The Oral Cancer Advocate

The sexually transmitted virus that causes cervical cancer in women is poised to become one of the leading causes of oral cancer in men, according to a new study. The HPV16 virus now causes as many cancers of the upper throat as tobacco and alcohol, probably due both to an increase in oral sex and the decline in smoking, (the historically dominant risk factor) researchers say.

The only available vaccine against HPV, made by Merck & Co. Inc., is currently given only to girls and young women. But Merck plans this year to ask government permission to offer the shot to boys. Experts say a primary reason for male vaccinations would be to prevent men from spreading the virus and help reduce the nearly 12,000 cases of cervical cancer diagnosed in U.S. women each year. I might add that by not doing gender based vaccination, we will reduce the overall reservoir of the virus in the US which is currently ubiquitous in the population. But the new study should add to the argument that there may be a direct benefit for men, too. The study was published February 1, 2008, in the Journal of Clinical Oncology.

“We need to start having a discussion about those cancers other than cervical cancer that may be affected in a positive way by the vaccine,” said study co-author Dr. Maura Gillison of Johns Hopkins University. Of course she is referring the the rapidly rising numbers or oropharyngeal, base of tongue, and tonsillar cancers we are seeing in both males and females.

Human papillomavirus, or HPV, is the leading cause of cervical cancer in women. It also can cause genital warts, penile and anal cancer, and oral cancers — risks for males that generally don’t get the same attention and press as cervical cancer. Previous research by Gillison and others established HPV as a primary cause of the estimated 5,600 cancers that occur each year in the tonsils, base of tongue and upper throat. It’s also been known that the virus’ role in such cancers has been rising. It is in fact, the primary cause of cancers in these anatomical sites.

The new study looked at more than 30 years of National Cancer Institute data on oral cancers. Researchers categorized about 46,000 cases, using a formula to divide them into those caused by HPV and those not connected to the virus. They concluded the incidence rates for HPV-related oral cancers rose steadily in men from 1973 to 2004, becoming about as common as those from tobacco and alcohol.

The good news is that survival rates for the cancer (when caused by a viral etiology) are also increasing. That’s because tumors caused by HPV respond better to chemotherapy and radiation, Gillison said. “If current trends continue, within the next 10 years there may be more oral cancers in the United States caused by HPV than tobacco or alcohol,” Gillison said.

Studies suggest oral sex is associated with HPV-related oral cancers, but a cause-effect relationship has not been proven as the only viral transfer mechanism for these cancers. Other researchers have suggested that even unwashed hands can spread it to the mouth as well. Gillison however pointed toward sex as an explanation for the increase in male upper throat cancers, and her previously published work documents this in the New England journal of Medicine. In women HPV-related upper throat cancers declined significantly from 1973 to 2004.

Merck’s vaccine, approved for girls in 2006, is a three-dose series priced at about $360. It is designed to protect against four types of HPV, including one associated with oral cancer. Merck has been testing the vaccine in an international study, but it is focused on anal and penile cancer and genital warts, not oral cancers, said Kelley Dougherty, a Merck spokeswoman. “We are continuing to consider additional areas of study that focus on both female and male HPV diseases and cancers,” Dougherty said. Merck officials praised Gillison’s research, saying it will elevate the importance of HPV-related oral cancers. As I have posted here before, I believe that Gillison’s work should be mandatory reading for all those that have the opportunistic ability to discover early these very deadly posterior mouth cancers (Dentists, oral hygienists, and members of the ENT profession.)

In a typically guarded observation, Government officials and the American Cancer Society say they don’t know yet whether Merck’s vaccine will be successful at preventing disease in men. No data from the company’s study are available yet. Indeed, it’s not clear yet that the vaccine even prevents the HPV infection in males, let alone cancer or any other illness, said Debbie Saslow of the American Cancer Society. However in speaking with experts in the virus research community, I believe that if Merck’s current trials show that it can prevent persistent HPV 16 infections, that the logical extension of that fact would indicate that without the persistent infection, there would also be no mechanism for the disease process to take place. Keep in mind that tobacco will still be a major player in the incidence of oral cancers, and we are looking at a subset population of people with oral cancer when speaking of HPV16.

Merck plans to seek U.S. Food and Drug Administration approval for the vaccine in men later this year, meaning a government decision would be likely in 2009.

Tags: HPV, Oral Cancer News, The Changing Demographics 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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Does what we know about brush biopsy in cervical cancer screening have any meaning when using brush biopsy screening in a different location? The Papanicolaou (Pap) smear (brush biopsy) is commonly used to screen for cervical cancer, and since its introduction in organized screening programs in resource-rich countries it has been successful in dramatically reducing the incidence of cervical cancer. However, the sensitivity of the Pap smear is low, and so testing for DNA of the causal agent of cervical cancer, the human papilloma virus (HPV), either as an alternative or in conjunction with a Pap smear, is being recommended by the CDC.

Mayrand et al. reported the results of the first screening round of the Canadian Cervical Cancer Screening Trial, in which over 10,000 women aged 30 to 69 years were randomly assigned to receive either a Pap smear or an HPV DNA test approved by the US Food and Drug Administration to screen for high-grade cervical intraepithelial neoplasia. Women with positive test results underwent colposcopy and biopsy, as did a random sample of women who tested negative. The sensitivity of HPV testing was 94.6%, whereas that of Pap testing was 55.4%. The specificity was 94.1% for HPV testing and 96.8% for Pap smears. In a second study reported in the New England Journal of Medicine, over 12,000 women aged 32 to 38 years were randomly assigned to receive either an HPV test plus a Pap smear or, as a control, a Pap test alone. The results of this trial found also that the HPV testing was significantly more effective. A shift from cellular to viral tests, coupled with education and vaccination, will clearly contribute to more efficient control of cervical cancer.

Having this information available to us now, the ADA program on oral cancer early detection with what is essentially the same kind of brush cytology, seems misguided. The brush collection of cells is the same regardless of the type of tissue that you are collecting them from. When considering the cervix, it is a very small area and a general brushing of the area is possible. The mouth does not lend itself to such a generalized collection process because of its size, and therefore the sampling of something visible that is evident to the screener is necessary. What the ADA program needs to talk about is early DISCOVERY – without that, there is nothing to put a biopsy brush on anyway. The ADA program is all about DIAGNOSIS, which of course cannot take place until DISCOVERY happens first. They seem to have put the cart before the horse, and the emphasis in the wrong place.

One argument from the manufacturer is that the shape of the bristles on their brush are different than conventional cytology brushes, and that when rubbed against the tissue hard, (until blood appears) that they are collecting cells from ALL layers, and therefore to compare the two is inaccurate. I have spoken with several oral pathologists at two local dental teaching institutions and they are not big believers in the technique. (Granted, a very small sample.) A conventional incisional or punch biopsy still has to be sent to them if this brush system finds a positive.

Bottom line in all this is that the selectivity and specificity of the Oral CDx system seems an academic point. We do not have in the US a dental profession that is compliant in doing OPPORTUNISTIC screenings of their entire patient populations on a regular and systematic basis.

If a general practitioner of dentistry, otolaryngology, or medicine finds tissue which appears to them to be abnormal, and the patient has told them that it has existed over a period of 14 days or longer, or they recall the patient in that period and find that it still exists, I believe the appropriate thing to accomplish at that point is to obtain a definitive diagnosis of what it is. This cannot be accomplished with a brush cytology system. A positive result from this system still requires surgical biopsy. The more appropriate action would be to either do a punch or incisional biopsy should they feel competent, or better yet, to use the well established referral system to obtain a second opinion, biopsy and diagnosis. This may be to an oral medicine specialist, an oral surgeon, or otolaryngologist with additional training in head and neck surgery, who is familiar with oral malignancies and other pathologies. This not only serves the patient well by obtaining another informed opinion as to what the malady is, but it also (for those not completely conversant in oral pathologies), it ensures that any tendency to “watch and wait” will not be engaged in. This is the worst thing that can be done, and invariably leads to delayed diagnosis, and poorer outcomes for those who do have a malignancy.

This whole system only works if we have compliant screeners, something which do not exist in abundance in the US today.

Tags: Adjunctive Screening Devices, HPV, Oral Cancer News, Screening, The ADA by oc advocate
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A single HPV virus

Scientists are only beginning to discover the hidden role of some viruses and bacteria. The almond-shaped lump on Brian Hill’s throat didn’t make sense to him. The doctor said it was a symptom of advanced oral cancer, but Hill had never smoked a cigarette or chewed a plug of tobacco, considered the main causes of the disease when he was diagnosed in 1997. So why was it there? Not until four years later did Hill get an explanation for his brush with death: a microbe called human papilloma virus-16 had apparently moved into his tonsils, gradually turning normal cells into cancer. Hill, now 59, had become part of a wave of relatively young nonsmokers who contracted oral cancer from the sexually transmitted virus, fueling an overall increase in new cases.

Viruses such as human papilloma may be the most overlooked bad guys in the war on cancer, silent invaders that contribute to more than a dozen malignancies and may cause 15 percent of the cancer cases worldwide each year. “What we know about HPV-16 as a cancer causer is just the tip of the iceberg,” said Hill, founder of the Oral Cancer Foundation, which funds research for a disease that strikes 34,000 Americans annually and is caused by the same virus that can lead to cancers of the cervix, vulva, anus, and penis.

The cancer toll from germs – both viruses and bacteria – may turn out to be higher as researchers discover more of these elusive microbes and how they do their grim work. Currently, scientists can’t even estimate how many viruses afflict human beings, let alone how they impact human health. Some suspect that unknown viruses may be causing cancers that are now blamed on something else, much the way doctors believed that stress and spicy foods caused stomach ulcers until scientists discovered the real culprit – bacteria – in 1982.

“There are a lot of infectious diseases that we just don’t know about, including a lot of cancers,” said Dr. Matthew Meyerson, a cancer genetics researcher at the Dana-Farber Cancer Institute in Boston and the Broad Institute of Cambridge. Unfortunately, he said scientists have not come up with a simple way to identify unknown viruses lurking inside human genes. But it’s already clear that cancer is more contagious than most people realize: everyday acts of intimacy such as kissing and lovemaking potentially transmit viruses from one person to the next that, for an unlucky minority, will cause cancer years later as the genetic damage to cells slowly mounts. For instance, people who have oral sex with six or more partners triple their risk of developing oral cancer due to the transmission of the papilloma virus, according to a recent study from Johns Hopkins University in Baltimore.

Yet, medical advice on how to prevent cancer usually centers on avoiding tobacco, sunlight, cancer-causing foods, and environmental pollution, with only secondary mention of the need for protection against infections by cancer-causing viruses. “We worry about ‘Should I eat those french fries or that apple?’ but we don’t manage our infections. I don’t say, ‘I think I’ll have a little less Epstein-Barr virus today,’ ” said Dr. Julie Parsonnet, a researcher at Stanford Comprehensive Cancer Center in California who focuses on infectious diseases. “We are probably focusing on the wrong thing.”

Ultimately, Parsonnet believes that infections from viruses and bacteria combined account for at least a quarter of cancers and more in developing countries where untreated infections are more common. However, Parsonnet hopes the advent of the vaccine against cervical cancer, Gardasil, in 2006, may have begun to raise awareness. The maker, Merck & Co., ran national television advertisements that depicted average women expressing their surprise that cancer could be brought on by a viral infection. “That for the first time brought infections to the public mind as a cause of cancer,” Parsonnet said.

Scientists suspected long ago that cancer could be an infectious disease: 19th-century physicians observed that cervical cancer was common among prostitutes and rare among nuns, suggesting the disease was spread through sex. But it wasn’t until the last 50 years that researchers began to draw the direct connection between viruses – organisms that need to get inside healthy cells in order to survive – and the nation’s second leading killer. Even now, researchers are still figuring out exactly how the viruses cause cancer.

The human papilloma virus makes proteins that corrupt cells inside body openings such as the mouth and vagina, causing the cells to live longer and reproduce more frequently. Unchecked, the genetically defective cells can grow and spread, disfiguring and potentially killing its victims. But only one-third of the more than 100 strains of papilloma have been linked to cancer, and even those trigger cancer in a tiny fraction of infected people: More than 20 million women will be infected with papilloma virus this year, for instance, but only about 11,000 will be diagnosed with cervical cancer.

A second group of cancer-causing viruses, hepatitis B and C, attack the liver, where they take over healthy cells and also cause inflammation that further damages the cells. Millions of people carry these viruses with virtually no symptoms, but the 10 percent of patients who suffer chronic liver inflammation have an increased chance of developing cancer, cirrhosis, or liver failure.

Viruses often prey on people already suffering from another disease that has weakened their immune systems, making them more vulnerable. The Kaposi sarcoma associated herpesvirus is best known in this country for striking HIV patients, causing widespread skin lesions and sometimes death when the cancer spreads to the lungs. The Kaposi virus illustrates how viruses can cause cancer without being detected: In addition to taking over some cells to use as “hosts,” the Kaposi virus quietly kills neighboring cells, allowing cancer to spread without any genetic “fingerprint” left behind. Dr. Preet Chaudhary, the University of Pittsburgh medical school researcher who discovered Kaposi’s cell-killing ways, believes that other viruses may do the same thing, but no one has noticed. “It is possible that the actual cancers that are linked to viral infections are much more common than we realized,” said Chaudhary.

Scientists don’t know why different viruses are so selective in causing cancer, but Parsonnet believes the answer lies in the complex relationship between humans and the viruses inside them. The difference between a harmless virus and a deadly infection, she said, may come down to very specific details, or a cascade of unconnected events. “Maybe herpes causes cancer but only if you previously had CMV (cytomegalovirus) and an exposure to hepatitis A before you were three,” she speculated.

Meyerson of Dana-Farber said it may be time for a systematic approach to studying cancer-causing viruses. The Human Genome Project, which identified the 25,000 or so human genes, could help researchers find microbial invaders in human tissue and fluids: If scientists find genes that aren’t in the genome, they must be from a nonhuman source such as viruses or bacteria. “Once we find the first new pathogen with this approach, the field will explode,” Meyerson predicts.

In the meantime, oral cancer survivor Hill and his wife get tested regularly to see if the papilloma virus has returned, and he wants health officials to do more to fight viruses now. Hill’s California-based Oral Cancer Foundation (www.oralcancer.org) is pushing to get the new cervical cancer vaccine, which protects girls against HPV-16 and HPV-18, to be offered to boys as well – something the vaccine makers are investigating. It’s possible, he said, to eradicate one major cancer-causing virus a generation from now. “We must act now.”

This article was authored by Scott Allen of the Boston Globe

Tags: HPV, Oral Cancer News, The Changing Demographics by oc advocate
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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.

Tags: HPV, Oral Cancer News, Salivary Diagnostics, Screening, The Changing Demographics by oc advocate
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