The Oral Cancer Advocate

Researchers found that even devoid of smoke, tobacco remains a carcinogen hazard. Smokeless tobacco exposes users to at least as much of a potent carcinogen as smoking tobacco does, despite claims that it is a safer alternative, reported Stephen S. Hecht, Ph.D., of the University of Minnesota, and colleagues, in the August issue of Cancer Epidemiology, Biomarkers & Prevention.

Smokeless tobacco users had 73% higher levels of a biomarker for a nitrosamine carcinogen known as NNK than did smokers in pooled analysis of six studies (P<0.0001), they found. NNK (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone) is the worst of the strong carcinogens most prevalent in smokeless tobacco, they said. In animals, it has been shown to induce tumors in the lung, pancreas, nasal mucosa, and liver.

Their findings represent “an unacceptable risk” and weigh against oral snuff as a healthier substitute for smoking, they said. “Long-term use of nicotine replacement therapy may be a better option.”

Smokeless tobacco has been considered less toxic and carcinogenic than smoking because it has less of the harmful substances formed by burning the tobacco, they noted. Therefore, some tobacco control experts have suggested that smokers who cannot quit could switch to “low nitrosamine” smokeless tobacco to reduce their health risks, they said.

To see if this claim was true, the researchers used data collected at baseline from three intervention studies of smokers and three of smokeless tobacco users. The 420 smokers (62% men) averaged 25.8 cigarettes per day. The 182 smokeless tobacco users (all men) averaged 4.2 tins per week of predominantly Kodiak (47.0%), Copenhagen (31.5%), or Skoal (12.7%) tobacco.

Gender, age, weight, and race were significantly different between the two groups (P<0.0001). Exposure to the carcinogen NNK was estimated using the urinary biomarker total NNAL, which consists of NNK metabolites 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides.

After controlling for age and gender, smokeless tobacco users had significantly higher median total NNAL per milliliter of urine than did smokers (3.76 versus 2.18 pmol/mL for men median age 45, P<0.0001). Smokeless tobacco users also had 32% higher total NNAL per milligram of creatinine than did smokers (2.83 versus 2.15 pmol/mg creatinine for men median age 45, P<0.001).

Estimated 24-hour excretion of total NNAL was higher among younger male smokeless tobacco users than younger male smokers (4.3 versus 3.5 nmol). The levels of cotinine, a biomarker of nicotine exposure, were significantly higher in smokeless tobacco users than in smokers (42.1 versus 21.7 nmol/mL and 28.1 versus 22.2 nmol/mg creatinine, respectively, both P<0.001). The estimated mean daily cotinine levels in their urine were 49 Amol for smokeless tobacco users compared with 33 Amol for smokers.

Pharmacokinetics from other studies suggest that nicotine intake was likely similar between groups, Dr. Hecht and colleagues said. “These results show that, in a treatment-seeking population, smokeless tobacco users strive to achieve similar nicotine levels as do cigarette smokers in order to satisfy their craving,” they wrote.

Because exposure to NNK was at least comparable in smokeless and smoking tobacco users, the findings “raise serious questions about the strategy of using smokeless tobacco as a substitute for cigarette smoking” with the rationale that smokeless tobacco is safer, the researchers said.

They pointed out that the lung cancer risk is doubtless higher for smokers than smokeless tobacco users, as cigarette smoke contains, in addition to NNK, multiple carcinogenic combustion products which are not present, or present in only low amounts, in smokeless tobacco. Furthermore, NNK is directly deposited in the lungs of smokers, which is likely to increase its carcinogenic effect in that organ. However, “the data presented here show that smokeless tobacco use is far from safe,” they concluded.

This article was written from the original research work by: Crystal Phend, Staff Writer, MedPage Today

Notes:
1. Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.

2. The study was supported by grants from the National Institutes of Health. Two of the researchers reported grant support from the American Cancer Society and National Institute on Drug Abuse, respectively

Tags: Tobacco Harm Reduction 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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