Monthly Archives: January 2015

Researchers discover genetic fingerprint of HPV virus in some head and neck cancers

Author: Staff

A large US study(link is external) has pinpointed genetic errors that mark out head and neck cancers caused by the human papillomavirus (HPV).

If confirmed in further studies this could be used to develop potential new treatments.

Head and neck cancers include tumours of the throat, mouth, nasal cavity, larynx, salivary gland among other tissues and organs.

Some are linked to tobacco or alcohol use, while others are caused by infection with HPV, more commonly associated with cervical cancers.

Rates of HPV-linked head and neck cancers are on the increase.

The US study, published in the journal Nature, was carried out as part of The Cancer Genome Atla (TCGA) project.

Using cutting-edge DNA analysis, the team found several similarities between the DNA from head and neck tumour cells and other cancer types – as well as new subtypes of smoking-related head and neck cancer.

The US team studied samples from 279 head and neck squamous cell carcinomas (HNSCC) from untreated patients, around eight in 10 of whom were smokers. Most of the samples were oral cavity cancers and larynx cancers (61 per cent and 26 per cent respectively).

The researchers found that specific alterations in genes called FGFR3 and PIK3CA – which produce important protein molecules that help cells grow – were common in many patients with HPV-related cancers.

These genes are also present in a wider set of faults found in smoking-related tumours.

But faults in the epidermal growth factor receptor (EGFR) gene, which produces another important growth molecule, were rare among HPV-positive cancers, despite being frequently altered in HPV-negative tumours.

Similarities between the DNA of head and neck tumours cells and other cancers – including squamous cell lung cancer, and cervical cancer – were also found, suggesting there may be common paths of cancer development – and potentially treatment.

Calling the study “important”, Professor Nick Coleman – a Cancer Research UK expert in HPV and cancer – went on to say: “It greatly improves our understanding of the biology of head and neck cancer, pinpointing crucial genetic differences between those tumours caused by HPV infection, and others linked with risk factors like smoking.

“HPV-linked head and neck cancers are becoming more common, and this study suggests that the virus may trigger a small number of genetic faults that are causing the disease. This opens up important new avenues of research, with the possibility of developing treatments targeted to these faults to help tackle head and neck cancer in the future.”

Director of the National Human Genome Research Institute in the US, Dr Eric Green, said that the new findings “help establish a genomic map of various head and neck cancers, provide new insights into other similar cancers and may further our understanding of how viruses can impact disease.”

For more information:

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
January, 2015|Oral Cancer News|

How Anti-Vaxxers Ruined Disneyland for Themselves (and everyone else)

Author: Robbie Gonzalaz

“The Happiest Place On Earth” is ground zero for a recent measles outbreak centered in California. Now, unvaccinated people are being warned to avoid visiting Disneyland parks.

No Infants In Disneyland

There are now 67 confirmed cases of measles in an ongoing outbreak centered in California. According to the California Department of Public Health, 59 of the cases are in-state. Among the 34 California patients for whom vaccination status is known, 28 were unvaccinated and one had received partial vaccination. Only five were fully vaccinated.

Forty-two of the California cases have been linked to an initial exposure at Disneyland or Disney California Adventure Park, and while cases were originally tied to people who visited the park in mid-December, state health officials now note other cases visited Disney parks in January. According to the CDC, the majority of measles cases reported so far during 2015 have been part of the “large, ongoing outbreak” connected with these parks.

Last year, there were 644 measles cases documented in 27 states – the biggest annual numberin close to a quarter century. For those hoping to avoid seeing similar infection rates in 2015, the year is off to an inauspicious start.

Unvaccinated people are now being warned to avoid visiting Disneyland parks. The reasoning is simple: Most people who get measles are unvaccinated, and the disease spreads easiest when when it reaches a community where large groups of people are unvaccinated. Limiting the number of unvaccinated people in the park therefore not only protects them from themselves, it protects the immunized visitors, as well.

It also protects those too young to be immunized. Of the measles patients who have been hospitalized in this recent outbreak, six cases have been in infants too young to be vaccinated, whether their parents want them immunized or not.

“I would recommend that infants are not taken to places like Disneyland today,” said Gil Chavez, deputy director of the California Department of Public Health’s Center for Infectious Diseases, in an interview with the LA Times. Yesterday, Chavez implored parents to take action to protect not only their own children, but other children who might be affected by their decisions.

“I am asking unvaccinated Californians to consider getting immunized,” Chavez said. “We have a particular responsibility to protect all of our infants in the state until they are old enough to be vaccinated.”

This is how the anti-vaccination movement ruined Disneyland, not just for those who would actively refuse vaccines, but for everyone else. The cause for measles’s resurgence is as unambiguous today as it has been in recent months. Last May, Dr. Anne Schuchat, assistant surgeon general and director of the CDC’s National Center for Immunization and Respiratory Diseases stated unambiguously that “the current increase in measles cases is being driven by unvaccinated people.” Yesterday, pediatric infectious disease specialist James Cherry told the New York Times that the Disneyland outbreak was “100 percent connected” to the anti-vaccine movement. “It wouldn’t have happened otherwise — it wouldn’t have gone anywhere,” he said.

When Anti-Vaxxers Cluster

Of course, the ill-effects of the anti-vaccination movement are not limited to Disneyland. The consequences of refused vaccinations are felt anywhere that people gather, allowing diseases like measles to spread vast distances very quickly. Venues like theme parks and airports are considered potential flashpoints, because they see a lot of international travelers, who may originate from countries where diseases like measles have yet to be eliminated.

Schools also pose a serious challenge. While state officials have not gone so far as to ban unvaccinated people from visiting Disneyland altogether, such measures have recently been taken at California schools. Health officials in Orange County this week issued more than 20 letters to parents stating that students who could not prove they had received a measles vaccine could be barred from class. (The Journal of the American Medical Association has published research this week on legal strategies for combating the growing danger of nonmedical vaccine refusal.)

The major concern of California health officials is that school vaccination rates remain above 95% – a threshold critical to maintaining herd immunity. Statewide, the vaccination exemption rate among California kindergartners was 3.1% for the 2013–2014 school year, but there are pockets across the state where exemption rates have crept into the double digits.

A newly published study on anti-vaccination patterns is the latest to highlight some of these pockets. The study, which was led by Kaiser Permanente Division of Research Director Tracy Lieu and appears in this week’s issue of the journal Pediatrics, finds that parents who opt out of vaccinating their children tend to cluster, creating geographic hot-spots where large percentages of children receive no vaccines or are under-immunized. The findings could explain how a disease like measles – which was officially “eliminated” from the U.S. in 2000 – has managed to acquire so firm a foothold within the American population.

NPR’s Liza Gross reports on the study, and an ironic consequence of this clustering effect:

“If these parents were distributed randomly, their decisions would be less likely to harm others, especially babies too young for vaccination. But parents who use personal belief exemptions to avoid school vaccination requirements often live in the same communities, studies have found.

And parents of children too young to go to school do, too… These younger children face the highest risk of dying from whooping cough and other vaccine-preventable diseases.

…The main problem with this clustering behavior, says [Saad Omer, a researcher at Emory University who found that clusters of personal belief exemptions contributed to the 2010 California whooping cough epidemic that killed 10 babies], is that every child’s risk for disease depends on what others do. That’s because no vaccine is 100 percent effective, so even a vaccinated child could get sick if exposed.”

Lieu’s team also identified five clusters where all vaccines were refused for close to 9,000 babies and toddlers in the study:

– 10.2 percent of children in an area from El Cerrito to Alameda

– 7.4 percent in northeastern San Francisco

– 6.6 percent in Marin and southwest Sonoma counties

– 5.5 percent in northeastern Sacramento County and Roseville

– 13.5 percent of kids in a small area south of Sacramento

“These are early signals,” says Lieu. “These kinds of clusters can be associated with later epidemics.”

In an interview with the NYT, Jane Seward, deputy director of the viral diseases division at the CDC, echoes Lieu’s sentiment:

“The problem is that there are these pockets with low vaccination rates… if a case comes into a population where a lot of people are unvaccinated, that’s where you get the outbreak and where you get the spread.”


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


January, 2015|Oral Cancer News|

Inherited factors linked to head and neck cancers in young adults

Author: Oxford University Press

An article published online today in the International Journal of Epidemiology pools data from 25 case-control studies and conducts separate analyses to show that head and neck cancers (HNC) in young adults are more likely to be as a result of inherited factors, rather than lifestyle factors such as smoking or drinking alcohol.

Approximately 550,000 new cases of HNC are diagnosed worldwide annually, with an increased incidence in young adults (YA) also being reported. In particular, reports indicate an increase in tumours affecting the tongue and oropharynx among young adults in Europe, the United States, India, and China.

Dr Tatiana Natasha Toporcov and colleagues pooled data from 25 studies from the International Head and Neck Cancer Epidemiology (INHANCE) consortium to compare the role of major risk factors and family history in HNC for YA (45 years of age or younger) and older adults (over 45 years of age). Participants were surveyed about their history of cigarette smoking, alcohol drinking, and diet, as well as family history of cancer. In total, there were 2,010 cases and 4,042 controls in YA, and 17,700 cases and 22,704 controls in older adults.

The attributable fraction (an estimate of the proportion of cases which could be avoided if the exposures were eliminated) for smoking on the risk of HNC was 20% in young women, 49% in older women, 46% in young men, and 64% in older men. The attributable fraction for drinking alcohol on the risk of HNC was 5% in young women, 20% in older women, 22% in young men, and 50% in older men. Eating a diet rich in fruits and vegetables was shown to be inversely associated with the risk of HNC in both age groups.

Dr Toporcov says: “To our knowledge, this is the largest study to evaluate the role of the major risk factors for HNC in young adults as well as to compare risks in younger and older patients. The large sample size allowed us to elucidate any differences in the role of risk factors in HNC in YA according to age group, sex and cancer sub sites.

“Although they were less likely to be drinkers and/or smokers, alcohol consumption was a risk factor for HNC in YA. However, a stronger association with heavy drinking was observed for the older group. Our results also indicate that the inverse association with fruit and vegetable intake is similar among young and older populations. YA were more likely to have been diagnosed with oral and oropharynx cancer than older adults. Also, early onset cancer in the family was associated with HNC risk only among YA.

“Our results support public health efforts to decrease exposure to major risk factors for HNC in the population regardless of age. However, investigations of the role of other risk factors, such as human papilloma virus and inherited characteristics, on HNC in the younger age group are warranted.”

January, 2015|Oral Cancer News|

Keratinization may be prognostic in certain head and neck cancers

Author: T. Cooper

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

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

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

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

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

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

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

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

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

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

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

January, 2015|Oral Cancer News|

Why the “Cancer Due to Bad Luck” Story Needs Revising

Author: Zosia Chustecka

UPDATED January 16, 2015 // There has been quite a backlash to the recent news that many cancers are due to “bad luck” of random mutations, which was proclaimed in headlines around the world, and based on a report published in the January 2 issue of Science.

The International Agency for Research on Cancer (IARC), the World Health Organization’s specialized cancer agency, put out a press release to say that it “strongly disagrees with the conclusion,” and warning that the message could harm cancer research and public health.

“We already knew that for an individual to develop a certain cancer there is an element of chance, yet this has little to say about the level of cancer risk in a population,” explained IARC director Christopher Wild, PhD. “Concluding that ‘bad luck’ is the major cause of cancer would be misleading and may detract from efforts to identify the causes of the disease and effectively prevent it.”

As previously reported by Medscape Medical News, the researchers, from Johns Hopkins University in Baltimore, reported that in about two-thirds (22 of the 31) of cancer tissue types they had investigated, the cancer could be largely explained by the bad luck of random mutations that arise during DNA replication in normal noncancerous stem cells.

However, many of the news stories reported a distorting simplification of the findings, and stated that two-thirds of all cancers are due to bad luck.

There has been fierce criticism of the way that the media reported the story, but an expert argues that journalists were misled.

The Science report was accomapnied by an editorial entitled “The Bad Luck of Cancer,” and the subheading added: “Analysis suggests most cases can’t be prevented.”

But the data do not support either of these ideas, noted George Davey-Smith, MD, a clinical epidemiologist at Bristol University, United Kingdom, in a BBC News report. He also noted that “in the press release [from the Johns Hopkins School of Medicine], the authors say they’ve come up with a method to quantify the contribution of these stochastic or chance factors, which their method doesn’t,” he adds.

“It’s both in the journal and in the press release so it’s just not fair to attribute the mis-reporting of this to journalists,” Dr Davey-Smith commented.

In reaction to the huge media uptake of the story, the study authors issued further comments in a Johns Hopkins University statement, which also included the press release that had been “ammended for clarity.” The public relations officer for Johns Hopkins University, Vanessa Wasta, MBA, noted that the press release was updated to change reference from “incidence” to “risk” as a clarification in the first paragraph, but pointed out to Medscape Medical News that the original news release contained no reference to “cases” or “all” cancers, but referred to “risk” many times.

Dr Tomasetti also said that many scientists and statisticians had also needed clarification, and that the team is now working on a technical report with additional details.

In the end, the amount of media attention given to this study was not justified by the findings, Dr Davey-Smith said in the BBC News report. “Explaining the difference in risk between the leg and the lung is of no interest to anyone and says nothing about the contribution to cancers in the population,” he commented.

The research does contain an important message for people who have cancer and lead a healthy lifestyle, according to another commentator. P.Z. Myers, PhD, a biologist and associate professor at the University of Minnesota, Morris, told the BBC: “What’s important about the study is that it does say that if you have cancer — and I think this is something people who have cancer would like to hear — it’s not something you should blame yourself for.”

Half of All Cancers Can Be Prevented, Says IACR

The IACR took issue with the study conclusion “that random mutations (or ‘bad luck’) are the major contributors to cancer overall, often more important than either hereditary or external environmental factors.”

The authors of the report, Dr Tomasetti and Bert Vogelstein, MD, Clayton Professor of Oncology at Johns Hopkins and codirector of the Ludwig Center, argue that for many cancers, there should be a greater focus on the early detection of the disease rather than on prevention of its occurrence. But the IACR warns that “if misinterpreted, this position could have serious negative consequences from both cancer research and public health perspectives.”

The agency points out that, although it has long been clear that the number of cell divisions increases the risk for mutation and, therefore, for cancer, a majority of the most common cancers occurring worldwide are strongly related to environmental and lifestyle exposures, and therefore they are, in principle, preventable.

“Based on current knowledge, nearly half of all cancer cases worldwide can be prevented,” the agency states. “This is supported in practice by rigorous scientific evidence showing decreases in cancer incidence after preventive interventions. Notable examples include drops in rates of lung cancer and other tobacco-related cancers after reductions in smoking, and declines in hepatocellular carcinoma rates among people vaccinated against hepatitis B virus.”

In addition, the agency points out that the past 5 decades of international epidemiological research have shown that most cancers that are frequent in one population are relatively rare in another and that these patterns vary over time. For example, esophageal cancer is common among men in East Africa but rare in West Africa. Colorectal cancer, once rare in Japan, has increased 4-fold in incidence in just 2 decades.

“These observations are characteristic of many common cancers and are consistent with a major contribution of environmental and lifestyle exposures, as opposed to genetic variation or chance,” the agency comments.

Criticisms of the Study

The agency also points out several limitations of the study itself. These include the emphasis on very rare cancers (e.g., osteosarcoma, medulloblastoma) that together make only a small contribution to the total cancer burden. The report also excludes, because of the lack of data, common cancers for which incidence differs substantially between populations and over time. The latter category includes some of the most frequent cancers worldwide (for example, those of the stomach, cervix, and breast, each known to be associated with infections or lifestyle and environmental factors). Moreover, the study focuses exclusively on the United States population as a measure of lifetime risk. The comparison of different populations would have yielded different results, the agency contends.

Other researchers have also raised questions over the way in which the research was conducted, and the research has stimulated much detailed discussion, including several blog posts from scientists, and a lengthy blog post from US oncologist David Gorski, MD, on the Science-based Medicine website. He comments that the message from the study is unpopular, adding that “human beings don’t want to hear that cancer is an unfortunately unavoidable consequence of being made of cells that replicate their DNA imperfectly over the course of our entire lives. There’s an inherent hostility to any results that conclude anything other than that we can prevent most, if not all, cancers if only we understood enough about cancer and tried hard enough.”

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
January, 2015|Oral Cancer News|

Patients undergoing radiation therapy benefit from animal assisted therapy

Author: staff

According to a recent study published in the Journal of Community and Supportive Oncology, therapy dogs can help improve the emotional state of some cancer patients undergoing radiation therapy.

The study, developed by Mount Sinai Beth Israel researchers, found that cancer patients who are undergoing intensive multi-modal concomitant radiation therapy together with chemotherapy for gastrointestinal, head and neck cancers, benefited from therapy dog’s visits in terms of their emotional well-being and life quality, even during therapy phases where physical decline was more pronounced.

This research was funded by The Good Dog Foundation, a provider of professionally trained therapy dogs, Zoetis, an animal health company and the Pfizer Foundation.


“This study is the first such definitive study in cancer, and it highlights the merits of animal- assisted visits using the same scientific standards as we hold for the cancer treatment itself. It shows the importance of an innovative environmental intervention during cancer treatment,” Stewart B. Fleishman, MD, principal investigator and Founding Director of Cancer Supportive Services at Mount Sinai Beth Israel, said in a news release. “Having an animal-assisted visit significantly improved their quality of life and ‘humanized’ a high-tech treatment,” he said. “Patients said they would have stopped their treatments before completion, except for the presence of the certified Good Dog Foundation therapy dog and volunteer handler.”

“Thanks to this rigorously designed study, we now have strong evidence that pet therapy is an effective tool to help cancer patients get through challenging treatments,” added Gabriel A. Sara, MD, Medical Director, Infusion Suite at Mount Sinai Roosevelt, and Assistant Clinical Professor of Medicine, Icahn School of Medicine at Mount Sinai.

Researchers evaluated the outcome of certified therapy animal-assisted visits on patient’s life quality as they were undergoing multi-modal treatment for head and neck and gastrointestinal cancers. A total of 37 patients completed the study, receiving 15 to 20 minutes of animal-assisted visits every day throughout 6 weeks.

Most patients received 30 radiation therapy treatments in addition to their chemotherapy sessions, and presented signals of fatigue, fear, weight loss, and many patients had feeding tubes.

The results showed that patients significantly increased their social and emotional well-being.

“There is mounting evidence in human and veterinary medicine that the emotional bond between people and companion animals can have a positive impact of emotional and physical health,” J. Michael McFarland, DVM, DABVP, Zoetis group director of Companion Animal Veterinary Operations, said in the news release. “These new results help advance our understanding of the value of animal-assisted therapy in cancer treatment and point to the ways the oncology and animal health communities can work together in supporting cancer patients achieve the best possible treatment outcomes.”

Rachel McPherson, Executive Director and Founder of The Good Dog Foundation added, “We are excited to see the results of this peer-reviewed study, which bears out scientifically what we have seen for more than sixteen years at The Good Dog Foundation, which is that highly trained and fully certified therapy dogs can provide critical healing services to help change cancer patients’ experiences for the better as they receive treatment.”

January, 2015|Oral Cancer News|

Kramer: Our cancer risk is not written in the stars

Author: Matthew Ong, reporter with The Cancer Letter

The stochastic process of stem cell divisions should not be equated with bad luck, said Barnett Kramer, director of the NCI Division of Cancer Prevention, focusing on misinterpretations of the “Bad Luck” paper by Cristian Tomasetti and Bert Vogelstein, of Johns Hopkins University School of Medicine.

Kramer spoke with Matthew Ong, a reporter with The Cancer Letter.

Matthew Ong: What was your overall impression of the Tomasetti and Vogelstein paper?

Barnett Kramer: I found the paper interesting. What they did was they didn’t generate any new experimental evidence, obviously. They searched the literature for reports on numbers of stem cells and number of divisions of the stem cells.

They used well-accepted concepts that the risk of mutations or number of mutations are relatively constant for a given cell division—in statistical terms, a stochastic process—that is, any given division, you don’t know which gene is going to mutate, but for every given division, you can predict, relatively accurately, how many mutations are going to occur in the division.

You just don’t know which cell it’s going to happen to. But if you have enough cells, then a statistical analysis of this stochastic process gives you, generally, a pretty good idea of how many mutations there are, and the number of mutations to be a risk factor for cancer.

MO: What were the authors trying to achieve in their analysis?

MK: They took well-known concepts, went to the literature, looked for the number of stem cells in any given class of tumors or tissue type, and looked for reports of the number of divisions.

The innovation they added—actually directly plotting the number of anticipated mutations or divisions with the cancer risk—and what I found interesting was that, relative to most biological processes, they got a pretty tight correlation between the number of stem cell divisions and the risk of cancer.

The variation in cancer risk across the tumor types for which they had any data was about 65 percent, and that pretty tight correlation, in biological terms. So it fits with the existing notions of the association between mutations and cancer. I found that interesting. I think they took existing literature and results and, for the first time to my knowledge, plotted them looking for variation across cancers using that information and got a tight correlation.

So it’s not conceptually different from what was, in essence, accepted, in terms of the association, but what they did was plot it graphically, and as it often happens, you get some biological input by taking existing data and graphing them.

That’s what I took as particularly interesting in the paper. I wouldn’t have predicted that the correlation would be quite that high, and so I found it intriguing that it was. That’s the good part.

MO: What have news reports missed in their coverage of the paper’s findings?

BK: On the parts that I think may have either been misinterpreted or picked up in the press and took an extra step too far, was going beyond the actual data to some of the implications. I don’t think that, given those observations, you can conclude with any confidence what would be the best strategy to decrease mortality for a given cancer.

I don’t think that tells you a priori whether the best strategy will be screening; or the best strategy will be primary prevention; or the best strategy will be treatment. Unfortunately, you’re left with the hard grunt work of testing various strategies to see which is the most effective amongst the three for decreasing mortality.

A case in point would be that they unfortunately didn’t have reported evidence on stem cells or stem cell divisions from two very common cancers—prostate cancer and breast cancer—and for both of those cancers we at least have some evidence about whether or not screening works, or how effective it is, and it would have added to the paper if they had some stem cell division data on those. There have been randomized trials at least to test the inference that screening would or wouldn’t work.

The next important thing, which I think was sort of missed in the press—even the paper itself says something that appears to equate that stochastic process with bad luck. I personally think that the use of the phrase “bad luck” can be easily misinterpreted. Stochastic processes have a crisp scientific definition, but bad luck doesn’t. The lay public may interpret incorrectly in this case, in my opinion, that bad luck simply means “it’s in the stars, it’s your fate, there’s nothing you can do about it.” And bad luck is not equivalent to random mutations in a stochastic process.

MO: What would be a good analogy?

BK: Let’s say you’re dealing with traffic patterns. The heavier the traffic, the more accidents there are going to be. There is a tight correlation between the number of cars on the roads and the number of accidents, but that doesn’t mean that it’s pure bad luck if you have an accident.

Statisticians can predict that, for a given road at a given time and given road conditions, that there’s going to be a certain risk and a certain number of accidents. And the correlation almost certainly is going to be very tight, but that doesn’t mean that the individual car driver has no control, and might as well give up because whether they have an accident is purely bad luck. They can choose to drive differently.

So aggressive drivers are at a higher risk than slower or safer drivers. And the same is true for speed limits. It’s well known and it has been well described that for every mile per hour that you raise the speed limit, or every five or 10 miles per hour, the rate of mortalities or fatalities can go up.

But that doesn’t mean for an individual driver, it’s just pure bad luck. Because individual drivers and individual cars have a different risk of traffic fatality depending on how they drive, even if they’re driving at the same speed in the same speed zone.

The other thing which was not picked up by most of the press was that the correlation they were even looking at, leaving aside the issue of cause and effect, because this isn’t even designed to determine cause and effect—they were looking at classes of tumors.

They lined up 31 classes of tumors, and they found out that the correlation was surprisingly high, and I found that interesting. But they were not looking at risk of individual tumors. Even if it were true that two-thirds of the variability among tumor types is associated with the number of stem cell divisions, it doesn’t mean that two-thirds of all cancers are predetermined.

Let’s say you have an extremely common tumor and ten extremely rare tumors, and you plot the number of stem cell divisions for those 11 tumors. The 11 tumors may line up very nicely along that diagonal line, that is, they fit a pattern that, across tumor types, there is a pretty tight association between stem cell divisions and cancer risk.

But remember, the most common tumor accounts for most of the cancers. And if that most common tumor is attributable in large measure to a known environmental carcinogen, then the overwhelming majority of cancers, individual cancers, will be preventable. And so a clear case in point would be lung cancer, which we know that 90 percent of lung cancers are probably attributable to smoking and preventable if people don’t smoke at all.

And yet there are many, many rare tumors for which we don’t have any known environmental cause, and even in the aggregate, if you add them all up, they don’t come anywhere close to the number of lung cancers.

So just one simple preventive intervention would prevent the overwhelming majority of all those cancers even if the association tells you that, across cancer types, two-thirds are due to stochastic process of mutation.

Let’s say there were only five cases of every other cancer type there is, and they added up to a total of 200 cases a year, and there were 150,000 cases a year of lung cancer, 90 percent of which were attributable to smoking, then the overwhelming majority of individual cancers would be preventable, even if a regression curve tells you that across cancer classes, there is a pretty tight correlation with stochastic processes.

And in this case, let’s take lung cancer, which we know 90 percent are preventable by no smoking, and skin cancer, especially non-melanoma skin cancer—which is more common than all the other cancers combined, including lung cancer—and we know that non-melanoma skin cancers are largely preventable by avoiding intensive sun overexposure, the biggest risk factor for non-melanoma skin cancer.

The number of non-melanoma skin cancers just completely outweighs all other cancers combined. And so, even though skin cancer fits on that regression line, and is part of the pattern of cancer types, sun avoidance would still prevent an inordinately large number of total cancers in the country.

Unfortunately, the term “bad luck” got picked in a number of news outlets. Just the term bad luck can be misleading. Bad luck just means, to most people, “nothing you can do about it, you are meant to have cancer.” And since the term was—for the sake of simplicity or I would say, over-simplicity—equated with a more precise statistical phenomenon, stochastic risk.

That led to the sense that, “Gee, there’s not much you can do about cancer, it’s just all in the stars.” That has an unfortunate connotation, and I think that was the biggest error of translation of the results.

Lawmakers, and physicians, by the way, and health professionals and the lay public often respond to news articles, and if they are misinterpreted, then it can lead to policy decisions, which are obviously made on behalf of the lay public.

 (click to enlarge)


MO: Do you have any other observations that you’d like to highlight?

BK: Another thing I wanted to point out that I found interesting in Figure 1 of the paper—the correlation seems good relative to many biological phenomenon. One thing I took from it, and it wasn’t emphasized in the article, is that you can sort of visually look at the vertical distance between any given individual cancers on that regression line.

The further it is away from the regression line, the more that one could suspect that there is something going on, if it is cause and effect, there’s something additional going on that explains the higher incidences for the curves that are well above the line. And sure enough, that fits the pattern very nicely, so it’s interesting to look at.

The best example is lung cancer. When you look at lung cancer (smokers) and lung cancer (nonsmokers), there is a very large vertical difference between those. So lung cancer (smokers) and you’d expect, the point is way above that regression line.

And the same is true, for example, for HPV head and neck cancer and other cancers, and hepatitis B liver cancer is way above the line relative to the rest of liver cancer. It fits that one would say, “Gee, the further vertically the point is from the line, especially if it’s north of the line, the more may be going on, over and above the stochastic random process.”

That is one indicator that something else might be going on, is how far above, vertically, the regression line, a given point is. That’s not pure, it’s very rough, but nevertheless, if you look at some of the points, they fit that pattern.

General colorectal cancer is right on the regression line, but those with a genetic predisposition (FAP) for colorectal cancer are way above that regression line vertically. Each of those points that are very far away from the line seems to fit that pattern.

Now, always, an environmental carcinogen, you have to be very cautious before you say, it must be an environmental carcinogen. A case in point is thyroid follicular cancer—the incidence may be driven by screening for thyroid cancer and screening tests are much better at picking up thyroid follicular than other forms of thyroid cancer. So all it means is that the incidence is considerably higher than you have expected simply based on the formula of stem cells and number of divisions.

I think that we can be pretty confident that there are some causative reasons for the vertical difference. Certainly, we can be confident in the case of smoking and lung cancer. That’s a well-established causative factor. I think we can be confident in the case of HPV infections for head and neck cancer. We’re pretty confident that that’s causative.

In the case of thyroid follicular cancer, I think the weight of evidence is that screening increases the risk of thyroid cancer even if there are no known new carcinogens. And I think there is a large body of evidence that some of the incidence, and sometimes a large measure of incidence in some cancers, is attributable to screening and overdiagnosis, such as picking up very indolent, non-life threatening cancers just by simply dipping into a reservoir of silent, non-progressive tumors with a screening test.

January, 2015|Oral Cancer News|

Five game changers: will they alter the course of dental hygiene treatment?

Author: Karen Davis, RDH, BSDH

With the beginning of a new year, clinicians may be wondering what new technologies or services they should consider. As I reflected on this, it led me to consider what has the potential to become game changers for dental hygienists. I immediately considered the integration of laser technology, sharpen-free instruments, ergonomic operator chairs, CAMBRA, adjunctive devices for caries detection, and oral cancer screenings. Within minutes, I had a list of about 25 technologies and services that have completely altered how I practice dental hygiene from the day I started in 1979. So I decided to feature a few technologies I believe are underutilized or, in a few cases, even unknown by clinicians who have the potential to substantially alter patient care.

Automated and unassisted periodontal charting
In the world of dental hygiene, having another person enter data into the computer or record periodontal data is either a luxury or is uncommon. Dental hygienists everywhere seem caught in the time trap of laboriously entering the data or, in many cases, settling for spot probing and incomplete data collection. But automated technologies to collect and enter the data unassisted have been available to dental hygienists for decades, and when integrated, have the potential to help diagnose periodontal diseases in the earliest possible stages.

Dental R.A.T. (Remote Assisted Technology) is a foot-operated device that enables the clinician to enter periodontal data unassisted using hand-eye-foot coordination. It integrates to major software programs, automatically entering the data into periodontal charts, and also enables access to radiographs and other data, such as an intraoral camera in the patient’s record, with the touch of a foot pedal. Once numbers are entered via the foot pedal mouse, the computer audibly repeats the data so patients can hear it.

Florida Probe has three systems available for unassisted data collection, with the latest being VoiceWorks, seen in Figure 1. This is a voice-activated system that is easy to voice-train, easy to use in a noisy dental environment, and has a nice feature of being able to jump back to record data such as “delayed bleeding on No. 2 – distal” with a voice command. The GoProbe System enables clinicians to use their own probe, but with a compact keypad that can be worn on the arm, and data can be entered and transferred to the computer chart seamlessly. The Florida Probe System is a constant-force technology with 15 grams of pressure each measurement, and use of the automated probe removes all guesswork. No more wondering if the measurement is a 4.5 mm or 5 mm. It precisely measures pockets to 0.02 mm accuracy when placed in the pocket, and hygienists can depress a foot pedal to transfer the data automatically to the periodontal chart. All Florida Probe systems are audible so that the patient and clinician have the benefit of hearing the data as it is being recorded, and it works with all major software programs. Use of an automated periodontal charting system is a welcome game changer for clinicians and patients.

Subgingival air polishing
For years dental hygienists have laboriously and tediously scaled away soft and hard deposits from teeth using hand and power instruments, followed by polishing the teeth with a variety of abrasive pastes. While hard deposits still need to be removed mechanically with sharp instruments and power technology, removal of plaque biofilm can now be accomplished with low-abrasive powders and air polishing devices so that biofilm above and below the gum line can be safely and comfortably obliterated. The timesaving potential of subgingival air polishing is substantial compared to removing biofilm with curettes and ultrasonics in periodontal pockets. How much would your care be altered if you had an extra 10 minutes per appointment?

Subgingival air polishing technology is not uncommon in Europe where it was developed, and it is currently gaining traction in North America. Hu-Friedy EMS has portable and countertop devices that are specifically designed for use with low-abrasive powders, with a nozzle design that’s been proven to remove biofilm coronally and in shallow pockets up to 4 mm. It also has a flexible nozzle tip that targets biofilm in deeper pockets, as seen in Figure 3. In addition, this technology can use sodium bicarbonate powders, when desired, for stain and biofilm removal on enamel.

Acteon Satelec also has a portable device with interchangeable powder chambers and nozzle tips to accommodate coronal or subgingival air polishing. Coltene has a countertop unit designed for both coronal and subgingival air polishing. Low-abrasive glycine powder has shown to be safe for use on exposed root surfaces, esthetic materials, implants, and in periodontal pockets. There is a wide variety of high-speed evacuation tips available from manufacturers that effectively manage the aerosol spray, making this game changer comfortable for patients and clinicians.

Salivary diagnostics
Saliva is a potent vehicle to maintain homeostasis in the oral cavity, but it also provides valuable information to assist clinicians in customizing care for patients.
Identification of the presence of, as well as the threshold level of, pathogenic bacteria has the potential to guide clinicians to earlier intervention and determine the need for adjunctive antibiotic therapy. Sharing salivary diagnostic information with patients’ physicians can also assist in co-management for patients with other chronic illnesses.

OralDNA Laboratories provides the MyPerioPath test, which identifies the type and concentration of specific periodontal pathogens using a sample of the patient’s saliva. A corresponding report is provided based on DNA information to help clinicians make clinical decisions for therapy and maintenance, as seen in Figure 2. Identification of destructive pathogens such as P. gingivalis and F. nucleatum are sometimes the deciding factors regarding when to provide nonsurgical treatment in otherwise borderline cases. Repeating the pathogen test following therapy ensures pathogens are eliminated or well below the threshold level, and along with the absence of clinical signs of infection, these serve as objective end points for therapy.

Approximately 30% of the population appears to have a genetic predisposition to periodontal disease, and approximately 50% of the variance in disease progression is related to an overexpression of genetic markers such as Interleukin-1 (IL-1). Therefore, identifying whether or not a patient possesses a heritable increased risk for periodontal destruction guides clinical decisions of when to treat, when to refer, and provides motivation for patients to reduce risk factors. For example, a patient that has prediabetes and is IL-1 positive has a greater risk of periodontal destruction than a patient that has prediabetes and is IL-1 negative. A patient at higher risk could benefit from more frequent preventive care even before signs of periodontal disease are present. OralDNA Labs provides the MyPerioID genetic test for Interleukin-6 (IL-6), and Interleukin Genetics provides the PerioPredict genetic test for IL-1. Some insurance companies have started using the results of genetic testing of IL-1 to correlate to intervals for preventive care.
Salivary diagnostics are also in place to identify HPV infections from OralDNA Labs, and a new test called SaliMark by PeriRx identifies biomarkers for oral squamous cell carcinoma. Salivary diagnostics are game changers that are ever changing as more information is gleaned from our patients’ saliva samples.

Topical antioxidants
Never before has there been a product with such a wide variety of clinical applications as that of topical antioxidants. Due to the ability to reduce oxidative stress and inflammation and help promote healing, topical antioxidants have been shown to be beneficial for xerostomia, management of geographic tongue, lichen planus, osteonecrosis of the jaw, peri-impantitis, gingivitis, periodontal infection, aphthous ulcers, nicotinic stomatitis, post-radiation treatment, and post-surgical healing. Data and clinical case studies also indicate that topical antioxidants may have a potential role in the prevention of conditions such as oral cancer and other inflammatory conditions in which increased oxidative stress is a factor.

Blazing the trail in the area of topical antioxidants is the company PerioSciences, Inc. Their signature product is an antioxidant gel that is applied directly to oral tissue and mucosa. They have also launched toothpastes and mouth rinses that incorporate natural antioxidants, as seen in Figure 4. Rather than a single antioxidant providing therapeutic benefit, these products combine various antioxidants — such as phloretin and ferulic acid — that possess a synergistic effect, along with essential oils that provide antibacterial activity. Periosciences has oral care kits that combine AO ProVantage topical antioxidant gel with mouth rinses and toothpastes that target a variety of conditions such as sensitivity and xerostomia. Topical antioxidants do not substitute the need for natural antioxidants from the diet or even supplemental antioxidants when indicated, but rather target specific inflammatory conditions inside the oral cavity, and can easily be incorporated into treatment protocols.

Another company that features antioxidants in their debriding mouth rinse and serum is Triology. The various antibacterial agents and antioxidants reduce pathogenic bacteria, and when the serum is applied to diseased pockets, it creates a microfoaming action to help flush out bacteria and soothe the tissue.

A significant game changer for me has been the replacement of chlorhexidine rinse with topical antioxidants, which have a noticeable pro-healing effect minus the impact of staining or supragingival calculus accumulation.

Prophylaxis whitening
What percentage of your patients wish their teeth were noticeably whiter when they leave the dental office following a prophylaxis, or even a periodontal maintenance appointment? This category of game changers I call “prophylaxis whitening” based on the fact that dental hygienists can now incorporate whitening procedures directly into their preventive appointments with very little time required. POPWhite has launched a whitening prophylaxis paste called POPWhite with a unique violet-dye composition called Viocin. When applied as a paste to discolored teeth, the violet counteracts or helps to cancel out the yellowish hues. The Viocin technology is also available in a take-home whitening kit and in a mouth rinse, with toothpaste soon to follow.

In keeping with the idea of whitening within the context of a routine dental hygiene visit, Philips Zoom launched a novel 5-minute whitening varnish called QuickPro, as seen in Figure 5, that can be applied to patients’ teeth at the end of their prophylaxis visit. The process involves a two-step technology using a 20% hydrogen peroxide gel, which is applied and then sealed with a varnish that hardens on the tooth surface. Patients are able to leave the dental hygiene appointment with the QuickPro whitening varnish having dried on their teeth. After 30 minutes, the patient brushes the varnish off and has whiter teeth. Philips Zoom and other companies also provide whitening pens for touch-ups, but being able to include a whitening treatment in the dental hygiene visit could be just the game changer needed to motivate patients to keep their appointments!

These five game changers have the potential to shift some of your paradigms, customize care to your patients, and enable you to practice more comprehensively and efficiently. So, what are you waiting for?

About the author:
Karen Davis, RDH, BSDH, is the founder of Cutting Edge Concepts, an international continuing education company, and practices dental hygiene in Dallas, Texas. She is an independent consultant to the Philips Corp., Interleukin Genetics, and Periosciences, and she serves on the review board for

January, 2015|Oral Cancer News|

Why the FDA Needs to Start Regulating Lab Tests

Author: Merrill Goozner

The Food and Drug Administration’s proposal to regulate the accuracy of laboratory-developed tests has drawn heated opposition from the laboratory testing industry, hospitals and most medical specialty societies. Only oncologists favor tighter oversight.

It’s not just cancer docs who should be concerned. We’re entering a new era where there will be much more genetic testing. Higher standards are necessary. 

Since 1988, routine laboratory tests performed inside labs have come under the Clinical Laboratory Improvement Amendments, which has largely exempted them from FDA oversight. Only if a company sold test kits to hospitals or physician offices did the FDA regulate them as medical devices, with attendant performance and manufacturing standards.

Until recently, this didn’t present much of a problem. Most lab tests are fairly routine—testing blood for cholesterol, sugar or sodium, for instance. A robust industry dominated by large national companies like LabCorp, Quest Diagnostics and ARUP Laboratories provides a market-based solution for ensuring those tests are affordable and high quality. 

Hospitals and physician offices that conduct their own in-house tests benefit from the exemption, too. Some large institutions that operate their own labs save money because of their economies of scale. Major academic medical center labs operating under CLIA also play a leading role in developing new tests for rare or hard-to-treat conditions.

But in recent years, there has been a proliferation of new tests based on genetic information that are being marketed by independent firms making claims that have not been validated by clinical trials or other scientific methods. They claim to show a person’s propensity to develop cancer or Alzheimer’s disease. The FDA has approved several new cancer drugs aimed at specific genetic mutations, and simultaneously approved the companion diagnostics needed to identify those mutations.

When companies market tests that have not been scientifically validated, it can lead to unnecessary spending and poor outcomes. Five years ago the Journal of the American College of Cardiology published a study debunking claims that a widely used test produced by Celera Corp. (founded by human genome pioneer J. Craig Venter) was able to identify people with a specific genetic mutation who were more at risk for heart attacks and would be more likely to benefit from taking statins.

An accompanying editorial by Drs. Eric Topol and Samir Damani at the Scripps Research Institute warned that the “story should serve as a valuable reminder of the potential pitfalls present in prematurely adopting a genomic test without sufficient evidence.”

More recently, actor Michael Douglas’ announcement that his bout with throat cancer had been caused by oral sex set off a marketing frenzy by HPV test manufacturers to dentists. They say the HPV test will aid in early detection and help prevent some of the 7,600 oral cancer deaths in the U.S. each year.

Given that only nine of 200 strains of HPV are associated with cancer and only one of the nine is associated with throat cancer, it would be nice to know if these tests identify the correct strain. 

No one wants to see incumbent labs and test makers use tighter regulation to prevent competition. The presence of the BRCA1 and BRCA2 genes as risk factors for breast cancer has been well-validated by science. The U.S. Supreme Court’s 2013 ruling that Myriad Genetics’ patents on those genes were invalid opened the door to numerous companies offering the test at lower prices. Would a requirement that they validate tests before marketing them really have stopped those companies from entering this lucrative field? 

The FDA doesn’t have legislative authority to regulate in-house lab tests, a fact seized on by opponents of its draft guidance who know the current Congress will not pass new legislation. The American Clinical Laboratory Association, the industry’s trade group, hired legal heavyweights Paul Clement, the Bush administration’s solicitor general, and Laurence Tribe, Harvard’s renowned constitutional law scholar, to guide the opposition.

A better course would be for opponents to work with the agency to come up with reasonable oversight standards. Medical practitioners and the public deserve protection from test purveyors making unproven claims.


*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
January, 2015|Oral Cancer News|

Study finds Oral HPV Infection Lasts Longer in Older Men

Author: Staff

FRIDAY, Jan. 9, 2015 (HealthDay News) — One type of oral HPV (human papillomavirus) infection, HPV16, seems to last a year or longer in men over the age of 45 than it does in younger men, new research indicates.

HPV16 is the form of HPV often associated with the onset of head and neck cancers (oropharyngeal), the study team noted.

“Oral HPV16 is the HPV type most commonly found in HPV-driven oropharyngeal cancers, which have been increasing in incidence recently in the United States,” said study author Christine Pierce Campbell in a American Association for Cancer Research news release. She is an assistant member in the department of Cancer Epidemiology and Center for Infection Research in Cancer at the Moffitt Cancer Center in Tampa, Fla.

“We don’t know how long oral HPV infection must persist to increase risk for head and neck cancer,” she added, “but we assume it would be similar to cervical infection, where it is generally believed that infections persisting beyond two years greatly increase the risk of developing cervical cancer.”

The study was released online on Jan. 9 in Cancer Prevention Research.

The researchers analyzed four years of samples from more than 1,600 men. The samples were collected every six months.

During the study, 23 men had two or more positive oral HPV16 samples. Of these, 10 had HPV16 when the study began.

In the group that had HPV16 at the start of the study, nine had infections that lasted a year or more. Additionally, the researchers found that eight of these infections lasted two years or more, and two lasted four years or more, the researchers found.

In those who developed infections during the study, the team found that infections in men older than 45 all lasted one year or more. By contrast, just half the infections among men 31 to 44 years persisted for one year or longer. And none of the infections detected among men 18 to 31 years lasted for a year, according to the researchers.

“Our results show that some oral HPV16 infections persist in men for four years or more and that persistence seemed to increase with age,” Pierce Campbell said.

She also noted that genital HPV infections usually clear up in two years or less. This study’s findings suggest that oral infections may be more persistent than genital HPV.

More information

For more information on oral HPV, visit the The Oral Cancer Foundation.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
January, 2015|Oral Cancer News|