The American Dental Association’s Failure to Look at the Data Critically on Oral Cancer and Bush Biopsy

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. 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.

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” 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” in the studies, 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. 

Actress Colleen Zenk Pinter becomes an Oral Cancer Advocate

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 250 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

ADA Oral Cancer Awareness Program’s Message Misses The Mark

With money from a commercial enterprise, the ADA is beginning a three year campaign to raise oral cancer awareness. This is a good thing, but the problem is they are using that company’s marketing rhetoric instead of good science to sell the message. The message of the new ads is “We can prevent oral cancer,” taken right from Oral CDx’s marketing literature.

Under that tongue (picture above) is a squamous cell carcinoma, oral cancer. (The whitish lesion, not the dark spot which is just vascularization near the surface of the tissue). If your dentist or hygienist does a brush biopsy / brush cytology of that spot, I guarantee you that it will still be oral cancer. They have not “PREVENTED” anything by doing this. It is what it is. The ADA has made a huge mistake here in their new awareness program by allowing the marketing rhetoric of a commercial company, in this case Oral CDx, dictate what the awareness program is all about. When the ADA adopts this stance they weaken their stature and look like an organization that only is interested in raising awareness of oral cancer and its early detection when someone else is willing to pick up the tab. It is the triumph of marketing over science.

This is the second time they have done so with this commercial company, the first was in 2001 when CDx gave them 2.5 million dollars to run a billboard campaign that no one remembers. Hey, I’m a big believer that when the tide comes in all boats rise, and because of that, at least part of this program is a good thing. The words oral cancer and early detection are getting out there in the same sentence to an American populace that hasn’t even heard of the disease for the most part, let alone the need for early detection of it. But oral cancers are NOT like colon cancer that requires a polyp to exist before it can become full-blown cancer. Or cervical cancer that requires an HPV infection prior to the development of a malignancy. To compare using brush cytology in the mouth, of visible lesions, to either of those is wrong. There is no “mandatory” oral precancerous lesion that always appears before manifestation of this disease. Many times even the primary disease itself can be occult and not visible, only detectable early through the palpation and touching of the tissues - feeling for indurations or hard spots, or in some cases the primary lesion is completely occult right up until a metastasis of the disease is discovered as an enlarged lymph node in the neck, and the primary is never found. A brush biopsy does not prevent this disease.

Let’s say you have a leukoplakia under a tongue. It’s a huge thing - like half and inch long and three eights of an inch tall. Only about 25% of the time do these things go over to the dark side and become malignant. But they need dealing with (removal) or regular monitoring by a professional (less desirable in my opinion). With a brush biopsy you have to SCRUB the suspect tissue to the point of bleeding to get the proper collection of cells. Is a dentist going to do that over a lesion the size I just described? Hardly. And there is no way to tell where in that large lesion a group of cells that is going malignant might reside. Given this, you couldn’t just collect a few cells from the front or the back of it. Brush biopsy in this case is probably not the path to go down. You could have an oral surgeon laser off the whole thing, or you could watch it for changes (less desirable idea), because only a quarter of them actually become malignant.

The gold standard for diagnosis of cancer is a conventional punch or incisional biopsy. It gives you a core of tissue (if done with a small punch), and all the stratum of the different layers of cells intact. This is an important issue to a pathologist looking at that sample. Brush cytology gives you scrambled eggs… you don’t know where in the total thickness/layers of the tissue the cells scrapped off with the brush came from. Even Oral CDx literature says that if you get a positive test result from them, you have to have it confirmed with a conventional biopsy anyway. If that is the case, generalists who are uncomfortable making the call should let the oral surgeon, oral medicine specialist, etc. make the call to biopsy or not when the patient is sent to them for a second opinion of any suspect tissue.

I get it that this idea is to keep dentists from watching and waiting while a potential malignancy develops in the mouth, because this has been a problem with things for some time. Actually that has been a smaller problem than the fact that not enough dentists are actually doing opportunistic screenings on their entire patient populations at all. This brush system has been around for years and it has not won a place in dentistry in all that time. The fact is, that a general dentist, when he finds suspect tissues, is better served by sending that patient for a second opinion to an oral surgeon or especially to an oral medicine specialist (they are usually not in private practice but at institutions like dental schools) than messing around doing an indeterminate brush biopsy. Dentistry has a well established referral system, and with the potential of a cancer prospering un-referred on their watch, which is deadly for the patient, and exposes the dentist to significant legal liability, this makes the most sense.

As a patient I have learned that several sets of eyes, and differently trained minds with different types of clinical experience, yield the best end result when deciding what something is, or what should be done.

It is disappointing that the only time the ADA wants to get into the fray and try to do something in the oral cancer arena, it requires someone else to pick up the tab to get them interested. The oral cancer insert in their magazine JADA several years ago was paid for (in spades) by outside organizations like NYU, OCF, the NIDCR and others, the last billboard awareness campaign in 2001 with an equally off the mark marketing tone from CDx which stated “Don’t let it grow up to be cancer” was paid for by someone with a product to push, and now this. Of course their charter is not necessarily to help the public. They are a professional association to serve the interests of dentists, not the public.

As a side note, how is it that the Oral CDx brush bears the ADA seal of approval as a product, yet in the ad using it as the means to change the world, the ADA says they do not endorse the product? Someone didn’t think this through very well. Perhaps if someone like CDx was offering me 9+ million dollars to do something (as they have with the ADA), I might rush into it as well….

Researcher Maura Gillison: Completely Changing the Playing Field of Oral Cancer Screening

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.

Finding oral cancer early is the key

This poster is from the US Government printed in 1938. We have known about the necessity for early detection for a long, long time....

NEWPORT BEACH, Calif., Nov. 20 /PRNewswire/ -- The Oral Cancer Foundation announced today that three researchers working in areas of early oral cancer detection would be the foundation's first grant recipients.The grants, which were made as an ongoing commitment to each researcher, were awarded to Dr. Maura Gillison of Johns Hopkins School ofMedicine, Dr. David Wong of the University of California at Los Angeles, and Dr. Ann Gillenwater of the University of Texas MD Anderson Cancer Center. "We are supporting research that moves our early discovery agenda forward," the foundation's executive director Brian Hill said. "Early detection is our first front in reducing the death rate from oral cancer, and we believe these research programs all will have a huge impact on how and when people are diagnosed with the disease.

Early detection and staging is directly correlated to better long-term outcomes for patients. "The disease affects more than 34,000 Americans each year, and more than 8,000 will die from it annually. At the present time two-thirds of cases are caught in the cancer's later stages when prognosis is poor. At 5 years from diagnosis survival for all stages combined is approximately 50%. While other cancers have seen a decline in incidence and death, occurrence of oral and oropharyngeal cancers have increased in recent years, 11% in 2007 alone. "Public awareness of the disease is low, and screening models used incorrectly or inconsistently are largely to blame for the high death rate," Hill said. "We could be doing a better job of early discovery. Patients need to know that an annual screening is inexpensive, painless, and takes only five minutes. But the lack of awareness-in both the health care community and the public's mind-of the newly defined viral etiology of oral cancer is now also to blame."Oral cancer has been most usually associated with tobacco use, often in combination with alcohol consumption. However, new research over the last decade has pointed to the human papillomavirus (HPV-16), the same virus that causes the vast majority of all cervical cancers, as a significant risk factor, especially in cases affecting young non-smoking men and women.

Grant recipients.

Dr. Maura Gillison

Maura Gillison, MD, PhD, assistant professor of epidemiology of Johns Hopkins School of Medicine, merited headlines across the globe for her research on the role the HPV virus plays in the etiology of oral cancer, and without ambiguity defined the link between the two. Her work has changed the demographic norms for those previously considered at risk for the disease, and has broad implications for developing preventative measures for HPV-positive patients and treatment options for oral cancer patients with HPV-derived cancer.

Dr. David Wong

David Wong, DMD, DMSc, director of the UCLA Dental Research Institute, is a nationally recognized expert in the emerging field of salivary diagnostics. Wong's work will yield an accurate, noninvasive test for very early detection of oral cancer, and likely other high-impact systemic diseases within a few years. It is the first viable option for conducting mass public screenings for oral cancer using only a small amount of saliva and a computer chip which looks for specific biomarkers. Given the shift in etiology of oral cancer cases away from the obvious potential patient identifiers like smoking to the less easily detectable virus, Wong's research will be instrumental in identifying those most at-risk for the disease.

Dr. Ann Gillenwater

Ann M. Gillenwater, MD, associate professor, department of head and neck surgery, the University of Texas MD Anderson Cancer Center, has been part of a pioneering team in the use of tissue fluorescence as a discovery tool in oral cancers. Tissue fluorescence, in which a specific spectrum of light is used to differentiate healthy cells from those which are not, will allow the health care professional to identify more readily areas of suspect tissue that may be missed in a conventional white light visual screening. This will improve the opportunity for early diagnosis, thus improving patient outcomes.

The Oral Cancer Foundation, a 501(c)3 non profit charity, founded in 2000, advocates for better public awareness of the disease, provides patient support mechanisms, and engages the medical and scientific communities to be more involved in the process of early detection. The foundation conducts screening events across the country and maintains a web site with hundreds of pages of information for patients, the public, and healthcare providers at http://www.oralcancer.org.