”

Since snus use is much less common in other countries, Lund said she doesn’t know if these results can be generalized outside of Norway and Sweden.

Lucy Popova, from the Center for Tobacco Control Research and Education at the University of California, San Francisco, told Reuters Health the new study was “interesting.” She was not involved in the research.

“Earlier initiation of snus basically makes it a gateway to tobacco use, to cigarette use in the future,” she said.

Popova explained that traditional Swedish snus is less dangerous than cigarettes.

“But it’s not harm-free, and (what) is really bad is when people start using both products because of increased rates of cardiovascular disease, pancreatic cancers and other problems,” she said.

Snus is fairly new to the U.S., and Popova said the version made in the U.S. isn’t like the traditional Swedish product.

“A research study found that it’s different from the traditional low-nitrosamine snus in Sweden – it’s not necessarily going to be as low-harm,” she said.

Popova is concerned with heavy promotion for smokeless tobacco products like snus.

“There’s been a lot of studies showing that more advertisement for tobacco products makes it more likely that children will use tobacco products,” she said, “and it’s important to keep youth tobacco-free as long as possible.”

RESEARCH SOURCE: Nicotine and Tobacco Research, online February 5, 2014.

* This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

February, 2014|Oral Cancer News|

HPV alters oral-cancer expectations

Author: staff

Demographics are important to physicians.

Demographics help guide us toward more-likely and less-likely diagnoses in patients.In their most basic form, they mean we are surprised when we learn that the 90-year-old woman with hand pain suffered the injury while boxing. On the other hand, demographics are why a doctor tells the overweight man with a history of hypertension that he is “a heart attack waiting to happen.”Most disease processes can be characterized by a typical patient and are based on age, gender and sometimes ethnicity or socio-economic class.

This has long been the case with oral-cancer cases. Most physicians have an idea of a typical oral-cancer patient. We envision an older, male patient with few teeth following a lifetime of poor oral health. They generally have lower income and are lifelong smokers.

That’s why the tonsillar-cancer patient was such a surprise to me. He was 34, upper-middle class and did not smoke or drink. He had recently undergone surgery to remove his tonsils and a good portion of the back of his throat.

He had come into the emergency department that day because he was having difficulty breathing and swallowing. When I walked into the room, he was sitting on a gurney and drooling into a garbage can that he kept between his knees. The skin around his neck looked swollen and tight, leaving me to imagine how much swelling there was in the back of his throat.His surgery had been six days earlier, and he had been doing well at home until that day.

The possibilities ran through my head. Was it an infection in the soft tissue of his neck? Was it an abscess? Or was it normal post-operative changes, including inflammation? Swelling in that area heightens our level of concern for having to secure an airway. Surgically creating an airway always is a consideration.Fortunately, my patient was able to lie flat without feeling that his airway was closing.

A CT scan of his head and neck showed narrowing around his airway, but no discrete area of pus to drain. The soft-tissue swelling around the neck looked bad, but he felt comfortable as long as he sat up. We treated him with steroids and antibiotics and gave him aerosolized adrenaline to constrict the blood vessels of the airway and decrease the swelling. Within an hour, he looked much better. This patient spurred my interest. Was he a fluke?Here was a young, otherwise healthy man without risk factors for oral cancer, yet he had developed such a horrible disease. He didn’t fit any of the demographics I knew for a patient with a head and neck cancer.

The answer is that my patient is the new face of head and neck cancer. Human papillomavirus, or HPV — the same virus linked to cervical cancer in women — is being linked to oral cancers in men.Typically, 10 percent to 15 percent of the population is infected with HPV, and the incidence increases if a sexual partner is infected or the patient is HIV-positive.

HPV causes cancer in humans, monkeys, cats, dogs, cattle, mice, turtles and many other species. The literature is replete with example after example.

The incidence of HPV in humans has increased significantly. Since the 1970s, there has been roughly a threefold increase in incidence of HPV associated with tonsillar cancers.

There really is no cure for HPV once a patient is infected. We can generally live with the virus, but we are stuck with the bug and the increased risk of cancer. This is why there is such a push to prevent the infection; doing so essentially gets as close as we can to preventing cancer. There is a vaccine for the most-common causative strains of HPV associated with cervical cancer. Preventing tonsillar and oral cancers might be the next step.

Remembering my patient, I can’t help but wonder if we couldn’t have prevented some of this. More funding for research? More preventive measures? Better patient education? Yes, yes and yes.

December, 2012|Oral Cancer News|

New research reveals genetic mutations of HNC

Author: DrBicuspid Staff

New findings regarding the genetic mutations that cause head and neck cancer (HNC) may lead to new therapies, according to collaborative research presented in November at the 2012 Chemotherapy Foundation Symposium in New York City.

Aaron Tward, MD, PhD, and colleagues analyzed tumor samples provided by the University of Pittsburgh from 92 patients with head and neck squamous cell carcinoma (HNSCC), according to an article on

Patient samples were chosen to reflect the normal distribution of patients with these cancers — that is, mostly men and smokers, noted Dr. Tward. Of these patients, 89% reported a history of tobacco use and 79% alcohol use; 14% of all tumors and 53% of oropharyngeal tumors were found to be positive for human papillomavirus (HPV).

Tumor sites also were selected to be roughly representative of the general HNSCC patient population — that is, most were oral cavity cancers, followed by a substantial proportion of oropharynx cancer samples and a few from patients with hypopharyngeal or laryngeal tumors.

Investigators used hybrid capture sequencing to compare tumor tissue and nontumor tissue from the same patient. They also compared the total number of mutations in the HNSCC samples with samples from previous tumor studies.

The analysis yielded a large number of mutations. For example, 5,000 genes had at least one mutation, and 1,300 had at least two, the researchers reported. Dr. Tward emphasized, however, that most of these are not implicated either in promoting or maintaining the cancer. He said the vast majority are “passengers” — that is, mutations alongside another mutation that acts as a “driver.”

December, 2012|Oral Cancer News|

Searching for new pathways and treatments for head and neck squamous cell carcinoma

Author: Lauren M. Green

Scientists now know a lot more about the genetic landscape of head and neck cancer and hope that eventually this knowledge will lead the way to new therapies, according to Aaron D. Tward, MD, PhD, of the Broad Institute of MIT and Harvard in Cambridge, Massachusetts. Tward described findings of recent collaborative research on the topic at the 2012 Chemotherapy Foundation Symposium.

For this research, Tward, also with the Department of Otology and Laryngology at Harvard Medical School and a clinical fellow in those specialties at the Massachusetts Eye & Ear Infirmary in Boston, and colleagues analyzed tumor samples provided by the University of Pittsburgh from 92 patients with head and neck squamous cell carcinoma (HNSCC). The samples were chosen to be reflective of the normal distribution of patients with these cancers, that is, “mostly men and mostly smokers,” noted Tward. Of these patients, 89% reported a history of tobacco use and 79% alcohol use; 14% of all tumors and 53% of oropharyngeal tumors were found to be positive for human papillomavirus.

Tumor sites also were selected so as to be roughly representative of the general HNSCC patient population; thus, most were oral cavity cancers, followed by a substantial proportion of oropharynx cancer samples, and a few from patients with hypopharyngeal or laryngeal tumors, Tward explained.

Investigators used hybrid capture sequencing to compare tumor tissue with nontumor tissue from the same individual. They also compared the total number of mutations in the HNSCC samples with samples from previous tumor studies done at Broad. Tward noted that HNSCC clusters with lung cancer, in that both possess a relatively high number of mutations, sometimes referred to as “the smoking cluster.”

The analysis yielded a very large number of mutations; for example, 5000 genes had at least one mutation, and 1300 had at least two. Tward emphasized, however, that most of these are not implicated either in promoting or maintaining the cancer. “The vast majority,” he said, “are what we call ‘passengers,’ that is, mutations alongside another mutation that is acting as a ‘driver.’” Tward said his colleagues at Broad have developed a set of algorithms to help researchers distinguish between the two.

Analysis using these algorithms confirmed earlier findings implicating TP53, CDKN2A, PTEN, PI3KCA, and HRAS in head and neck malignancies. Of particular interest, however, are mutations they discovered that have not previously been implicated in these cancers: TP63, IRF6, MED1, and, notably, NOTCH.

Tward explained that NOTCH, depending on the cell in which it resides, can act either as an oncogene (as is the case with acute lymphoblastic leukemia) or as a tumor suppressor gene in HNSCC and skin cancer; in these cancers, NOTCH is “a critical player in the decision to stop proliferating,” he continued. When mutations inactivate NOTCH, terminal differentiation ceases, causing unrestrained proliferation. To illustrate the challenge posed by NOTCH’s dual mechanisms, Tward noted a clinical trial testing a gamma secretase inhibitor predicted to inhibit NOTCH in patients with Alzheimer’s disease that had to be stopped because the drug was causing an increase in squamous cell cancers in the treatment arm.

The researchers also found that mutations in genes at the “top of our rank list” for head and neck cancers and defects in squamous differentiation also are present in patients with cleft palate syndromes. “We think this is all related,” said Tward.

“When we add all this up, we come up with wiring patterns in head and neck cancer,” which can be used to inform further studies. He added that researchers did not find many oncogenes in these tumor samples, an exception being PI3KCA. Tward suggested that trials with PI3K inhibitors are likely to be fruitful in patients with HNSCC, but “only for those who have the mutation.” He also noted that investigators did not find EGFR mutations, a finding consistent with the much larger Cancer Genome Atlas (TCGA) data set.

Stransky N, Egloff AM, Tward AD, et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333(6046):1157-1160.

December, 2012|Oral Cancer News|