Monthly Archives: May 2019

Queensland scientist develops new HPV cancer vaccine

Source: 9News
Date: May 22, 2019
Author: 9News Staff

*click Source to view video*

Former Australian of the Year Professor Ian Frazer has developed a vaccine aimed at treating HPV-related cancers of the head, neck, throat and tongue.

While funding is still being finalised, a trial of the vaccine is being prepared for people with incurable oropharyngeal cancers.

Professor Frazer, the Scottish-born immunologist who developed and patented the vaccine against HPV-related cervical cancer, has been working on this vaccine for nearly 15 years.

While the cervical cancer vaccine works as a preventative, this new vaccine is a treatment therapy.

It works by teaching the patient’s immune system to target the cancer cells containing HPV. The patient will then be given immunotherapy drugs that supercharge the immune system.

“This is all about a new way to treat cancer using the body’s defence against infection,” Professor Frazer said.

“This might give a second chance at life.”

HPV-related throat cancer kills three Australians every day.

“It’s going to become a major problem in Australia, in fact in the US we’ve seen an increase in HPV-related throat cancers by 225 per cent,” head and neck radiation oncologist Sandro Porceddu said.

Professor Porceddu will conduct the trial at the Princess Alexandra Hospital. It should begin towards the end of this year if a further $700,000 in necessary funding is found.

© Nine Digital Pty Ltd 2019
May, 2019|Oral Cancer News|

Greens and Genes

Source: Harvard Medical School
Date: May 16, 2019
Author: Jacqueline Mitchell

Your mother was right: Broccoli is good for you.

Long associated with decreased risk of cancer, broccoli and other cruciferous vegetables—the family of plants that also includes cauliflower, cabbage, collard greens, Brussels sprouts and kale—have now been found to contain a molecule that inactivates a gene known to play a role in a variety of common human cancers.

In a new paper published May 16 in Science, researchers led by Pier Paolo Pandolfi, the HMS Victor J. Aresty Professor of Medicine at Beth Israel Deaconess Medical Center, demonstrate that targeting the gene, known as WWP1, with the ingredient found in broccoli suppressed tumor growth in cancer-prone lab animals.

“We found a new important player that drives a pathway critical to the development of cancer, an enzyme that can be inhibited with a natural compound found in broccoli and other cruciferous vegetables,” said Pandolfi, who is also director of the Cancer Center and Cancer Research Institute at Beth Israel Deaconess.

“This pathway emerges not only as a regulator for tumor growth control, but also as an Achilles’ heel we can target with therapeutic options,” Pandolfi said.

One of the most frequently mutated, deleted, downregulated or silenced tumor suppressor genes in human cancersis PTEN. Certain inherited PTEN mutations can cause syndromes characterized by cancer susceptibility and developmental defects.

Because complete loss of the gene triggers an irreversible and potent failsafe mechanism that halts proliferation of cancer cells, it’s rare for both copies of the gene (humans have one copy from each parent) to be affected. Instead, tumor cells exhibit lower levels of PTEN. This raises the question of whether restoring PTEN activity to normal levels in the cancer setting can unleash the gene’s tumor-suppressive activity.

To find out, Pandolfi and colleagues identified the molecules and compounds regulating PTEN function and activation.

Carrying out a series of experiments in cancer-prone mice and human cells, the team revealed that a gene called WWP1, which is also known to play a role in the development of cancer, produces an enzyme that inhibits PTEN’s tumor-suppressive activity.

How to disable this PTEN kryptonite?

By analyzing the enzyme’s physical shape, the research team’s chemists recognized that a small molecule—formally named indole-3-carbinol (I3C), an ingredient in broccoli and its relatives—could be the key to quelling the cancer-causing effects of WWP1.

When Pandolfi and colleagues tested this idea by administering I3C to cancer-prone lab animals, they found that it inactivated WWP1, releasing the brakes on PTEN’s tumor-suppressive power.

But don’t head to the farmer’s market just yet. First author Yu-Ru Lee, HMS research fellow in medicine and a member of the Pandolfi lab, notes you’d have to eat nearly six pounds of Brussels sprouts a day, and uncooked ones at that, to reap their potential anti-cancer benefit.

That’s why the Pandolfi team is seeking other ways to leverage this new knowledge. The team plans to further study the function of WWP1 with the ultimate goal of developing more potent, and practical, WWP1 inhibitors.

Genetic or pharmacological inactivation of WWP1 with either CRISPR technology or I3C could “restore PTEN function and further unleash its tumor suppressive activity,” said Pandolfi. “These findings pave the way toward a long-sought tumor suppressor reactivation approach to cancer treatment.”

This work was mainly supported by the National Institutes of Health (grants R01CA82328 and R35CA197529).

In addition to Pandolfi and Lee, authors include Ming Chen, Jonathan D. Lee, Jinfang Zhang, Tomoki Ishikawa, Jesse M. Katon, Yang Zhang, Yulia V. Shulga, Assaf C. Bester, Jacqueline Fung, Emanuele Monteleone, Lixin Wan, John G. Clohessy, and Wenyi Wei, all of Beth Israel Deaconess; Shu-Yu Lin, Shang-Yin Chiang and Ruey-Hwa Chen of the Institute of Biological Chemistry; Tian-Min Fu and Chen Shen of Harvard Medical School; Chih-Hung Hsu, Hao Chen and Hao Wu of Boston Children’s Hospital; Antonella Papa of Monash University; Julie Teruya-Feldstein of Icahn School of Medicine at Mount Sinai; Suresh Jain of Intonation Research Laboratories; and Lydia Matesic of the University of South Carolina.

Disclosures: Pandolfi, Wei and Jain are cofounders of Rekindle Pharmaceuticals, which is developing novel therapies for cancer. All other authors declare no competing interests.

May, 2019|Oral Cancer News|

The Problem With Supplements

Source: Elemental
Date: May 6, 2019
Author: Markham Heid

Earlier this year, federal authorities announced plans to strengthen oversight of the supplement industry.

“The growth in the number of adulterated and misbranded products — including those spiked with drug ingredients not declared on their labels, misleading claims, and other risks — creates new potential dangers,” said U.S. Food and Drug Administration (FDA) commissioner Dr. Scott Gottlieb in a February press release.

Heightened oversight is needed, Gottlieb argued, because expansion and change within the supplement industry has made it difficult for his agency to keep pace. “What was once a $4 billion industry comprised of about 4,000 unique products, is now an industry worth more than $40 billion, with more than 50,000 — and possibly as many as 80,000 or even more — different products available to consumers,” he said.

From multivitamins and botanicals to probiotics and protein powders, roughly three out of four Americans now take some kind of supplement on a regular basis. Since the days of palliative tonics and snake-oil salesmen, Americans have been readily lured by the promise of health or longevity in the form of a drink, pill, or powder. While the terminology has evolved — “biohacking” and “nutraceuticals” are some of the buzzwords du jour — the implied benefits of most supplements still outpace or ignore the science. And despite recent studies that find supplements are frequently contaminated or that the best way to get nutrients is through food, Americans’ interest in supplements is only growing. And experts say many supplement users don’t recognize or appreciate the risks that accompany the use of these products.

“Pill use among every age group is at an all-time high,” says Dr. Mark Moyad, the Jenkins/Pomkempner director of preventive and alternative medicine at the University of Michigan. “There isn’t a medical condition or symptom you can name that doesn’t have a supplement you can take to treat or prevent it.”

“There’s a huge disconnect between people’s perception of supplements and the reality, and that can be really destructive.”

In some respects, the growth of the supplement industry is a good thing. As America’s population has grown older, fatter, and sicker, Moyad says there’s potential for targeted supplement use to fill in some nutrient shortfalls caused by unhealthy eating habits or disease-related deficiencies. There’s also little doubt that some groups — notably pregnant women and older adults — can benefit from taking certain supplements, he says.

“But the idea that you can take 10 pills a day and fix everything or live forever is faulty,” he says. “There’s a huge disconnect between people’s perception of supplements and the reality, and that can be really destructive.”

“Most supplements on the market are not tested for either efficacy or safety,” says Dr. JoAnn Manson, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston. She mentions heavy metal contamination and other concerns related to poor manufacturing practices, and compares the current regulatory environment to “the Wild West.” Just last year, a JAMA report found unapproved pharmaceutical ingredients have turned up in hundreds of products.

If you’re taking a handful of supplements without a doctor’s oversight, she says, “there’s the potential for almost anything to happen.”

In the mid-1980s, researchers at Seattle’s Fred Hutchinson Cancer Research Center, and elsewhere, were optimistic about the disease-fighting potential of antioxidants and vitamins.

Two in particular — beta-carotene and vitamin A — had shown promise in early dietary studies. “Beta-carotene is an antioxidant and a natural component of green and orange-yellow vegetables,” says Dr. Gilbert Omenn, who back then was at Fred Hutchinson and is now a professor of human genetics and molecular medicine at the University of Michigan. “Vitamin A was shown to reduce cell division and the proliferation of cancer cells.”

After gaining study approval from the National Cancer Institute, Omenn and his colleagues recruited more than 18,000 men and women who were at high risk for lung cancer. They randomly divided these volunteers into two groups; one took a placebo while the other swallowed a daily supplement containing 30 mg of beta-carotene and 25,000 IU of vitamin A.

Omenn says the goal of his government-funded study, which was known as CARET, was to lower cancer incidence. “We had beta-carotene for its antioxidant properties and vitamin A for its antiproliferative effect, and we thought it would be a nice combination,” he says.

The results of CARET were so disastrous that the trial had to be terminated almost two years early. Rather than lowering rates of lung cancer, the supplement had the opposite effect. Among the people taking it, “we saw one additional cancer case per thousand people,” Omenn says. That may not sound like a lot, but in the world of cancer statistics, an increase of one case per 100,000 people is significant.

“What we observed was maybe the most potent carcinogenic effect ever discovered,” he says. “It was truly shocking.”

What went wrong? It turns out that, when confronted with an overabundance of certain antioxidants, the human body may convert them into prooxidants, which have the potential to activate cancer pathways. “Something fundamental we didn’t understand in advance was that, in living systems, antioxidants are not antioxidants in all situations,” Omenn says.

Troublingly, another group of researchers more or less replicated Omenn and his team’s work in a later trial that looked at the effect of vitamin E and selenium supplements on prostate cancer incidence. Again, people at high risk for cancer were randomly assigned either a placebo or a daily supplement. And again, the study had to be ended early because cancer rates soared.

The lesson here isn’t that supplements give people cancer. Rather, it’s that approaching supplements as though they’re all upside is a misguided and potentially harmful operating philosophy. When you swallow a capsule packed with concentrated amounts of a vitamin, nutrient, or other substance — a practice that did not become widespread until very recently — you can get into trouble. “To this day, there remain people who believe vitamins and organic compounds are inherently safe and that our studies were flawed,” Omenn says. “But clearly, that’s not true.”

Omenn says that heavy doses of vitamin A can also promote bone pain or swelling, headaches, and skin problems among adults. Taken during pregnancy, large doses of vitamin A can cause birth defects, he says.

While individual supplements are unlikely to pack dangerous levels of vitamin A, people who take multiple supplements with overlapping ingredients may be playing with fire. “I see patients who come in with a whole bag of supplements they’re taking — an immune booster, something for hair, something for vision, something for skin — but if you look at the ingredients, you see they’re all the same,” says Dr. Zhaoping Li, a professor of medicine and director of clinical nutrition at UCLA Medical Center. “So someone is taking three or four things with vitamin A, and also a multivitamin with vitamin A, and all these can add up.”

Li explains that fat-soluble vitamins can accumulate in the body and cause liver toxicity. She says that, on rare occasions, she’s seen patients who needed liver transplants due to supplement overuse. But a more typical reaction to this sort of nutrient overdose could be elevated levels of inflammation accompanied by GI side effects like nausea and bloating, she says. “But these are nonspecific symptoms,” she adds, meaning doctors who see people with these issues probably wouldn’t associate them with supplement overuse.

While specifics vary from one product to the next, nearly all supplements come with some level of risk — including some of the most popular pills on the market today.

“When you talk about fish oil and omega-3, it’s very difficult and expensive to preserve the goodness of the fatty acids and to put it in capsules,” says Chandan Sen, associate vice president of research at the Indiana University School of Medicine. If fish oil is not properly preserved, he says, it becomes oxidized and potentially harmful. Taking such a product has “a similar impact on the body as taking over-fried cooking oil,” he explains.

Sen has written extensively on the risk and role of supplements. He says heavy-metal contamination is a common and well-documented issue associated with herbal products. He, and others, also point out that, time and again, research has shown that taking concentrated doses of food-derived or plant-derived nutrients does not confer the same benefits as eating the foods or plants themselves.

“In the cancer world, we tell people to avoid processed foods, and supplements by definition are processed foods.”

“It’s often harder for the body to metabolize an isolated vitamin or nutrient on its own,” says Lorenzo Cohen, a distinguished professor and director of the Integrative Medicine Program at the University of Texas MD Anderson Cancer Center in Houston. Cohen says that whole, unprocessed foods contain “a whole pharmacology” of different compounds and chemicals that together have a synergistic effect not found when those same chemicals are isolated and taken as supplements. It’s this synergy, he says, that seems to provide the greatest health benefit and the least amount of risk.

“Take curcumin, which is popular in the cancer world,” he says. Curcumin is found in turmeric root, and some research has found that it has antioxidant and anti-inflammatory properties. “When you consume curcumin as ground up turmeric powder and use it in cooking, you’re getting it with this rich soup of different phytochemicals and other constituents that are probably helpful,” he explains. On the other hand, taking concentrated curcumin in a capsule — even if its paired with other ingredients to boost its bioavailability — doesn’t seem to have the same effect, and it may come with risks, he says.

“In the cancer world, we tell people to avoid processed foods, and supplements by definition are processed foods,” he adds.

Sen echoes many of these warnings. “There’s evidence that berry anthocyanins may have potent anticancer chemopreventive effects,” he says. “But these anthocyanins have a very specific chemical structure.” When supplement makers try to extract these structures and put them into pills or powder, they often end up with a very different structure, he explains.

Sen says he’s interacted with many supplement companies. And his experience, by and large, has been that most of them spend far, far more of their budget on product marketing than on proper research and development. “This is clearly not in the best interest of consumers,” he says.

A common scenario, he explains, is that a small study performed in a “limited” experimental environment — for example, in cell cultures or in animals — will link a certain plant chemical with a potential health benefit. The media reports on this finding, and then a supplement maker rushes to manufacture a supplement using the relevant chemical, which they’ll claim is “science-backed.”

“The current legal landscape permits this,” he says. “To regulate everything is not the answer, but the barrier of entry into the marketplace for supplements is very low.”

In his February press release, FDA’s Gottlieb detailed plans to beef up his agency’s research efforts and product-reporting requirements. The FDA has since announced plans to heighten public awareness of adulterated products. But experts say these changes, while welcome, won’t address many of their core concerns.

“There are really no laws that make supplement companies go through the FDA in the first place,” says Joanna Sax, a professor of law at California Western School of Law who has published papers on the supplement industry.

Sax explains that, unlike prescription drugs or over-the-counter medications, nutrition and health supplements are legally categorized as food products. This makes them exempt from many forms of oversight. “Drugs have to be tested for safety and efficacy before they go to market,” she says. “But in most cases, the FDA can remove a supplement from the market only if there’s a demonstrated harm, and they don’t know if there’s a harm until that harm has already happened.”

The FDA’s authority comes from Congress, she adds, and so their power to prevent risky supplements from getting into consumers’ hands is limited. (The FDA declined to comment for this story.)

There’s a counterargument to be made that, were the FDA granted the power to demand pharmaceutical-level testing of supplements, many people would be denied affordable access to products that could provide them real and meaningful benefits.

“Pharmaceuticals need to be vetted for efficacy and safety, and approved by the FDA through a process that can take 10-plus years and many, many millions of dollars,” says Amy Brown, an associate professor in complementary and integrative medicine at the University of Hawaii at Manoa who has researched herb and dietary supplements. “This process is not possible for dietary supplements that are not patented,” she says. The costs would chase away most manufacturers.

Still, other experts say change is needed. “I absolutely do think there should be increased regulatory oversight and supplement makers should have to show that their products are safe,” says Brigham and Women’s Manson. “Many come with risks and very few benefits.”

Regardless of how supplements are regulated, experts say it’s time people started thinking of these products as akin to prescription drugs.

“There’s a lot of distrust of the drug industry, and I think some consumers trust supplements more because they see them as ‘natural’ and not made by the drug companies,” Sax says. The irony is that the recent growth in the consumer supplement industry has largely been fueled by drug companies entering the fold.

“It used to be supplements versus Big Pharma, but now they’ve merged — supplements are Big Pharma,” UM’s Moyad says. “The drug companies saw how big complementary health was getting and they wanted a piece of the action.”

“There is a desire to go from point A to point B as quickly and easily as possible, and taking pills to do that is very chic right now.”

Based on his 33 years in medicine — much of which he’s spent studying supplements — Moyad says he approaches these products with the same caution he applies to drugs. “I understand and respect the power of pills,” he says. Like prescription drugs, supplements can help people with a diagnosed medical condition or deficiency. And like pharmaceuticals, supplements come with risks and side effects, he says.

He also practices what he preaches. “My colleagues can’t believe I don’t take anything,” he says. “And I tell them I don’t take anything, first of all, because I don’t need to take anything, and also because I’m not willing to be a guinea pig in a clinical trial of one.”

Asked for examples of times when supplements are clearly beneficial, he says there’s strong evidence that some products can benefit those at high risk for macular degeneration or skin cancer. There’s also good evidence that supplements can treat some disease-related symptoms.

There’s also no question that certain patient groups — as well as adults who, by choice or by necessity, are deficient in certain vitamins or nutrients — can make up shortfalls with supplements. “I’m primarily vegan, so I take a vitamin B12 supplement,” MD Anderson’s Cohen says. But he adds that, for healthy adults looking to mitigate their disease risks, supplements offer more downside than upside. “In the best case, they’re just a waste of money and you pee them out,” he says. “The worst case is over time there’s some kind of accumulation and toxicity.”

Over and over again, he and other experts say that eating a range of healthy whole foods is a better, safer, more-effective approach than taking supplements.

“Eat at least five servings a day of fruits and vegetables, eat whole grains rather than refined grains, avoid processed foods, eat at least two servings of fish a week,” Manson says. “If you’re vegetarian, try to get fatty acids from oils and nuts and seeds.”

Moyad agrees. “I have yet to come across any product that someone could sell me that was the secret to health or longevity,” he says. “But all the boring shit — a healthy diet, a good night’s sleep, exercise — the evidence for that has only become stronger.”

“There is a desire to go from point A to point B as quickly and easily as possible, and taking pills to do that is very chic right now,” he says. “I think we’ll get to a place where some supplements could have incredible value in disease treatment, but people need to wake up to the fact that if they’re experimenting on themselves with these products today, they could wake up in a few years and have done real harm.”

May, 2019|Oral Cancer News|

Tackling side effects in head and neck cancer treatment – the end of the road for hyperbaric oxygen?

Source: Cancer Research UK
Date: May 2, 2019
Author: Katie Roberts

Some side effects appear years after cancer treatment. That’s the case for one side effect of radiotherapy for head and neck cancer, called osteoradionecrosis.

This painful condition results from damage to the jaw bone, which often doesn’t heal properly and can cause bone fractures or even bone death.

It can develop without an obvious trigger, but it’s often linked to dental work like tooth extractions or implants. And it can happen even if the dental work is carried out 20 years after radiotherapy.

Professor Richard Shaw, a Cancer Research UK-funded head and neck surgeon at the University of Liverpool, treats the difficult condition quite frequently through reconstructive surgery.

Shaw says that these procedures are often bigger and harder than patients’ original cancer surgery, because they’ve already had so much treatment in that area.

For that reason, researchers have looked for ways to prevent osteoradionecrosis from developing. And that’s where hyperbaric oxygen comes in. It started with a small trial in the 80s, which has influenced the way doctors prepare patients for dental surgery ever since.

But new Stand Up To Cancer trial data, led by Shaw and published in the International Journal of Radiation Oncology, shows the hyperbaric oxygen hype may have been a bit premature.

The trial of hyperbaric oxygen

Back in the 1980s, a small trial in the US showed that giving hyperbaric oxygen before dental surgery could reduce the risk of osteoradionecrosis developing.

What is hyperbaric oxygen therapy?

Hyperbaric oxygen treatment involves sitting in a chamber where the oxygen is at a higher pressure than the air we normally breathe. It’s thought the increase in oxygen can help to promote healing. Sessions typically last 60-90 minutes.

“Prevention is obviously a very good idea, but I think there was concern around whether hyperbaric oxygen was the answer,” says Shaw.

A big question that lingered around the treatment was how applicable the 34-year-old trial results were to patient’s today. Radiotherapy has become a lot more targeted than it was a few decades ago, which may affect the risk of someone developing osteoradionecrosis.

“There really was no recent, good evidence for hyperbaric oxygen,” says Shaw.

No one wants to take the risk with our patients who, after all, had been cured of head and neck cancer and saw themselves as long-term survivors.

– Professor Richard Shaw

The verdict’s in

Shaw and his team ran a trial testing hyperbaric oxygen treatment in 144 patients who’d had head and neck cancer and now needed dental surgery. Half the patients had a course of hyperbaric oxygen before surgery, the other half didn’t.
Patients were then monitored after dental treatment to see who developed osteoradionecrosis, as well as monitoring pain levels and quality of life.

The first thing the team learnt was that osteoradionecrosis is a lot less common now than it was in the 80s.

“We can now say that with modern radiotherapy, someone’s risk of having this jaw problem is about 1 in 20. Which is a lot lower than the previous trial, which had shown it was around 1 in 3,” says Shaw.

The other big finding was that hyperbaric oxygen had no impact on the number of people developing osteoradionecrosis – the numbers were pretty much the same in each side of the trial.

And although people who had hyperbaric oxygen reported fewer short-term side effects and less pain immediately after surgery, there was no difference in long-term pain or quality of life between the two groups.

“It’s very clear that in our health system, hyperbaric oxygen is no longer justified,” says Shaw. “In some ways it could be reported as a negative finding, because hyperbaric oxygen didn’t work. But I think it has given us a definitive change of practice.”

What’s next?

As well as changing practice, the trial leaves another legacy: patient samples. Shaw is planning to use these to understand more about who develops osteoradionecrosis.

“What you’ll deduce with 6% of patients developing osteoradionecrosis in this trial is that 94% of people didn’t, even though they were considered high risk,” he says.

Right now, risk is assessed based on where the radiotherapy was aimed, as well as the type of follow-up dental work that’s being done. But Shaw believes risk could be predicted more precisely. The team will now study the patient samples to look if there are any differences in the DNA of patients who went on to develop osteoradionecrosis.

“We’re looking for a genetic signal or a ‘fingerprint’ that identifies people at high risk of osteoradionecrosis that we could validate in future trials,” says Shaw.

For now, Shaw says doctors can help to reduce the risk of osteoradionecrosis by making sure patients’ teeth are in the best possible condition before and after radiotherapy.

This, Shaw says, could help make sure “these conditions that require surgery don’t arise in the first place.”

May, 2019|Oral Cancer News|

Oral HPV DNA Persistence After Head and Neck Cancer Treatment Linked to Disease Progression

Source: genomeweb
Date: May 2, 2019
Author: Staff Reporter

NEW YORK (GenomeWeb) – Persistent traces of human papilloma virus DNA after treatment for HPV-positive head and neck cancer is linked to an increased recurrence risk, a new study has found.

Head and neck cancers affect some 53,000 people in the US each year, according to the National Cancer Institute, and HPV has been implicated in many of those cases. In general, patients with HPV-positive tumors have higher survival rates than those with HPV-negative tumors.

A team of MD Anderson Cancer Center-led researchers collected oral rinse samples from nearly 400 patients with head and neck squamous cell carcinomas at diagnosis and as their treatments progressed. As they reported today in JAMA Oncology, the researchers found that viral load in patients’ oral samples broadly decreased as they underwent therapy. But some patients’ viral loads persisted despite treatment, which was linked to an increased risk of cancer recurrence and death, the researchers reported.

“Our data suggest that a subset of patients with HPV-positive HNSCC at high risk for locoregional recurrence can be identified by detection of persistent, oral HPV after treatment,” MD Anderson’s Maura Gillison and her colleagues write in their paper.

The researchers enrolled 396 patients with oral cavity, oropharyngeal, or unknown primary HNSCC in their study. They tested the patients’ tumors for the presence of 13 high-risk HPV types using an mRNA expression test and found 202 patients had HPV-positive tumors.

At the same time, the researchers collected oral rinse samples from patients at diagnosis, after surgery, and at six months. Additionally, patients who underwent radiotherapy provided weekly oral rinse samples. The researchers tested these samples — a total of 2,922 oral rinse samples — for the presence of HPV using a multiplex PCR-based approach.

At diagnosis, patients with HPV-positive tumors were significantly more likely to have oral rinse samples positive for HPV than were patients with HPV-negative tumors. In particular, the researchers reported that the detection of any oral HPV DNA had a sensitivity of 84 percent, a specificity of 88 percent, a positive predictive value of 88 percent, and a negative predictive value of 84 percent for the diagnosis of an HPV-positive tumor.

The prevalence of oral HPV DNA, though, went down after treatment, the researchers reported. Prior to treatment, the prevalence of HPV DNA in oral rinses that matched that of HPV in the tumor sample was 69 percent. But after primary surgical resection, it was about 14 percent. Its prevalence fell similarly for patients who underwent radiotherapy, going from 85 percent before treatment to 9 percent after radiotherapy.

As expected, overall and recurrence-free survival was higher for patients with HPV-positive tumors than with HPV-negative tumors. Patients with HPV-positive tumors had a two-year overall survival of 91 percent, as compared to 75 percent for patients with HPV-negative tumors.

But for a subset of patients with HPV-positive tumors — about 14 percent — the prevalence of oral HPV DNA didn’t decline with treatment. These patients were more likely to recurrent disease, with about 45 percent experiencing disease recurrence within two years. Additionally, this subset had a lower two-year overall survival of 68 percent.

These patients, the researchers noted, might benefit from increased surveillance or adjuvant therapy.

The researchers added that their findings suggest that oral rinses to detect HPV DNA in head and neck cancer patients might be helpful. They cautioned, though, that its clinical utility might be limited by the need to identify tumor-type infections.

“Ongoing studies will evaluate whether multiplexed detection of plasma HPV DNA can improve these limitations,” the researchers added.

NOTE: This research was paid for in part by the Oral Cancer Foundation,www.oralcancer.org

May, 2019|Oral Cancer News|

Oral rinse could improve mouth pain associated with radiation therapy

Source: www.specialtypharmacytimes.com
Author: staff

An oral rinse containing diphenhydramine, lidocaine, and antacids, was found to significantly decrease pain caused by oral mucositis in patients undergoing radiation therapy for head and neck cancer compared with placebo, according to a study published in JAMA.

The multi-institution, randomized, double-blind, placebo-controlled phase 3 clinical trial was led by Robert Miller, MD, an emeritus Mayo Clinic radiation oncologist.

“Our group published a study in 2012 showing that an oral rinse of doxepin reduced oral mucositis-related pain compared to placebo,” Miller said in a press release. “However, there were no large randomized controlled trials studying the potential benefits of magic mouthwash.”

The researchers evaluated 275 patients between November 2014 and May 2016. The study revealed that treatment with both doxepin and the mouthwash combination significantly reduced pain associated with oral mucositis compared with placebo.

The doxepin and mouthwash combination treatment was also well-tolerated by patients, according to the study.

“Radiation therapy may cause mouth sores because it is designed to kill rapidly growing cells, such as cancer cells,” co-author, Terence Sio, MD, a Mayo Clinic radiation oncologist, said in a press release. “Unfortunately, healthy cells in your mouth also divide and grow rapidly, and may be damaged during radiation therapy, which can cause discomfort. We’re glad to have identified a proven method to help treat the discomfort of this side effect.”

Twitter lends insight to HPV-associated oral cancer knowledge

Source: www.oncnursingnews.com
Author: Brielle Benyon

The incidence of human papillomavirus (HPV)-associated oral cancer has risen in recent years, and the virus has now surpassed tobacco and alcohol use as the leading cause of the disease. In fact, while the HPV vaccine is typically associated with preventing cervical cancer, there have been more cases of HPV-associated oral cancer than there have been cervical cancer.1

While the link between oral cancer and HPV may be well-known to healthcare professionals, researchers at Howard University recently took to Twitter to get a glimpse into the public’s knowledge about the topic.

“By looking at the social media data, we wanted to know what people are hearing about oral cancer – especially HPV-caused oral cancer,” study co-author Jae Eun Chung, PhD, associate professor in the Department of Strategic, Legal & Management Communication at Howard University, said. “We wanted to see what the gaps are between the knowledge of the healthcare professionals and the public.”

The researchers collected 3,229 unique tweets over the course of 40 weeks using search terms such as “HPV or papilloma” and “mouth or oral or throat or pharyngeal or oropharyngeal.” They then used a program called nVivo 12.0 to conduct a content analysis that looked at certain phrasing, terms, and themes that commonly appeared.

More than half (54%; 1679 total) of the tweets had information about prevention, while 29% (910) were about the causes of oral cancer. Far fewer tweets were about treatment (5%; 141), diagnosis (3%; 97), symptoms (1%; 42), and prognosis (1%; 25).

Interestingly, the researcher discovered a prominence on the risk of HPV-associated oral cancer in men, with tweets that referred to males outnumbering tweets that referred to females in a 3:1 ratio. Also, the most popular hashtag used in the dataset was #jabsfortheboys, appearing in 89 tweets.

“There was a heavy emphasis on the risk of HPV-associated (oropharyngeal cancer) among men, which is different than what we see with HPV vaccination among girls,” Chung said. “That was very positive news to us, because HPV-associated (oral cancer) rates are higher among the male population and HPV vaccination rates are higher among girls.”

While spreading HPV vaccination and oral cancer is important on a global scale, the United States might have some catching up to do, as the 5 most mentioned Twitter users discussing the topic were located outside of the US–1 in New Zealand, 2 in Australia, and 2 in the United Kingdom.

“That’s kind of sad, because there are more Twitter users from the United States than from any other country,” Chung said.

Ultimately, Chung explained, these findings outlined an area where the country can benefit from more education and social media campaigns.

“In conclusion, this study provides some insight as to how the public makes sense of HPV-associated oral cancer,” she said. “More education and campaigns are needed, and US residents can benefit from more active involvement of US-based health education.”

Reference
1. Chung JE, Mustapha I, Gu X, Li J. Understanding public perception about human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) through Twitter. Presented at: D.C. Health Communication Conference; Fairfax, Virginia; April 26-27, 2019.

‘Whitish patch’: increase in oral dysplasia in young adults

Source: www.medscape.com
Author: Kristin Jenkins

Most 8-year-olds with a wiggly tooth expect the Tooth Fairy to tuck some money under their pillow. In the case of one little Canadian boy, his wiggly tooth got him an incisional biopsy, a diagnosis of oral squamous cell carcinoma (OSCC), a partial maxillectomy, and a defect that was closed with local advancement flaps.

“This was the most unusual case we’ve seen,” said Marco A. Magalhaes, DDS, PhD, assistant professor of oral pathology and oral medicine in the Faculty of Dentistry at the University of Toronto in Ontario, Canada.

“OSCC predominantly affects patients 40 years of age and older,” write Magalhaes and colleagues in a case study report published in November 2016 in Oral Surgery Oral Medicine Oral Pathology Oral Radiology. “It is extremely rare in patients younger than 20 years of age.”

The clinical, radiographic, and histologic findings in this young patient were distinctive. Although the diagnosis and treatment were challenging, the clinical course was favorable at follow-up, the authors said. This case illustrates the fact that even pediatric patients can be at risk for OSCC. Magalhaes said that he and other dentists are concerned about the rising number of OSCC cases in patients who are in their 20s and 30s. These patients have no known risk factors and are often without symptoms. Many are diagnosed with high-grade oral epithelial dysplasia (OED) that rapidly progresses to cancer, Magalhaes told Medscape Medical News.

“When you look at the distribution of cases of oral dysplasia or carcinoma, you see that they tend to occur in older males in their 50s with a history of smoking and a low risk of [malignant] transformation,” he explained.

“What we are seeing in practice, however, is a lot of dysplasia in younger individuals without risk factors. These cases are the most concerning,” he commented.

At the time of presentation, patients may say, “I’m not sure why I’m here, but I saw a whitish patch in my mouth,’ ” said Magalhaes.

Others may be asymptomatic and have “absolutely no concerns,” he pointed out. “Unfortunately, this story is becoming more common.”

Nonhealing Sore in Mouth
Oral cancer usually presents as a nonhealing sore that is often painful. OED can be more difficult to diagnose because it manifests as a faint whitish or red patch anywhere in the oral cavity.

The gums, tongue, soft palate, and the inside of the cheeks can be affected. Most commonly, the floor of the mouth is affected.

Currently, Magalhaes and colleagues are conducting a review of more than 3000 cases of dysplasia in Ontario to determine group distribution, pattern, and, potentially, risk factors.

Although oral cancer has multiple causal factors, Magalhaes noted that smoking is “by far” the most significant and well-recognized risk factor. Heavy alcohol consumption is also a well-known risk factor. Human papillomavirus accounts for 5% to 6% of oral cancers, he noted.

A regular dental checkup is important, and early detection is critical for survival, Magalhaes emphasized.

For high-grade OED, the risk for progression to frank carcinoma is 18% to 30%, he noted. For moderate-grade OED, the risk is 10% to 15%, and for low-grade oral dysplasia, it is 1% to 4%.

“Physicians should reinforce to their patients the importance of dental checkups at least twice a year,” Magalhaes said. “This alone would increase the chances of early lesion detection.”

Review of Biopsy Specimens
A recent review of 63,483 biopsy specimens submitted by dentists to the Toronto Oral Pathology Service (TOPS) primarily from 2005 through 2015 bears this out. The review, led by Magalhaes, was published online April 25 in the Journal of the American Dental Association.

TOPS is operated by the Faculty of Dentistry at the University of Toronto and is one of the largest oral pathology services in Canada, noted Magalhaes, who works there.

The results show that generally, the incidence of OED (2679 cases) and OSCC (828 cases) in Ontario remained stable from 2005 to 2015. It also showed that when it comes to early detection of oral lesions, dentists have seriously stepped up their game. During the 10-year period, detection of OED by dentists increased 3.8-fold. The number of OSCC cases they detected doubled. OSCC accounted for about 10% of all oral cancers in the province in 2015.

“These biopsy specimens were submitted mostly by specialists in oral and maxillofacial surgery, periodontics, endodontics, and oral and maxillofacial pathology and oral medicine,” the authors write.

“However,” they continue, “informal discussion with clinicians who submitted the biopsy specimens has indicated that the initial detection of the mucosal abnormality was often accomplished by the general practice dentist, dental hygienist, or both, who referred the patient to specialists for evaluation, biopsy, and case management.”

The study also shows that potentially malignant lesions made up 4.68% of all cases and that OED accounted for 90%. An increased awareness of early lesions with malignant potential can result in early diagnosis and decreased morbidity and mortality from OSCC, the researchers say.

Both dentists and patients appear to be maintaining a high index of suspicion, according to Magalhaes.

“Dentists are increasingly aware of the presence of these early lesions and are either biopsying them themselves or sending them for biopsy,” he explained. “We’ve also noticed that patients are more aware of mouth changes and are asking dentists about lesions that they have identified.”

During a routine dental checkup, an examination for early signs of oral cancer is performed. This includes inspection of the lymph glands in the neck and a check of all mucosal surfaces in the oral cavity for signs of ulcers or red or white patches.

The severity of OED determines treatment, noted Magalhaes. In cases of low-grade OED, the lesion is monitored every 6 months, and a repeat biopsy is performed if warranted. A high-grade OED that is accessible and relatively well contained is treated with complete surgical excision. This is followed by monitoring two or three times a year. When the lesion is diffuse, affects 60% of the oral cavity, or extends into areas that are difficult to access without significant morbidity, the patient is closely monitored with examinations four times a year, he said.

Source:
J Am Dent Assoc. Published online April 25, 2019. Abstract

Oral Surg Oral Med Oral Pathol Oral Radiol. 2016 Nov;122:e179-e185. Full text