The Oral Cancer Advocate

2007 ADA ad compares brush test to others. (They got it half right….)

You would think that an organization that is made up of doctors would get things right. Let’s start with the misrepresentations in their current advertising campaign about early detection of oral cancer using a brush biopsy system, more commonly known as brush cytology. In my previous postings I have stated that one of the main features of their awareness campaign that is wrong, is that it bypasses the initial requirement of discovery. But now that some of the really knowledgeable people (from the world of science and research) have looked at this, more has come to light.

First, in the ads it shows a specificity and sensitivity in the 90 percentile, with the initials NCI next to it. The numbers did not come from the NCI, nor have they evaluated this system according to calls made to them. (Shall we call this a misprint…or should we just say it is fraudulent advertising? Perhaps this really doesn’t stand for The National Cancer Institute, but actually means not correct information…) The numbers actually come from a study funded by Oral CDx in Germany by Christian Scheifele et.al. How the ADA or anyone else who put this ad together ties that article, which was published in an Elsevier journal, to the National Cancer Institute is very unclear, and perhaps even deceiving. (Note: I have cut off the bottom portion of the ad that shows this copy from the ad above to fit the picture in the alloted space.)

To restate the obvious, since its use began in the 1920′s brush cytology, or if you want to use the branded term “brush biopsy” from many companies, and now from CDx, has had specificities and selectivity numbers in the 50-60 percentile range. I guess you would have to ask yourself how something, that in numerous studies showing this, would suddenly leap into the 90 percentile level. Actually, it just a matter of poor study design. When CDx did their studies, as a prelude to their marketing campaign, they included in them both class I and class II lesions.

If you are not familiar with what this means, in the simplest of terms, a class I lesion is advanced to the state that your suspicion that it is cancer is high. It is an open ulceration, it is bleeding, it is cratered, etc. it has characteristics that send lights and bells going off in your head when you look at it. In short your paperboy could look at it in your mouth and guess that it was something dangerous and likely malignant. The CDx system is NOT designed to be used on class I lesions, they say so themselves, and were it used in that manner, the person doing so would be doing the patient a disservice as well. Anything that obvious needs to be biopsied using a gold standard technique, not a brush. Class II lesions are small, and early developments that it would be hard for anyone to visually determine that they were something benign, or dangerous. This is what the Oral CDx brush is designed to evaluate.

But if you look at the company sponsored studies carefully, you see that they include in the lesions evaluated, a significant number of class I lesions. It would be one thing if these were used as a “control” but they are not. They are lumped in with the class II lesions. What happens to the numbers if you take the class I lesions (which without testing visually scream “I’m dangerous”) out? The specificity and sensitivity of the CDx system goes right back to where you would expect to find it… in the mid 50% range. Right where brush cytology has always been.

The ADA is counting on the fact that the public does not understand all this, and for that matter, I bet the bulk of the general dental professional population does not either. That the ADA has rushed into all this without looking carefully at the data, (after all, this is not their first dance with Oral CDx, they did a similar billboard campaign in 2001 with the company)without consulting recognized experts in the field, has put their logo on what is nothing more than a misleading advertisement from a product manufacturer; because they are either too lazy, or lacking the ability to design their own program, or unwilling to spend their own money on it, is really pathetic. The more I look at this the more it stinks. Yes, oral cancer and detection are getting out there in the media, but the message is wrong. I wonder when the dental community is going to pay attention to this and ask their professional association to discontinue this money-motivated ruse, or to at least quit rubber stamping the commercial company’s marketing program, and put out ads that state this in a scientifically correct manner. At least this current ad that I saw didn’t say “We can prevent oral cancer.”

I have said it before and I say it again. You wish to bring the death rate down from oral cancer it is through early discovery…. This program is based on diagnosis, and talks little about the most important component, opportunistic screening of dentist’s entire patient populations where early discovery will take place. No opportunistic screening = No early discovery = Nothing to biopsy with the brush or anything else. The message is FIRST about getting screened guys; eyeballs, fingers, ancillary devices, by a non complacent group of professionals. THEN it is about diagnosis.

As for the ADA, who clearly has not paid attention to debacles that have impacted other organizations in their league, I only have one final comment – Think of the AMA and the Sunbeam company. History is a hellava teacher if you pay attention.

Tags: Adjunctive Screening Devices, Screening, The ADA by oc advocate
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Since her article on the relationship between HPV and oral cancers, published in 2000 in the Journal of The National Cancer Institute, the work done and published by Dr. Maura Gillison and her colleagues at Johns Hopkins has redefined the demographics of the oral cancer world in the US. While I have read many researcher’s work, I am really impressed by the series of publications from Dr. Gillison that have elucidated the oral cancer – HPV relationship in ways which are not just interesting, but which have direct applications in reducing the death rate from the disease today. What I am referring to is early detection.

The first rule in solving a problem is defining reality, that is, “what is the situation right now”? If professionals are to be effective in finding disease at the earliest possible stages when outcomes are the best, we have to understand WHO is at risk, and by doing so, who needs to be screened as a matter of routine. Her work has revealed a sub population of young, non-smoking individuals that no one was considering to be at risk, and by doing so changed everything. Being a non-smoker is no longer enough to allow you to dodge this disease. A virus is increasingly becoming a major factor in young people who develop oral cancer. Dr. Gillison’s epiphanies turned into proof of principal studies, and finally peer reviewed published articles that reveal how, with little control over the circumstances related to exposure available to us, we can do little to ensure that we are not at risk for developing this cancer. HPV is a ubiquitous virus, plentiful in the world around us, and easily contracted. For that matter, the CDC says that likely 80% of the US population will have at least one of the more than a hundred versions of HPV at some point in their lifetime. What we do not know is how many will get an oncogenic version of it, and of those, how many will go on to develop cancers.

Determining who was at risk used to be easy in the world of dentistry (doctors of general medicine have never been educated well in finding early stage oral disease). There were historical models that dentists were taught in school about the “typical” oral cancer patient. They were in their sixth and seventh decade of life, they had been tobacco users for at least a decade of their lives, used alcohol, were more frequently men, and more frequently black. But for the last several decades major treatment centers all around the US have anecdotally reported that they were seeing more and more young, non-smoking, white, under 50 year old patients with oral cancer. These people didn’t fit the historical demographic. Of course for the most part, with the exception of dentists working inside the cancer treatment centers, this information was not on the radar of most dental professionals. When they did screen, they thought of the older smokers. Notice that I said, when they did screen. Articles published by Horowitz et. al. from the NIH/NIDCR clearly showed that dentists have not been doing a very good job of engaging in actively screening their patients and finding disease at early stages. While there has been some improvement, things in the dental screening world are just starting to turn around in regard to screenings being done with any regularity. The quality of the screenings still remains to be evaluated. Medicine is even further behind the curve in all this.

Along comes Gillison and her articles. This really throws a wrench in what dentistry has considered the typical patient. Now they have to screen just about everyone that comes into their practice; because HPV16 has been shown through these articles to be a significant and unique (from tobacco and alcohol) pathway to oral cancer. She has defined the anatomical locations in the mouth it has a preference for (no excuses about where to look), she has defined in additional articles that it is easily transferred through oral and conventional sex, and she is telling us who the new demographic is – that is completely unlike the historical stereotype.

My question is – why is dentistry so far behind the curve over the last 7 years as this data has been revealed? Actually, I am being kind to the profession here, since their lack of interest in OC screening and early detection goes back decades, as does that of their professional society, the ADA. One excuse would be that these articles have been published in medical and oncology journals, and the general population of dentists seldom read these. But it is time that the work of this researcher becomes mandatory reading for the dental professional population. She has changed the understanding of the etiology of OC, and with it, who must be screened. My guess is that we will see HPV become THE dominant cause in young oral cancer patients, and the old 75% from tobacco cause is grossly out of date when considering this group.

Read the New England Journal of Medicine article that broke through the usual “research isn’t big news” apathy of major media because oral sex was part of the description… gillison_nejom_2007.pdf.

Tags: HPV, Screening, The Changing Demographics by oc advocate
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The Oral Cancer Foundation has partnered with yet another celebrity to help get the word out about oral cancer. They clearly understand the power that TV and movie personalities bring to raising public awareness, the first essential component to bringing the death rate down. Ms. Pinter is in good company with other OCF partners – three-time Emmy winner Jack Klugman, and two-time Emmy winner and Tony winner Blythe Danner (Gwyneth Paltrow’s mom for those who do not follow these kinds of things). Anyone reading my postings to date and looking at my links, can tell that I am a fan of OCF’s work. The only thing I do not get, is why they do not capitalize on these celebrities to help them raise funds. Clearly as a small non-profit charity they can’t be bringing in the kind of donations that the big guns like the American Cancer Society and the breast cancer folks do. Someone who is in a financial realm which I do not personally inhabit needs to look at these guys. They get more done for less than anyone else out there. What could they do if they had some financial support? Anyway, what follows is their press release on this relationship.

Actress Colleen Zenk Pinter Partners with the Oral Cancer Foundation to Raise Public Awareness

Two time Emmy nominated actress Colleen Zenk Pinter, best known for her long running role as Barbara Ryan on CBS’s As the World Turns, has teamed up with the Oral Cancer Foundation to share the story of her battle against oral cancer, and raise public awareness of a disease which kills more Americans each year than more commonly known cancers.

Zenk Pinter’s first stop was CBS’s The Early Show. In an interview with co-anchor Hannah Storm, Zenk Pinter revealed how a seemingly stubborn canker sore turned out to be a stage-two malignant oral cancer, requiring several surgeries to reconstruct her tongue, and months of radiation treatments. Zenk Pinter explained to Storm that she believes that her cancer was caused by the human papillomavirus. “I had absolutely none of the historic risk factors for this cancer, I never used tobacco and only drank socially,” she said, referring to the two other common causes of the disease.

“In fact, young Americans who have none of the historic risk factors are the fastest growing segment of oral cancer patients in the country,” Brian Hill, executive director of the Oral Cancer Foundation says, “and we believe the culprit behind the surge in cases is HPV16, the same virus that causes cervical cancer.”

Dr. Mark Lingen, Professor of Pathology at the University of Chicago School of Medicine says, “Colleen was very typical of most Americans in their lack of knowledge of oral cancer. Awareness and routine screening is particularly important, since early discovery is directly correlated to positive outcomes from treatment. HPV is the most common sexually transmitted disease in the United States. At least 50 percent of American adults will acquire the virus at some point in their lives. HPV16, one of the most destructive strains of the virus, was definitively linked to oral cancer in 2001. Research has also established that the virus, which can easily be transferred, may even be a more significant risk factor than tobacco in the younger portion of the population.”

“Colleen is an amazing woman”, said Hill. “Even BEFORE she had begun her treatments for the cancer, she contacted me and wanted to become an advocate for early detection and increased awareness. She was clearly taken by surprise to have developed this cancer. Most people at that point in the process are only thinking of themselves, and getting through the really tough treatments successfully. Her willingness to talk publicly about her very personal and painful battle with oral cancer is certainly courageous, and the desire to help others is palpable when you speak with her. Her story and high profile celebrity as a well-known TV actress will have enormous impact educating the public about this deadly and disfiguring disease. This is one of the purest examples of altruistic, celebrity power being used to better other people’s lives. We are lucky to have this partnership with Colleen.”

Now cancer-free, Zenk Pinter urged viewers of The Early Show to get regular oral cancer screenings. “Your dentist should be doing an oral cancer exam at every visit,” Zenk Pinter said. “It’s a simple 5 minute, painless exam that may save your life.”

The Early Show was only the first of what is on the public awareness schedule for Zenk Pinter. A recent interview with Soap Opera Digest is already on the newsstands, and interviews with other magazines have been scheduled. In December she will film a TV Public Service Announcement on the need for early detection through annual screenings. OCF will distribute the PSA to TV stations across the country at the beginning of 2008.

About Colleen Zenk Pinter
Ms. Zenk Pinter has worked professionally since the age of nine as an actress. Besides her long time association with As the World Turns, in which she has appeared in over 2,000 episodes, Colleen made her Broadway debut in Bring Back Birdie. Her film debut was in John Huston’s adaptation of Annie. Her benevolent and philanthropic association with health causes is not new, and for decades she has donated time to work with the Easter Seals, the March of Dimes, the Cystic Fibrosis Foundation and Bread to Roses, one of the first AIDS hospice programs. For more information about Colleen’s background, go to http://www.astheworldturns.net

The Oral Cancer Foundation, founded in 2000, is a national non-profit charity based in California. The foundation advocates for better public understanding of the disease and engages the medical and dental communities to be more involved in early detection. The foundation maintains a Web site with information for patients, the public, and health care providers at www.oralcancerfoundation.org. It is supported through tax-deductible public donations which can be made at http://www.oralcancerfoundation.org/membership/membership.htm

Tags: Oral Cancer News by oc advocate
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What follows are some interesting works involving berries and cancer. Please note that while some of this is very interesting, it is a long way from being something that can be applied usefully today. These are very preliminary looks at things, and I put thm up on the blog to let people know some of the novel trains of thought people are pursuing. While it won’t hurt you to eat a ton of berries, and it certainly would be healthy, the evidence does not support a proven idea that you should suff yourself with these tasty fruits to do more than eat a nutritious food for your body. At this point in time whether there is any efficacy for them in relationship to cancer in humans is still a quuestion. But it’s, berry, berry interesting….. ( I can’t believe that I just typed that lame play on words.)

Dark fruits like blueberries, blackberries as well as papaya could be used to stop mouth cancer cells spreading through the rest of the body. They could also reduce the risk of mouth cancer, according to research published in the Journal of Cancer Research.

The study, carried out at the University of Hong Kong, found that as well as suppressing the spread of cancer, a substance called lupeol found in blueberries and other “super fruit” also reduced the size of the tumour three times faster than conventional drugs. When the two were used together they were even more successful. The compound works by blocking a natural protein called NFkB which helps to grow and repair all cells – even cancerous ones. Tests on mice also suggested that, unlike conventional drugs, lupeol would not cause the patient to lose weight.

Dr Nigel Carter, chief executive of the British Dental Health Foundation, said, “We already knew a healthy diet, including at least five portions of fruit and vegetables each day, could reduce a person’s risk of developing mouth cancer. “However the news that certain fruits might help to combat mouth cancer in people who have already developed the condition is a real revelation. “It is true that this research is still in its early stages. However, the suggestion is the lupeol compound could be more effective than traditional drugs in preventing the growth of mouth cancer cells.”

In anothger study, Ohio State University researchers found black raspberries may protect against esophageal cancer by reducing the oxidative stress that results from Barrett’s esophagus, a precancerous condition usually caused by gastroesophageal reflux disease. Reflux disease causes stomach acid to continually splash back up into the esophagus.

“Specifically in the case of Barrett’s patients, reflux of the stomach and bile acid contribute to ongoing oxidative damage. Thus, our hypothesis is that feeding a food that is high in potential protective constituents, such as antioxidants, vitamins, minerals and other phytochemicals, may help restore the oxidative balance,” lead researcher Laura Kresty said. People with Barrett’s esophagus typically are 30 to 40 times more likely to develop esophageal cancer, which has a poor five-year survival rate of 15 percent.

The team gave 32 grams to 45 grams of black raspberries daily for six months to 20 patients with Barrett’s esophagus. They analyzed changes in blood, urine and tissue before, during and after the treatment, and found lower levels of some of the chemical markers of oxidative stress in both urine and tissue samples. Black raspberries previously have been shown to reduce the risk of oral, esophageal and colon cancer in animal models, according to the researchers, who called for further study in humans.

Ohio has another take on berries as well. Gary Stoner, PhD, a scientist at the OSU Comprehensive Cancer Center – James (OSU CCC-James) who has spent years conducting food-based cancer-prevention studies, says one serving should involve black raspberries, blackberries or strawberries. Stoner and colleagues have found that all three exhibit anticancer properties in rodents, but their more extensive studies have involved black raspberries. “Black raspberries have high levels of anthocyanin pigments that give the berries their color and act as antioxidants to reduce cellular DNA damage caused by oxygen radicals and carcinogens in the body,” says Stoner. “The more antioxidant activity, the more a berry can inhibit cancer.”

Stoner’s studies began in the 1980s when he examined ellagic acid, a compound that inhibits carcinogen-induced cancer in animals. Seeking natural sources of this compound, his team examined many fruits and found it most abundant in berries. They then began testing the berries’ ability to inhibit chemically induced esophageal and colon cancer in rodents. Collaborating with the OSU College of Food, Agricultural and Environmental Sciences, Stoner’s team found that freeze-dried strawberries, black raspberries and blackberries, when added to the diets of rodents, prevented carcinogen-induced esophageal cancer by 60 percent compared with rodents on normal diets. They found that black raspberries inhibited carcinogen-induced adenocarcinoma in the colon of rodents by up to 80 percent.

At first they thought ellagic acid was principally responsible, but Stoner says they realize the inhibitory activity cannot be attributed to just one substance. “We think other components, such as anthocyanins and other polyphenols, and the vitamins and minerals in berries, are also responsible,” he says. “Now we are trying to find out what natural compounds are the most effective cancer fighters.”

In July 2003, he received a $2.7 million, five-year grant from the NCI to examine mechanisms by which freeze-dried black raspberries prevent cancer in rodent esophagus. “The goals,” Stoner says, “are to better understand how berries block and suppress cancer activity and to develop a ‘cocktail’ of chemopreventive agents for preventing human esophageal squamous cell carcinoma.”

The berry findings were presented at the International Conference on Frontiers in Cancer Prevention Research, being held in Philadelphia, Pennsylvania.The National Cancer Institute-funded trial included 30 participants, 20 of whom had identifiable precancerous lesions, and 10 normal controls. Each of the participants was instructed to gently dry the lesion sites (or a pre-selected control site for the normal participants) and rub the gel into the area four times a day, once after each meal and at bedtime.

After six weeks, about 35 percent of the trial participants’ lesions showed an improvement in their microscopic diagnosis, while another 45 percent showed that their lesions had stabilized. About 20 percent showed an increase in their lesional microscopic diagnoses. Importantly, none of the participants experienced any side effects from the gel. “The trial was designed to test the safety of the gel and detect any possible toxicity, but the next obvious step is a multicenter, double-blind, placebo-controlled Phase II study,” Mallery said. “Such a study would enable us to determine that the black raspberries are the active factor and not just the gel base or the act of drying and rubbing the lesions.”
The researchers also collected cell samples from the lesion sites of each participant before and after treatment in order to study the genetics and biology of the lesions. The majority of patients with precancerous lesions at the start of the trial showed elevated levels of COX-2 and iNOS, two proteins closely correlated with inflammation and malignant progression. Following treatment, Mallery says, levels of those proteins in the treated lesional epithelial cells decreased dramatically.

Mallery and her colleagues also examined samples for three tumor suppressor genes in order to determine what researchers call “loss of heterozygosity,” whether or not a cancer cell has lost one of its two copies of the gene. Such loss greatly increases a cell’s chances of losing the benefit of the tumor suppressor genes due to a second mutation or gene silencing event. Following the trial, the researchers noted that many lesions returned to normal, retaining both copies of each tumor suppressor gene. “We speculate that the chemopreventive compounds in black raspberries assist in modulating cell growth by promoting programmed cell death or terminal differentiation, two mechanisms that help “reeducate” precancerous cells,” Mallery said. “Oral cancer is a debilitating disease and there is a desperate need for early detection and management of precancerous lesions,” Mallery said. “While screening can help detect the disease early — and survival rates are definitely improved the earlier the disease is caught — many of these precancerous lesions recur despite complete surgical removal. There are currently no effective chemopreventive treatments which could conceivably serve as either adjunctive or alternative approaches to surgery.”

According to Mallery, the development of black raspberries as potential cancer-fighters is the result of decades of research into identification of naturally derived chemopreventive compounds by Ohio State researcher Gary D. Stoner, Ph.D., an emeritus professor at Ohio State University’s College of Medicine and Public Health. Clinical studies stemming from his research are currently underway for oral, esophageal and colorectal cancer.
The gel looks deceptively like black raspberry jam, but it certainly does not taste like something you would want to spread on toast, Mallery says. The bioadhesive gel, which contains 10 percent freeze dried black raspberries, is devoid of many of the tasty sugars found in native berries.
The black raspberry gel was manufactured by the University of Kentucky’s Good Manufacturing Production (GMP) facility. NanoMed Pharmaceuticals is partnering with OSU investigators Mallery, Stoner and Peter E. Larsen D.D.S. and Russell J. Mumper, Ph.D., of the University of North Carolina, in product development.

Tags: Chemoprevention, Oral Cancer News by oc advocate
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