Hog jowls and clementines: A bid to awaken cancer patients’ ruined sense of taste

Source: www.statnews.com
Author: Eric Boodman

The medicines were rich and strange, their active ingredients so particular they sounded fictional.

neurogastronomy_illustration_mollyferguson_121616-1600x900

Credit: Molly Ferguson for Stat

One regimen involved jowl bits from Red Wattle hogs; the pigs were bred from sows named Fart Blossom and Hildegard, and had spent the end of their lives gorging on acorns, hickory nuts, apples, and black walnuts. Another experimental drug included the flesh of the Ubatuba pepper, picked when it was red as a Santa suit, dried at precisely 90 degrees for five days, and then pulverized, seeds and all, into a fragrant, pinkish powder.

These concoctions were meant to be therapeutic — but they hadn’t been devised by pharmacologists or biochemists or even lab techs. Their inventors had no scientific training whatsoever: They were celebrity Montreal chef Frédéric Morin and renowned Atlanta pastry-maker Taria Camerino, who would be facing off in an unusual culinary duel. They’d been challenged to help solve a problem that most clinicians and neuroscientists aren’t able to — the impairment of taste in cancer patients who undergo chemotherapy and radiation.

This cook-off in the University of Kentucky’s demo kitchen was the opener for the second annual Neurogastronomy Symposium, which was born over a boozy, late-night chance encounter between neuropsychologist Dan Han and Morin in the chef’s restaurant. Together, they envisioned a conference that would combine neuroscience, agriculture, history, nutrition, medicine, and cooking — to understand the art and science of why we eat what we eat, and how we could change it for the better.

It isn’t your everyday scientific conference. It’s the kind of conference where invited neuroscientists and neurologists experience the flavor wheel of bourbon, sampling Woodford Reserve along with hazelnuts and then orange flesh to see how the liquor migrates into different parts of the palate. The kind of conference where a panel discussion on the science of taste includes a hip New York chef telling a roomful of dietitians that those with binge eating problems should “have sex! It will take your mind away from food.” The kind of conference where attendees suck lollipops designed to evoke the 1812 Overture.

You know, that kind of conference.

But behind the foodie fun is hard science and a real clinical conundrum. Killing cancer cells means killing healthy cells along with them. The poisons of chemo and the waves of radiation are especially good at taking apart the DNA of fast-dividing cells. That can help stop the out-of-control expansion of tumors. But the nerve cells in the nose and mouth replenish themselves quickly, and so they die, too.

The resulting changes in taste and smell might seem like a small price to pay for a lifesaving treatment. Yet one’s desire to get up in the morning can be intimately connected to one’s ability to enjoy food. Lose your ability to taste properly and your mental and physical health — which, for cancer patients, is already fragile — can suffer even more.

“Many people stop eating,” said Gary Beauchamp, a sensory perception researcher at the nonprofit Monell Chemical Senses Center in Philadelphia. “It is a potentially lethal effect.”

The loss of taste and smell is among the most common complaints of cancer patients. But those don’t necessarily bounce back even if you’re lucky enough to transition from patient to survivor.

“The hope is that some of those taste abilities will come back. We’re all different. Some regain it very quickly; others — like myself — might not at all,” said Barry Warner, a 59-year old who was treated for throat cancer seven years ago, and one of the cook-off’s taste-testers. “The bottom line is, if after a period of time, it doesn’t come back, it’s something you’ll have to adapt to. There isn’t going to be anything the same as it was.”

Most doctors hardly ask about this side effect, and when they do, they don’t have much to offer besides apologies and explanations. Their focus is keeping you alive.

“You have no resources to help you deal with the taste aspect,” Morin said in an interview with STAT about a week before he flew to the conference, as he drove to visit a friend with late-stage metastatic cancer. “Who is the next specialist you talk to? It’s the nutritionist: an accountant of nutrition, a bookkeeper of calories. They don’t become nutritionists because they relish the smell and taste of the skin of a roast chicken.”

diamond-break

Camerino does a lot more than “relish” smells and tastes. By her own account, she lives through her sense of taste.

“I taste everything — like, everything,” she told STAT. “I taste colors, people, emotions, music … I can’t remember songs or movies, but I know what everything tastes like.”

That’s not just because she’s a celebrated pastry chef, who has devoted decades of her life to subtle differences in food. It’s also because she’s synesthetic. The unusual wiring of her brain makes her experience the world through her tongue. Sights and sounds conjure up complex flavors, allowing her to become a kind of mystical Willy Wonka, with top hat and plum velvet jacket swapped out in favor of big round glasses and snaking blue tattoos.

Camerino talks about the flavors she perceives the way some saints talk about God — as an experience accessible only through metaphor. And just as monks might interpret their visions through the lens of scripture, she uses her training in French patisserie, Japanese confectionery, and coastal Italian cooking to pinpoint what exactly it is she’s tasting at that moment — and, in some cases, to reproduce it.

When she was tasked with “profiling” the chef and television personality Andrew Zimmern in a cake, she was startled that the first thing to appear on her palate was prawn shell. “I was like, ‘Are you kidding?’” she said.

“How do I take a prawn shell and put it into a cake? You toast it. I toasted it low, for a long time, so it never burned and it didn’t become overly sharp, and then I ground it into a powder and I folded it into the cake batter, so all you got was the essence, nothing overwhelming.” The other flavors she had felt — green Szechuan peppercorns, bay leaves, miso, Asian pear — became accompanying syrups and jellies, until she was confident her cake perfectly embodied Zimmern’s spirit.

Sometimes, she’ll get flavors she’s never had before, and only through extensive research can she identify them. A band she was taste-profiling a few years ago conjured up a tang that turned out to be a Southeast Asian fruit called calamansi. A man she met around 2001 evoked a taste that turned out to be mare’s milk, as used in Tibetan and Mongolian cuisine. She is sure of it, even though she’s never tasted horse milk of any kind.

When Han, the neuropsychologist at the University of Kentucky, emailed to invite Camerino to the conference, she thought it was a joke. Like most people, she had never heard the term “neurogastronomy.” After all, it was only coined in 2011, in the title of a Yale neuroscientist’s book. She wasn’t sure that such a conference existed.

But after a back-and-forth by phone and email, she agreed. The arrangement had a fairy-tale ring to it: The woman for whom taste is everything would concoct a special dish that could rekindle patients’ pleasure in food.

diamond-break

Barry Warner’s first hint of flavor began at least as early as 1957, in the months before he was born. His mother had grown up on a farm southeast of Louisville, where dinner came from the pigpen, the cowshed, and the vegetable patch. That kind of country cooking was what she learned and continued making into her adult years, and during her pregnancy, its fragrant particles filtered down though her digestive system and into her amniotic fluid, shaping what Warner would like once he was born.

He was raised among the rolling corn and tobacco farms of Nelson County, in a small town with a single stoplight. His parents weren’t farmers, but starting at 11 or 12, he helped neighbors to bale hay, loading it into trucks and stacking it in barns for the winter. He loved his mother’s cooking: cornbread sticks made in a cast-iron skillet, cooked cabbage, pork chops soft enough to cut with your fork.

But in 2009, eating became painful. “Every time I tried to extend my mouth wide enough to take a bite out of a sandwich or a hamburger, I had a burning sensation in my tongue,” he said. He went to see a friend, an oral surgeon who’d removed his wisdom teeth years before, and asked him to take a look.

“He thought it was cancer, but he didn’t tell me that and he didn’t tell my wife until he got confirmation,” Warner said. “I didn’t know about it until then.”

Throat cancer was one assault on his body and his ability to eat, but the treatment brought about many more. Five days a week, for seven weeks, he would be immobilized onto a steel table and inserted into a machine for radiation. He also got periodic rounds of chemo.

Those didn’t just dampen his ability to taste; they also left him without saliva and made him taste flavors that weren’t there.

“It really starts out when you’re undergoing chemotherapy, that metal taste you get,” said Warner. “It seems like no matter what you eat, the taste isn’t right.”

He could have been tasting the drugs in his bloodstream — but he could also have been experiencing what some call phantom flavors. Those phantoms, some scientists say, can be the product of a taste system that is no longer in control, like a trained horse gone crazy, bucking off its rider and reverting to a frenzy of kicks and twists.

“Taste has an interesting function beyond what you experience when you eat,” said Linda Bartoshuk, a taste perception expert at the University of Florida. “Nature wants you to eat, so the taste system can be used to turn off sensations that might interfere with your eating. Taste input actually turns down pain. How does taste do that? It does that by sending a lot if inhibitory messages in the brain.”

Take away those inhibitory messages, Bartoshuk said, and those unwanted sensations come roaring in.

Warner no longer tastes those stomach-turning flavors — but he can’t taste anything else either. He might be able to identify mashed potatoes, say, by the texture, and maybe a little by the smell. But beyond that, he wouldn’t be sure what he is eating.

Now, at the lunch before the cook-off, Warner took tiny bites of the squash-and-goat-cheese appetizer that was in front of him. Partially he was saving room for the two different regimens that were on their way to try to rekindle some of those lost gastronomic pleasures for him and a fellow survivor. But that is also just how he’s had to eat since treatment: slowly, mostly without talking, and with little enjoyment, forcing himself to take one small bite after another.

“I don’t really get hungry,” he said. “You might sit down at your meal thinking about how good it tastes. Instead, I’m counting how many bites it will take me to get through it. And you never think about how much eating is part of your social life. That changes dramatically.”

Warner has kept some of his habits anyway. He still drinks bourbon socially — a taste wired into him as a Kentuckian — and he can smell it, and feel the burn of the first sip. And he still drinks a cup of coffee every morning. But he can’t taste either one.

He doesn’t complain about these long-term side effects. “I am so grateful and indebted to the doctors that saved my life, I consider my hearing loss and my loss of taste just … collateral damage,” he said. “Seven years ago, when I was getting my diagnosis, the odds of me having this conversation were less than a flip of a coin.”

Still, part of him wishes that he could experience what he remembers of food and drink. He hopes he’ll wake up one day and be able to taste his coffee.

diamond-break

Camerino has devoted herself to sweets, studying chocolate-making and practicing the way to twist a pastry bag so a spritz cookie has the perfect swirl. But suffering, loss, illness, pain — those, too, have distinct flavors for her.

She grew up in a poor, abusive household in Gainesville, Fla., with a heroin-addicted father. “Everything tasted like too-salty water, the kind that you gargle when you’re sick and you’re not supposed to drink,” she said.

She remembers a year when they ate little but white rice and packaged brown gravy. She remembers struggling through eating disorders without ever seeing a doctor. She remembers the smell of the Miller High Life her father drank. Yet she also remembers her mother getting a job at the African and Asian languages department at the University of Florida, being invited over and presented with foods she had never imagined. Those visits pushed her into studying linguistics.

It was only a chance encounter with a pastry magazine that made her switch course: “I was like, ‘That’s what I want to do. I want to create something that’s bite-sized that can change your perspective on life.’”

The invitation to the Neurogastronomy Symposium seemed like a perfect opportunity. And as with many of her concoctions, she would be guided by both her synesthesia and her culinary education. This time, though, the food would be a kind of medicine. “I’ve wanted to do something meaningful with this superpower,” she said.

She had been told next to nothing about the patients she would be cooking for. Instead, she both did external research — and turned inward. She began conjuring up the flavors evoked by cancer, by chemotherapy, by terrible pain. They were not so different from what she tasted during the long recovery from a motorcycle accident she had this summer: something acidic, a bit like blood, with an astringent metallic edge. She wasn’t surprised that this was the same taste that many cancer patients got when undergoing treatment.

“The first thing I wanted to do was dim that down. If I can gain control of the taste in their mouth, if I can get rid of it, I can give them some relief,” she said. “Blood or metal, the best way to compete with that would be citrus. I’m not using a really strong citrus: Clementines are sweet, they have a little more of a delicate flavor. The clementine will cut through — it will literally cut through — the blood and metallic taste, so now I have a pathway through into their experience.”

Yet she also knew that some patients didn’t have much sense of taste left at all, so she wanted flavors that, to her, produce vibrations felt beyond the mouth: basil and pistachio. “By using the basil, now I’m opening up from the top of the mouth to the top of the forehead, that’s where basil affects you, now I have their whole attention. And pistachio, it has a floral quality, it’s reminiscent of the Mediterranean, of the ocean.”

She wasn’t completely giving up on the mouth, though. She thought of how fat can fall soothingly on the palate, another sensation beyond taste. Butter was too heavy, too overpowering, she said. Instead she went with olive oil.

The medication she came up with would be delicate, fragrant, and not too sweet: a clementine upside-down cake with a dab of basil and pistachio pesto, crowned with a scoop of olive oil gelato.

She wasn’t sure how well it would work. She had never made it before, and had no plans to try it out before she arrived at the event. She knew nothing about these particular patients. Yet as she was preparing for the symposium, she became so excited about the idea of helping patients with taste loss that she even began to dream up a lozenge with the same goal.

“I’ve made people experience emotions by combining particular flavors,” she said. “If I’ve made them experience disappointment, satisfaction, joy, then it may be possible to activate certain parts of the brain and make them experience all of that even without their sense of taste.”

diamond-break

The day of the challenge began snowy and gray. Two days before, fatty jowl bacon had been fetched from a long-bearded breeder of Red Wattle hogs, and driven 60 miles back to Lexington, for whatever taste-saving concoction Morin, the Montreal chef, had in mind. Now, the University of Kentucky chef-in-residence Bob Perry was picking up last-minute ingredients from the research farm where the Ubatuba peppers grow.

Morin, it turns out, hadn’t really planned his dish out in advance. He’d asked for some vegetables, wine, bacon, spices. He’d figure something out. Camerino, on the other hand, arrived at the university’s demo kitchen with her own ice cream maker and a duffel bag of tools — infrared thermometers, weird tweezers, Q-tips, an offset spatula, an elaborate assortment of spoons. She was going to bring her own olive oil, too, but thought that might be overkill.

Before they headed into the kitchen, the clinicians and scientists and chefs and sommeliers gathered around Warner and another cancer survivor named Erica Radhakrishnan like overeager medical students crowding around a rare and fascinating case. They peppered the two with questions. What was their most memorable meal? Are there textures you find comforting? Did you eat processed foods before? What about the savory taste, which the Japanese call umami?

Then, with whatever intel they could gather, the chefs began to cook. Morin peeled potatoes and fried bacon. Camerino cracked eggs with a single hit on the side of the bowl, a quick squeeze and a pull.

Camerino adjusted her recipe slightly, making room for local ingredients. She incorporated a sprinkle of Ubatuba paprika into a syrup for the cake; she used molasses boiled down from the green juice of sorghum grass instead of cane sugar.

She had been nervous when she arrived, but now she was in her element. She needs no timer to know exactly when something should come out of the oven, perfectly brown. She tasted a spoonful of the basil-pistachio pesto. “This is a trip to Sicily,” she said. “Your marriage is struggling, it’s winter, you’ve lost the ability to communicate … and you go to Sicily with your partner. That’s what this is.”

On the other side of the kitchen, Morin was breaking up the fractal patterns of Romanesco broccoli into tiny bits of chartreuse, as a topping for his potato soup. “If he does not taste anything, I also have a bottle of bourbon,” he muttered in Québécois French.

The kitchen began to fill with the smells of bacon and basil, a hint of curry, and the sweetness of cake. The dishes were ready. At the last second, Camerino spooned a glistening white ball of gelato onto the two desserts.

The chefs each came forward to introduce their dish. Then they pulled back toward the kitchen. And with everyone watching, Warner and Radhakrishnan took careful bites, rolling around first the soup and then the cake in their mouths. The chefs looked on, tense, as Warner primly wiped his moustache.

Both tasters complimented the moisture of the cake and the aromas of the soup, the way the spices enlivened the purée, the way the ice cream made it easier to swallow the cake. They would not reveal the winner until the next day, at the end of the conference, in an auditorium full of academics and clinicians.

But a few minutes later, when the room’s attention had moved elsewhere, Radhakrishnan, whose sense of taste has largely come back after two battles with breast cancer, turned to Warner.

“Barry, are you able to taste anything?” she asked, gesturing toward the cake.

There was a pause. Warner looked serious, like he was concentrating on a math problem. “No,” he said quietly.

It might have worked for Warner while he was undergoing chemo and tasting its metallic tang. Or it might have worked for someone else. Just as Warner’s pleasure in food had been shaped in complex ways — by his genes, by the country cooking he’d sampled in the womb and as a child, and then by those foods he’d grown to appreciate as an adult — his preferences were equally unique after he’d lost his sense of taste. After all, a loss is only a loss in relation to what came before.

To Camerino, the challenge was at once amazing and humbling. “I could have cried a lot — I cry really easily,” she said. The experiment only heightened her zeal: She is now working with a molecular sommelier to dream up four different lozenges for people with taste loss, and, for those without saliva, two aromatic sprays. She isn’t sure about the exact ingredients, but she is thinking citrus, basil, barley malt as a sweetener, and something reminiscent of anise.

Han hopes that these events for chefs and scientists can move from “fun preclinical challenges” to more rigorous research about what can actually help these patients and survivors. Morin is working on an app for cancer patients to share what helps for which kinds of taste loss, and there are other ideas in the works. “We’re doing very early studies to take stem cells to see if we could regrow the system,” said Beauchamp, the researcher from the Monell Center. “But we’re a long way from that.”

For now, Warner keeps to the regimen he’s turned to for seven years. He uses whomever he’s eating with as a timer for when he can stop making himself take bites. He smells coffee in the morning, sipping it as he heads into his sunroom to listen for birds. He feels that first burn of bourbon, and notices how it falls away with each subsequent sip.

Print Friendly
December, 2016|Oral Cancer News|

Genetic variants are associated with susceptibility to mouth and throat cancer

Source: www.eurekalert.org
Author: news release

A number of genetic variants associated with susceptibility to oral cavity and pharyngeal cancer have been described in an international study published in the journal Nature Genetics.

The most noteworthy finding was an association between cancer of the oropharynx and certain polymorphisms (alternative versions of a given DNA sequence) found in the human leukocyte antigen (HLA) genomic region. HLAs, proteins found on the surface of most cells in the body, play an important role in recognizing potential threats and triggering the immune response to foreign substances.

According to Eloiza Helena Tajara, a professor at the São José do Rio Preto Medical School (FAMERP) in São Paulo State, Brazil, and co-author of the article, a specific group of variants in this region, located on chromosome 6, is associated with enhanced protection against oropharyngeal cancer caused by human papilloma virus (HPV).

“Previous research showed that these same variants confer protection against cancer of the uterine cervix, which is known to be associated with HPV,” Tajara said. “Our findings suggest that the genes that control the immune system play a key role in predisposition to HPV-related tumors. This discovery points to the possibility of clarifying the mechanisms whereby such tumors develop and of designing methods for monitoring risk groups.”

The study was coordinated by the International Agency for Research on Cancer (IARC) and involved 40 research groups in Europe, the United States, and South America. The Brazilian participants are members of the Head & Neck Genome Project (GENCAPO), a consortium of scientists affiliated with several institutions.

In a recent study, GENCAPO evaluated more than 7 million genetic variants in samples from 6,034 patients with head and neck cancer. The cases comprised 2,990 oral cavity tumors, 2,641 oropharyngeal tumors, 305 tumors in the hypopharynx (the bottom part of the pharynx near the esophagus), and 168 tumors in other regions or more than one region concurrently. The study population also included samples from 6,585 people without cancer as controls.

The researchers detected eight loci (genomic sites) associated with susceptibility to these types of tumor. Seven had not previously been linked to mouth or throat cancer.

According to Tajara, the IARC set out to focus on analyzing oral cavity and oropharynx tumors because there are no genome-wide association studies of these two tumor types. Although these cancers are predominantly caused by tobacco and alcohol use, the importance of HPV, particularly HPV16, as a cause of oropharyngeal cancer has become more evident in recent years.

“The throat is the most affected area among head and neck cancer subsites, likely because its tissue is more receptive to the virus,” Tajara said.

In the article, the researchers note that the proportion of HPV-related oropharyngeal cancer cases is estimated to be approximately 60% in the US and 30% in Europe but lower in South America.

“One finding that was expected to some extent was the absence of HLA associations with oropharyngeal cancer, which may be due to the fact that the frequency of HPV-positive oropharyngeal cancer is less than 10% in South America,” Tajara said. “The same factor appears to account for the weak association between the variants identified and HPV-positive oral cavity cancer, which is also far less frequent than HPV-negative oral cavity cancer.”

In her view, the strong rise in cases linked to HPV in the US could be partly due to a change in sexual habits, especially regarding the practice of oral sex. “It’s possible that Brazil is still in a transition stage and that the habits that favor infection are only starting to become more common. If so, the effects will appear in a few years’ time,” she said.

Previous studies have already shown that HPV-associated head and neck cancers affect younger people and develop rapidly. By contrast, cases associated with tobacco and alcohol use as well as poor oral hygiene are more prevalent in those over fifty years old and progress more slowly but are harder to treat.

In addition to DNA in tissue samples taken from participants of the study, data were also collected on environmental and clinical factors possibly associated with the development of this type of cancer, such as smoking, alcohol consumption, and age.

According to Tajara, thanks to the joint efforts of 40 research groups it was possible to obtain data on a significant number of patients, thus enhancing the impact and reliability of the results. The GENCAPO team contributed some 1,000 samples from tumors for analysis.

“Based on these results, we can try to understand from the molecular standpoint how the observed polymorphisms interfere with the response to HPV infection,” Tajara said. “This may give us clues as to how to protect people and how to reduce the incidence of this type of tumor.”

Print Friendly
December, 2016|Oral Cancer News|

Predicting throat cancer recurrence with a blood test

Source: knowridge.com
Author: from University of Michigan Health System

A new study suggests the possibility of predicting at its earliest stages when a type of head and neck cancer will come back.

Oropharyngeal cancer — which occurs in the throat, tonsils and back of the tongue — is frequently linked to the human papilloma virus. That’s good news, in a way, as HPV-related cancers are generally more responsive to treatment.

But for about 15 to 20 percent of these patients, the treatment won’t work and their cancer will return. There are no known biomarkers to predict when treatments are likely to fail.

In a new study in Clinical Cancer Research, researchers found that patients whose oropharyngeal cancer recurred had higher levels of antibodies for two proteins, E6 and E7, which are found in HPV-fueled cancers. The finding suggests a potential blood-based marker that could predict when cancer is likely to return.

For this study, researchers looked back at 52 patients with advanced oropharyngeal cancer who had enrolled in a prior study: 22 who had developed recurrence and 30 who had not. The two groups were similar in age, cancer classification and smoking status. All tumors were linked to the human papilloma virus.

On average, cancer recurred 13 months after a patient’s treatment ended. Serum was measured via a blood test at diagnosis or start of treatment, then repeated after treatment ended and about every three months after.

Initially, there was no difference in E6 and E7 antibody levels between those patients who recurred and those who didn’t. All patients showed a decline in their antibody levels three months after treatment.

That makes sense, says study author Matthew E. Spector, M.D., assistant professor of otolaryngology at the University of Michigan Health System. After three months, all or most of the cancer had been wiped out. Since oropharyngeal cancer almost never recurs three months after treatment, antibody levels declined in all the patients studied.

“Most patients recur within the first two years, so the window to catch it is two years after treatment. Everyone’s level goes down over time, but some start to go up a little — and those are the ones we have to focus on,” Spector says.

Finding answers in antibodies

When the researchers looked at E6 and E7 antibody levels over time, they found that in patients whose cancer recurred, the levels of E7 were not decreasing as quickly as patients who did not recur. And they could begin to detect that prior to the point when the recurrence was discovered.

“If we can monitor someone through blood markers, then instead of a patient coming for a clinic visit every two to three months, they could get blood drawn near home. If there’s evidence of high E7, we can tell the patient to come in for more evaluation,” Spector says.

The key is to look at the ratio of E7 antibodies. Every patient had a different baseline level, and the absolute level was not an indication.

“It’s very patient-specific,” Spector says. “Each patient will have different levels, but the question is what happens when you track it over time. If it rises, that suggests recurrence.”

Oropharyngeal cancer most commonly recurs in the throat, neck or lungs. If recurrence is caught early, surgery to remove the cancer in the throat or neck can eliminate the disease and is likely to be a cure. If the cancer spreads to the lungs, offering targeted therapies earlier might improve outcomes.

The test for E6 and E7 antibodies is a standard laboratory test that any cancer treatment facility could perform, so it would likely be inexpensive to implement.

More testing among a larger number of patients is needed. The U-M team has opened a phase II trial to assess the potential for E7 antibodies as a biomarker for recurrence. For information, call the U-M Cancer AnswerLine at 800-865-1125.

Print Friendly
December, 2016|Oral Cancer News|

Blood-borne HPV antibodies indicate head, neck cancer prognosis

Source: medicalxpress.com
Author: provided by Brown University

People with head and neck cancers with evidence of human papillomavirus (HPV) infection generally have a better prognosis than people without evidence of infection. A new study in JAMA Oncology suggests that to produce a strong, reliable prognostic signal, all that’s needed is a blood serum test for two specific HPV antibodies, rather than lab work on a biopsy. Further, the researchers said, the study shows that this blood-based biomarker is predictive of outcome for all types of head and neck cancer.

bloodbornehp

The human papillomavirus causes not only cervical cancer but also cancers of the head and neck. Credit: National Cancer Institute

“What this adds is that it helps us know how best to measure clinically the HPV contribution to this disease,” said study senior author Karl Kelsey, a professor of epidemiology and of pathology and laboratory medicine at Brown University. Kelsey collaborated with lead author Heather Nelson of the University of Minnesota Masonic Cancer Center in making the findings.

Moreover, Nelson, Kelsey and their colleagues wrote, referring to the common HPV16 strain of the virus: “These data are among the first to demonstrate a convincing relationship between HPV16 and improved patient survival for tumors of the larynx and oral cavity.”

Appraising antibodies
The study examined blood serum samples and five-year survival rates among more than 1,000 Boston-area head and neck cancer patients diagnosed between 1999 and 2011. Overall, those who tested positive for antibodies to the oncogenic HPV proteins E6 or E7 were less likely to die during the five year follow-up period after diagnosis compared to those who tested negative for the antibodies. Based on the analysis, the researchers estimated that those with evidence of an immune response to HPV were 25% less likely to die during the course of follow-up compared to those with no immune response to HPV.

The study’s purpose was to determine whether the antibodies provide a reliable indication of prognosis. In ongoing trials, doctors are testing whether patients with HPV-associated cancers can be treated less aggressively—and hopefully with fewer negative side effects—than people with non-HPV-associated cancers, Kelsey said. If trials prove successful, then it will be particularly important to determine whether cancers are HPV-associated.

“The assessment of a patient’s HPV status likely will affect treatment,” he said. “That’s why there’s real interest in getting it right; for instance, how do you test?”

Better prognosis across the board
Prior studies have focused primarily on the role of HPV in the oropharynx—the area of the throat right behind the mouth. An important contribution of the current study, Nelson said, is demonstration that an immune response to HPV is important for all forms of head and neck cancer, although the benefit does show some variance based on the exact cancer location. Those patients with an HPV immune response with tumors located in the oropharynx and larynx had a similar risk of dying during the follow-up period, though the reduced risk was slightly attenuated for those patients with tumors located in the oral cavity.

The results didn’t depend significantly on whether people had high or low levels of the antibodies, so long as they had some, the researchers found, though testing positive for both E6 and E7 was better than for just one.

The reduced chance of dying by five years carried through for people who tested positive for the antibodies even if they consumed tobacco and alcohol. But the worst prognoses in the study were among smokers whose cancers could not be traced to HPV.

In all, the findings controlled for the statistical influences not only of tobacco and alcohol exposure, but also of age, race, gender, education and how far advanced the cancer was.

Relates to broader advances
Kelsey said the findings could help bring head and neck cancer treatment closer into line with two emerging practices of fighting the disease: personalized medicine and immunotherapy.

“To me, personalized medicine really reflects using all the information you can glean about an individual tumor to treat it appropriately,” Kelsey said. “Here HPV is an example of a causal factor that delineates the mechanism of the tumor suppressor genes that drive the tumor and that gives you insight into the differences in the tumor.”

Meanwhile, the study might help shed light on why immunotherapy—in which the body’s immune system is marshaled to attack cancer—appears to help for some head and neck cancers, Kelsey said. It may not be coincidence, for instance, that the prognosis is better among people whose cancers are associated with a virus that promotes a robust immune response, in the form of antibodies, than among people without a viral cause for their cancer.

If HPV-related cancers can indeed be treated differently, Kelsey said, then serum-based testing to determine the role of the virus could soon be available, too.

Print Friendly
December, 2016|Oral Cancer News|

US Surgeon General Says Vaping Among Young People is a ‘Major Public Health Concern’

Report calls for higher taxes and stronger regulations on the e-cigarette industry

Author: Amar Toor

Source: http: www.theverge.com

The US surgeon general says that the increased use of e-cigarettes among young people represents a “major public health concern,” The Washington Post reports, and is calling on lawmakers to implement regulations that would curb their use among American youth. In a report to be released on Thursday, Surgeon General Vivek Murthy says that although there is a need for further research on the long-term effects of e-cigarettes, exposure to nicotine through vaping poses serious health risks to young people.

“We know enough right now to say that youth and young adults should not be using e-cigarettes or any other tobacco product, for that matter,” Murthy said in an interview with the Post. “The key bottom line here is that the science tells us the use of nicotine-containing products by youth, including e-cigarettes, is unsafe.”

“Young adults should not be using e-cigarettes or any other tobacco product.”

The report, which focuses on vaping among young people, acknowledges that e-cigarettes are less harmful than traditional cigarettes, as previous research has shown. But the surgeon general says there is not strong evidence that the devices are effective at helping people to quit smoking cigarettes, and concludes that vaping is “strongly associated” to the use of other tobacco products. A report from the Centers for Disease Control and Prevention (CDC) found that 3 million American teenagers used e-cigarettes in 2015, marking a ten-fold increase over four years.

The surgeon general’s warnings contrast with a report published earlier this year by the Royal College of Physicians in the UK, which said that e-cigarette use should be encouraged as a healthier substitute for tobacco cigarettes. That report, released in April, concluded that e-cigarette use in the UK is “limited almost entirely to those who are already using, or have used, tobacco,” and said that the products can be seen “as a gateway from smoking.” The long-term effects of e-cigarette use remain unclear, though a study released in July identified two cancer-causing chemicals in the vapor that the products release.

The US Food and Drug Administration (FDA) banned the sale of e-cigarettes to people under 18 earlier this year, and now require manufacturers to submit their ingredients for approval. The surgeon general’s report recommends stronger regulations, including a sales ban for people under the age of 21, higher taxes, and restrictions on marketing that targets young people.

 

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

Print Friendly
December, 2016|Oral Cancer News|

I get by with help from my friends: Maintaining immune cells in head and neck cancer

Source: www.eurekalert.org
Author: Medical University of South Carolina

In an article published September 22, 2016 in Frontiers in Immunology, researchers at the Medical University of South Carolina (MUSC) and the Ralph H. Johnson VA Medical Center report that inhibiting prostaglandin production slows the progression of premalignant lesions to head and neck squamous cell carcinoma (HNSCC). Preclinical studies showed that treatment of premalignant lesions with indomethacin, a nonsteroidal anti-inflammatory drug (NSAID) similar to aspirin, increased the presence of immune cells and lessened tumor burden.

Cancers of the head and neck begin with lesions in the oral cavity, including the larynx, pharynx, throat, lips, mouth, salivary glands, and nasal passages. Although the incidence of HNSCC has been on the decline over the past several decades, the National Cancer Institute reports that approximately 3% of all cancers in the U.S. result from HNSCC, with men being diagnosed twice as often as women. Treatment for HNSCC includes surgical removal and chemo-radiation treatment; however, these interventions often fail, and patients have a five-year survival rate of only 50%. It is critical to determine better treatment options for HNSCC patients.

One way researchers at MUSC are trying to improve the treatment of HNSCC is by enhancing the body’s own immune system to attack the tumor.

“There’s a lot of effort to stimulate immune reactivity using immunotherapy. The problem with that is cancer can protect itself against the immune defenses. Head and neck cancer is notorious for that,” said immunologist M. Rita Young, Ph.D., senior author for this study, who holds a dual appointment at MUSC and the Ralph H. Johnson VA Medical Center.

As an immunologist, Young has been working on addressing this problem by studying how the immune system affects tumor progression. Previous work from her laboratory has shown that the composition of immune cells within premalignant lesions differs from that within HNSCC. Significantly, as premalignant cells develop into HNSCC, the immune environment switches from stimulatory/inflammatory to immunosuppressive. This change in the tumor microenvironment prevents the immune system from combating the cancer. Prostaglandin may be an important mediator of this switch.

The current study used a novel mouse model of HNSCC to determine how inhibition of prostaglandin affects tumor progression. Mice with premalignant lesions were given indomethacin, an NSAID that inhibits the production of prostaglandin. Indomethacin treatment increased the presence of immune cells at the lesion site and led to a systemic activation of the immune system. Specifically, there was an increase in both Th1-associated cytokines (IL-2 and IFN-γ) as well as Th2-associated cytokines (IL-10). This activation of the immune system reduced the progression of premalignant lesions to HNSCC.

Future studies in this area will be focused on maintaining a strong immune presence in pre-malignant lesions for patients. If studies in humans bear out these preclinical findings, further research using more specific prostaglandin inhibitors in combination with other immunomodulatory compounds could provide a better treatment regimen to prevent the formation of HNSCC.

“Immunotherapy should be considered as a treatment strategy for premalignant lesions before they progress to cancer. We can detect them. Why not treat them?” said Young. Furthermore, these intervention strategies may be able to help prevent smaller, as yet undetectable lesions from progressing to HNSCC.

This work provides strong evidence that treatment of premalignant lesions with indomethacin reduces the tumorigenicity of HNSCC. A better understanding of the mechanisms by which the immune system combats early-stage cancer could lead to improved clinical outcomes in HNSCC, and potentially, other types of cancer as well.

“If we can be more persistent and focused on finding premalignant lesions before they become malignant, simple therapies might be beneficial,” said Sara Johnson, Ph.D., a postdoctoral fellow at MUSC and a co-author on the article.

Print Friendly
December, 2016|Oral Cancer News|

Bioscientists help throat cancer patients speak again

Source: medicalxpress.com
Author: staff, provided by the University of Kent

bioscientist

Voice Prosthesis Biofilm. Credit: Dr Campbell W. Gourlay, University of Kent

Through the work of the School of Biosciences team, in collaboration with East Kent Hospitals University NHS Foundation Trust, Kent has developed a new method of care for patients who have to have their larynx removed.

The Biosciences team found that the replacement voice boxes would last much longer if they dealt with the fungal infection Candida albicans that was causing the silicone versions to fail. For the first time, scientists were able to extend the life of the replacement voicebox by dealing with the fungal infection.

The team has developed clinical care for patients that has now been taken up by many NHS Trusts in the UK and which is anticipated could be used worldwide for throat cancer patients.

It means patients may be able to carry on using silicone voice prosthesis for much longer, enabling them to still speak and reducing the risk of dangerous secondary chest infections.

Dr Campbell Gourlay, Senior Lecturer in Cell Biology at Kent, said the University’s work, funded by the NHS and Kent Cancer Trust, will enable people who lose their larynx to maintain speech and enjoy a better quality of life.

Print Friendly
December, 2016|Oral Cancer News|

Mouth cancer rates soar over 20 years

Source: www.sciencedaily.com
Author: staff

A new Cancer Research UK analysis reveals that rates of mouth (oral) cancer have jumped by 68 per cent1 in the UK over the last 20 years. The figures — released during Mouth Cancer Action Month — reveal the cancer is on the rise for men and women, young and old, climbing from eight to 13 cases per 100,000 people over the last two decades.

For men under 50, the rate has jumped by 67 per cent in the last 20 years2 — going up from around 340 cases to around 640 cases each year. For men aged 50 and over, rates have increased by 59 per cent climbing from around 2,100 cases to around 4,400 cases annually.

Oral cancer is more common in men, but there have been similar increases women3.

In women under 50, oral cancer rates have risen by 71 per cent in the last 20 years, with annual cases climbing from around 160 to around 300. Rates for women over 50 have also gone up by 71 per cent, with cases increasing from around 1,100 to around 2,200.

Around nine in 10 cases are linked to lifestyle and other risk factors. Smoking is the biggest avoidable risk factor, linked to an estimated 65 per cent of cases. Other risk factors include alcohol, diets low in fruit and vegetables, and infections with the Human Papilloma Virus (HPV).

Oral cancers include cancer of the lips, tongue, mouth (gums and palate), tonsils and the middle part of the throat (oropharynx)4.

Cancer Research UK — working with the British Dental Association — has developed an oral cancer toolkit5 to help GPs, dentists, nurses and hygienists spot the disease and refer suspected cases sooner.

Jessica Kirby, Cancer Research UK’s senior health information manager, said: “It’s worrying that oral cancer has become more common. It’s important to get to know your body and what’s normal for you, to help spot the disease as early as possible. An ulcer or sore in your mouth or tongue that won’t go away, a lump on your lip or in your mouth, a red or red and white patch in your mouth or an unexplained lump in your neck are all things to look out for. Speak to your GP or dentist about any changes that are unusual or don’t go away.

“Healthy lifestyles can help reduce the risk of developing the disease in the first place. Not smoking, drinking less alcohol and eating plenty of fruit and vegetables can all help to cut our risk of mouth cancer. HPV vaccination could help protect against oral HPV infections, and it can prevent a range of cancers associated with the HPV virus, so it’s a good idea to get the vaccine if you are offered it.”

With smoking being the biggest preventable cause of oral cancer, Cancer Research UK is also calling on the public and local councillors to help protect vital Stop Smoking Services. These specialist services are the most successful way for people to quit smoking.

Andrea Fearon, 47 from Newbury, was diagnosed in 2013 with mouth cancer after a routine checkup by her dentist.

Andrea said: “I had thought that most people with mouth cancer are heavy smokers over the age of 50, so I completely shocked when I was diagnosed with the disease. I’m proof that this type of cancer isn’t limited to a particular age or sex. I thought seeing the dentist was about looking after your teeth — but it can save your life. It’s thanks to my dentist that the mouth cancer was caught early — that’s why I feel so lucky to be alive.”

Notes:
1. Based on oral cancer incidence rates for all ages, persons, from 8 cases per 100,000 people between 1993-1995 to 13 cases per 100,000 people between 2012-2014.

2. Based on oral cancer incidence rates, for males aged 0-49, the rise is from two cases per 100,000 males between 1993-1995 to three cases per 100,000 males between 2012-2014. For men aged 50 and over, this rise is from 26 cases per 100,000 between 1993-1995 to 41 cases per 100,000 men between 2012-2014.

3. Based on oral cancer incidence rates, for females aged 0-49 years, the rise is from one case per 100,000 females between 1993-1995 to two cases per 100,000 females between 2012-2014.

For women aged 50 and over, the rise is from 11 cases per 100,000 women between 1993-1995 to 18 cases per 100,000 women between 2012-2014.

Cases are based on the number of new diagnoses between 1993-1995 and between 2012-2014.

4. Oral cancer includes ICD-10 C00-C06, C09-C10 and C12-C14 (which include the lip, tongue, mouth, oropharynx, piriform sinus, hypopharynx and other and ill-defined sites of the lip, oral cavity and pharynx).

For the latest oral cancer statistics visit the Cancer Research UK statistics webpage http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/oral-cancer

5. The toolkit covers the signs to look out for, how to respond, as well as possible risk factors for oral cancer. The toolkit also features a detailed image library, a referral guide, case studies, examination videos and a CPD accredited quiz.

Story Source:
Materials provided by Cancer Research UK. Note: Content may be edited for style and length.

Print Friendly
November, 2016|Oral Cancer News|

Why the FDA Wants More Control over Some Lab Tests

The FDA finds that many so-called laboratory-derived tests may actually harm patients

By Charles Schmidt | Scientific American December 2016 Issue

Every year in the U.S., doctor’s offices and hospitals order billions of laboratory tests to measure everything from cholesterol levels in the blood to the presence of a gene thought to increase the risk of developing Alzheimer’s disease. Physicians and patients typically assume that they can trust the results of these tests. And most of the time they can. But not all lab tests are equally reliable, and faulty ones can have serious consequences. Sometimes they fail to detect life-threatening conditions. Other times they indicate a problem that does not exist, which can lead to unneeded, perhaps even dangerous treatments.

Through a quirk of regulatory history, many such tests are not subject to the same medical standards as other tools used to identify risk for disease or to definitively diagnose a condition. These are called lab-developed tests, or LDTs, defined as tests that are manufactured and interpreted by the same individual lab that designed them—in contrast to, say, a quick strep test meant to be used and understood by a wide variety of personnel in doctor’s offices everywhere. Most people first encounter an LDT during a checkup when the physician is faced with a diagnostic dilemma that cannot be resolved by widely available blood tests.

The trouble is, experts believe many of these tests are not useful, and some may even cause harm by convincing too many people that they have a rare illness when they do not, diagnosing them with a condition that has so far not been shown to be harmful or reassuring them that they are healthy when in fact there is no scientifically credible way to know if that is indeed the case. “We tend to think of lab tests as being the ultimate truth,” says Ramy Arnaout, an assistant professor of pathology at Harvard Medical School. “But no test is 100 percent accurate, and some of these LDTs aren’t medically useful at all.”

The U.S. Food and Drug Administration is now taking steps to restore confidence in the reliability of lab-developed tests. In 2014 the agency released proposed guidelines that will subject the measures, for the first time, to federal oversight—including having to submit evidence of efficacy to it before the tests may be marketed. Although the FDA would not comment for this story, several industry sources believe the final rulings may begin taking effect soon, much to the chagrin of some lab directors who say that the requirements could boost costs and hinder medical practice.

Widening Loophole

Twenty-five years ago LDTs played too small a role in medical practice for the FDA to pay them much attention. Only a few—most notably Pap smears for the detection of cervical cancer—were widely used. FDA officials adopted a policy of “enforcement discretion,” which meant they pretty much left LDTs alone while they focused on tools with an apparently greater potential for harm, such as malfunctioning pacemakers.

After researchers developed new genetic engineering techniques in the 1990s, however, the possibilities for LDTs expanded dramatically. Whereas previous generations of LDTs looked for a handful of unusual proteins, for example, some of the newly emerging genetic tests could sort through any number of the three billion base pairs, or letters, of the DNA alphabet found in the human genome, looking for abnormalities related to disease. In addition, testing became automated, making LDTs increasingly easier to design and use.

The improved technology led to an enormous rise in the number and variety of LDTs that came to market. By some estimates, about 11,000 labs now offer between 60,000 and 100,000 of them; no one knows precisely how many because, of course, these tests do not have to be registered anywhere.

Under current federal regulations, LDTs enjoy a big loophole, which means they do not have to be evaluated for their medical usefulness. Nor are they required to have research about them made public. The lab that created them does need to meet certain fundamental standards of scientific practice. But the FDA does not vet the tests either before or after doctors can start ordering them for patients, as it does for most prescription drugs or medical devices.

This loophole means that companies ranging from small start-ups offering just one or two tests to much larger diagnostic labs that offer thousands of tests can develop and charge for new LDTs much more easily than they can for most other categories of medical products. With the rise in the number of tests has come a series of reports showing that certain ones have already hurt people by delivering misleading results.

Clinical Validity

The FDA has cited 20 different types of LDTs as especially troubling, including Lyme disease and whooping cough tests that regularly give wrong answers and LDTs that purport to determine a woman’s risk for ovarian cancer such as by measuring the presence of the protein CA 125 in the blood. In September the agency concluded that screening measures for this protein offered “no proven benefit” and warned physicians against recommending or using them.

Many of the tests that have raised the FDA’s ire may indeed measure what they claim to measure. The problem is that the measured substance may not be a good indicator of a specific medical problem. In the case of the ovarian cancer tests, for instance, high levels of CA 125, which is made in the ovaries, should in theory signify the presence of extra ovarian cells—in other words, the presence of a tumor. In reality, it turns out that many women with high levels of CA 125 do not have ovarian cancer, and, conversely, many women with cancer do not have high levels of CA 125. Thus, measures of CA 125 cannot be trusted to give an accurate diagnosis of cancer—and yet a number of women who tested positive apparently feared the possibility of cancer so much that they decided to have their healthy ovaries removed anyway.

One way that investigators determine whether a medical test should be used as a guide to a patient’s condition is by applying a somewhat obscure statistical ratio called a positive predictive value, or PPV. This measure takes into account just how common a condition might be in a given group of people.

Why such a consideration would be important in determining a test’s usefulness may be best understood by analogy. If you drop a baited hook into a barrel full of fish, the chances that a tug on the line means that you have caught a fish are pretty high. On the other hand, dropping the same baited hook into a freshwater lake that has not been stocked with fish makes it much less likely that any given tug on the line represents a fish, as opposed to, say, a tree snag. Because the barrel contains many more fish for a given volume of water than the lake does, a tug in the container has a PPV close to 100 percent, whereas that of a tug in an unstocked lake is much less than 100 percent.

This crucial statistical distinction explains the problem the FDA has with one current ovarian screening test, which its developer claimed had a PPV of 99.3 percent. Closer analysis by independent biostatisticians revealed, however, that the value was calculated on the basis of a single experiment in which half the patients were already known to have ovarian cancer—a highly selected group that is the medical equivalent of a stocked pond.

When the researchers recalculated the PPV using ovarian cancer’s true frequency in the general U.S. population of one case for every 2,500 postmenopausal women, the PPV plummeted to just 6.5 percent. In other words, only one in every 15 patients who received a positive result from this malignancy test would have actually had ovarian cancer. The other 14 would, if they had relied on this test alone, very likely have undergone unnecessary operations to remove their otherwise healthy ovaries because they would have mistakenly believed they had a 99.3 percent chance of having cancer.

Changing Focus

Because the FDA does not have the resources to oversee all the LDTs that have come to market in recent years, the agency plans to divide them into three categories, based on the likelihood that a misleading or incorrect result from a particular test could cause substantial harm. Under the new guidelines, LDTs would be considered high risk if inaccurate results could lead to death or prolonged disabilities. Such tests would come under the greatest inspection, information about them would need to be entered in a national database, and manufacturers would have to prove their safety and efficacy to the FDA before they could be sold. “Basically, the FDA wants to see the supporting evidence before it allows a high-risk LDT to go out on the market,” says Joshua Sharfstein, a physician and professor at the Johns Hopkins Bloomberg School of Public Health.

Even this targeted approach worries many industry leaders and some professional medical societies, including the American Medical Association. “It really depends on how the FDA chooses to define high risk, and that currently isn’t clear,” says Curtis Hanson, chief medical officer at Mayo Medical Laboratories in Rochester, Minn., which conducts 25 million lab tests a year. “High-risk tests could amount to between 1 and 10 percent of LDTs on the market today. How is the FDA going to review and find the rare cases where you have problems and do that in an efficient way that doesn’t slow progress?”

For patients and their physicians, the question is much more basic. Why should they ever have to wonder whether a commercially available medical test does more harm than good?

This article was originally published with the title “When Medical Tests Mislead”

 

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

Print Friendly
November, 2016|Oral Cancer News|

For this cancer, ‘stage 4’ isn’t as bad as it sounds

Source: www.omaha.com
Author: Steve Hendrix – The Washington Post

Hearing the word “cancer” in a doctor’s office is bad enough. Hearing “stage 4” invokes even more dread. When I learned I had stage 4 HPV-related oral cancer, I didn’t know exactly what it meant, but I knew there wasn’t a stage 5.

Doctors use the standardized staging system to describe the location, size and extent of a cancer and its spread throughout the body. Using data on the treatment and survivability of each particular kind of cancer, clinicians combine these factors to produce a number from stage 1 (a small tumor confined to one spot) to stage 4 (a cancer that has spread, either to a single adjacent lymph node or to distant organs).

My cancer was stage 4A, a small tumor at the base of my tongue that had spread to a single lymph node in my neck.

My doctor immediately tried to soften the blow. There were problems with the staging rules as they applied to this kind of cancer, he said. HPV oropharyngeal cancers, while potentially fatal, were far more treatable than other oral cancers, particularly the ones related to tobacco and alcohol use that were used to define the staging standards.

He was right. A study published in the Lancet early this year found that the current guidelines lead to needless panic for the newly diagnosed. “At the present time, most patients with HPV+ oropharyngeal cancer are told they have (stage 4) disease, but the reality is that their outlook is similar to that of patients with the most curable malignant diseases,” the study authors wrote.

This month, the American Joint Committee on Cancer is releasing new guidelines for HPV-positive oropharyngeal cancer staging that will ease patient fears and make it easier for doctors to offer less-invasive treatment options.

“It’s remarkable,” said my own physician, Arjun Joshi of George Washington University. “Under the new system, you would only be a stage 1.”

Print Friendly
November, 2016|Oral Cancer News|