squamous cell carcinoma

Ethanol Promotes Chemically Induced Oral Cancer in Mice through Activation of the 5-Lipoxygenase Pathway of Arachidonic Acid Metabolism

Source: Cancer Prevention Research

Abstract

Alcohol drinking is a known risk factor for oral cancer in humans. However, previous animal studies on the promoting effect of ethanol on oral carcinogenesis were inconclusive. It is necessary to develop an animal model with which the molecular mechanism of ethanol-related oral carcinogenesis may be elucidated to develop effective prevention strategies. In this study, mice were first treated with 4-nitroquinoline-1-oxide (4NQO, 100 μg/mL in drinking water) for 8 weeks and then given water or ethanol (8%) as the sole drink for another 16 weeks. During the experiment, 8% ethanol was well tolerated by mice. The incidence of squamous cell carcinoma (SCC) increased from 20% (8/41) to 43% (17/40; P < 0.05). Expression of 5-lipoxygenase (5-Lox) and cyclooxygenase 2 (Cox-2) was increased in dysplasia and SCC of 4NQO-treated tongues and further enhanced by ethanol. Using this mouse model, we further showed that fewer cancers were induced in Alox5−/− mice, as were cell proliferation, inflammation, and angiogenesis in the tongue, as compared with Alox5+/+ mice. Interestingly, Cox-2 expression was induced by ethanol in knockout mice, whereas 5-Lox and leukotriene A4 hydrolase (LTA4H) expression and leukotriene B4 (LTB4) biosynthesis were dramatically reduced. Moreover, ethanol enhanced expression and nuclear localization of 5-Lox and stimulated LTB4 biosynthesis in human tongue SCC cells (SCC-15 and SCC-4) in vitro. In conclusion, this study clearly showed that ethanol promoted 4NQO-induced oral carcinogenesis, at least in part, through further activation of the 5-Lox pathway of arachidonic acid metabolism.

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

October, 2011|Oral Cancer News|

Resveratrol Selectively Induces DNA Damage, Independent of Smad4 Expression, in Its Efficacy against Human Head & Neck Squamous Cell Carcinoma

Source: Clinical Cancer Research
Author: Robert A. Sclafani, University of Colorado School of Medicine, Campus Box 8101, Room 9100, Aurora, CO 80045. Phone: 303-724-3271; Fax: 303-724-3215; E-mail:Robert.Sclafani@ucdenver.edu

 

Abstract

Purpose: Alterations in Smad4 signaling and its loss cause genomic instability and head and neck squamous cell carcinoma (HNSCC), suggesting that agents that target both Smad4-dependent and -independent pathways could control HNSCC.

Experimental Design: Resveratrol efficacy was evaluated against the HNSCC cells FaDu, Cal27, Det562, and Cal27-Smad4 for viability, DNA damage, cell-cycle progression, and apoptosis, as well as γ-H2AX expression, and focus formation (γ-H2AX and Brca1). Resveratrol efficacy was also examined in nude mice for FaDu xenograft growth. Xenografts were analyzed for γ-H2AX and cleaved caspase-3.

Results: Resveratrol (5–50 μmol/L) suppressed viability and induced DNA damage in FaDu and Cal27 cells but not in normal human epidermal keratinocytes and human foreskin fibroblasts, showing its selectivity toward HNSCC cells; however, Det562 cells were resistant to resveratrol even at 100 μmol/L. Cal27 cells stably transfected withSmad4 showed similar resveratrol effects as parental Cal27, indicating that a lack of resveratrol effect in Det562 cells was independent of Smad4 status in these cells. Furthermore, resveratrol caused S-phase arrest and apoptotic death of FaDu and Cal27 cells together with induction of Brca1 and γ-H2AX foci. Resveratrol (50 mg/kg body weight) treatment also inhibited FaDu tumor growth in nude mice, and γ-H2AX and cleaved caspase-3 were strongly increased in xenografts from resveratrol-treated mice compared with controls.

Conclusion: Our findings for the first time showed antiproliferative, DNA damaging, and apoptotic effects of resveratrol in HNSCC cells independent of Smad4 status, both in vitro and in vivo, suggesting that more studies are needed to establish its potential usefulness against HNSCC. Clin Cancer Res; 17(16); 5402–11. ©2011 AACR.

This article is featured in Highlights of This Issue, p. 5215

  • Received April 21, 2011.
  • Revision received June 10, 2011.
  • Accepted June 16, 2011.
August, 2011|Oral Cancer News|

New Study on Tonsillar Squamous Cell Carcinoma

Source: SAGE Journals Online

Objective. To analyze outcomes in patients with squamous cell carcinoma (SCCA) of the tonsil from the years 1998 to 2006. To assess factors that may affect disease-specific survival, such as patient characteristics and/or treatment modality.

Study Design and Setting. National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) program.

Subjects and Methods. The SEER database was used to perform a population-based cohort analysis for patients diagnosed with SCCA of the tonsil from 1998 to 2006. Disease-specific survival was correlated with sex, age, ethnicity, year of diagnosis, and treatment modality in a univariate Cox proportional hazards analysis and a multiple Cox-regression model with and without interaction effect.

Results. Applied inclusion criteria resulted in 8378 patients. Of this patient cohort, 80% were male and 85% were white. The mean patient age at diagnosis was 58.1 years. On univariate and multivariate analyses, ethnicities other than white carried a significantly higher rate of disease-specific death (hazard ratio = 1.71, P < .001). Each additional year of age at the time of diagnosis carried approximately a 4% increase in likelihood of disease-specific death. With each passing year of time at diagnosis, patients carried a decreased risk of disease-specific death (P < .001); this value was significant in all 3 statistical models. Patients who underwent external-beam radiation had a higher likelihood of disease-specific survival with each passing year at time of diagnosis. Conclusion. Population analysis based on the SEER database reveals increased disease-specific survival from tonsillar SCCA in more recent years. This may be because of earlier diagnosis, an increase in less aggressive subtypes of SCCA, and more effective treatment modalities. This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

August, 2011|Oral Cancer News|

New Strategies used to Identify Changes in Head and Neck Cancers

Source: GenomeWeb Daily News
By Andrea Anderson

CHICAGO– Researchers are making progress using high-throughput strategies to find previously unappreciated genetic and epigenetic quirks in head and neck cancer — including changes that may prove useful for diagnosing and tracking disease.

Johns Hopkins University head and neck cancer research director David Sidransky described some of the work during an education session on molecular biology, targets, and pathways involved in head and neck cancer at the American Society of Clinical Oncology annual meeting here yesterday.

Speaking during the same session, JHU oncologist Christine Chung and the University of Chicago’s Ezra Cohen touched on strategies for targeting the types of mutations previously reported in head and neck cancer and the rationale behind targeted therapeutics already being tested or considered for the disease, respectively.

Past studies have uncovered muted DNA methylation across the genomes of several cancer types, Sidransky explained, though methylation is also bumped up at specific sites in certain tumor types.

Consequently, he said, researchers are using strategies such as real-time quantitative methylation-specific PCR (real-time QMSP) to look at methylation shifts in head and neck squamous cell carcinoma.

In particular, he described work comparing methylation patterns in saliva and serum samples from individuals with HNSCC to those in samples from more than 800 apparently healthy individuals who are considered ‘at-risk’ of the disease because of smoking status and other exposures.

At least two genes — KIF1A and EDNRB — seem to be more highly methylated in samples from those with HNSCC than at-risk control individuals, Sidransky said, suggesting methylation of these genes might prove useful for diagnosing and monitoring the disease.
Researchers are also finding mutations and rearrangements in several genes that appear to be promising biomarker candidates for distinguishing between HNSCC cases and controls using DNA from blood samples.

Moreover, Sidransky outlined some preliminary findings from exome sequencing studies of 32 head and neck cancer samples, followed by validation in another 88 samples.

Consistent with previous findings for HNSCC, he and his collaborators have found mutations in TP53 in nearly half of the tumors tested, Sidransky said.

But they are also seeing mutations in several other genes not previously linked to the disease, including NOTCH1 — a gene that’s known to be mutated in leukemia and other types of cancer. While NOTCH1 mutations are often activating in other cancers, he noted, results so far hint that the gene is frequently inactivated in HNSCC.

In addition, findings from the exome sequencing study point to genetic and epigenetic differences in HNSCC tumors that correspond to the human papilloma virus status. For example, Sidransky said, HPV positive tumors each tend to have fewer mutations overall compared to HPV negative tumors, which often come from smokers.

At the American Association for Cancer Research annual meeting in Orlando earlier this year, researchers from the Broad Institute and the University of Pittsburgh reported on findings from their own genome and exome sequencing studies of head and neck cancer, including whole exome data for 28 tumor-normal pairs and whole genome data for two tumor-normal pairs.

That team identified frequent mutations in TP53, HRAS, PIK3CA, and PTEN, along with somatic rearrangements and recurrent mutations in additional oncogenic pathways.

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

Two Elements Predict Swallowing Difficulties after Radiotherapy

Source: International Medicine News

LONDON – Nonglottic cancer and the presence of dysphagia before treatment are highly predictive for severe acute and late swallowing difficulties after radiotherapy for head and neck cancer, according to new data from the DAHANCA 6&7 randomized trial.

Patients with nonglottic cancer were more likely than those with other cancer types to experience severe dysphagia at both 6 and 12 months. Dysphagia before treatment was also associated with both acute and late severe swallowing difficulties.

“The peak incidence of dysphagia is seen during the first 6 months after radiotherapy,” Hanna Rahbek Mortensen, Ph.D., reported in an analysis of the DAHANCA (Danish Head and Neck Cancer Group) 6&7 trial findings at the European Society for Therapeutic Radiation Oncology Anniversary Congress.

“After 1 year, however, there is no further increase in severity or prevalence,” said Dr. Mortensen of the department of experimental clinical oncology at Åarhus (Denmark) University Hospital.

The trial involved 1,478 patients with squamous cell carcinomas of the glottic larynx, supraglottic larynx, pharynx, or oral cavity who were who were treated with five or six weekly fractions of radiotherapy in 1992-1999. The total dose of radiotherapy delivered was 66-68 Gy in 33-34 fractions.

Efficacy data from the trial have already been published; they showed improved disease-specific but not overall survival of five vs. six fractions of radiotherapy (Lancet 2003;362:933-40).

The aim of the present analysis was to use prospectively collected data from the trial to determine whether any factors could be used to establish which patients may be more likely than others to experience dysphagia following treatment.

“Dysphagia is a common and debilitating side effect of radiotherapy, leading to malnutrition, aspiration, and reduced quality of life,” Dr. Mortensen explained. The side effect can be graded using a 5-point scale, with a score of 0 signifying no dysphagia and a score of 3 or 4 indicating considerable or severe dysphagia despite the ingestion of a liquid-only diet.

In all, 1,422 (96%) patients experienced acute dysphagia, including severe grade 3/4 dysphagia in 47% and 38% of those receiving accelerated or conventional radiotherapy, respectively. The two factors most predictive for severe dysphagia at 6 months were nonglottic cancer (odds ratio, 6.73 vs. other sites; P less than .0001) and a baseline dysphagia score of 2-4 vs. 0-1 (OR, 2.11; P =.004).

Odd ratios for other factors predictive for acute – but not late – dysphagia were 1.92 for any (N1-N3) vs. no (N0) nodal involvement (P less than .001), 1.82 for the use of accelerated (six weekly fractions) vs. conventional (five weekly fractions) radiotherapy (P less than .001), and 1.58 for stage T3-T4 vs. stage T1-T2 cancer (P = .02).

After 5-years of regular follow-up, late dysphagia had occurred in 1,205 patients (81%), with grade 3 severity in 24% and grade 4 in 23%. Factors that were predictive for late severe dysphagia that occurred 12 months after radiotherapy were, again, nonglottic cancer (OR, 8.25; P less than .0001) and a baseline dysphagia score greater than 1 (OR, 2.57; P less than .002). Late (T3-T4) tumor stage was also predictive (OR, 1.86; P = .03).

“Predictive factors have been identified to characterize patients at risk of developing acute and late dysphagia,” Dr. Mortensen said. These factors may be useful to identify patients who could perhaps benefit from prophylactic measures against swallowing dysfunction.

The DAHANCA 6&7 trial was supported by the Danish Cancer Society, Åarhus University Hospital, Copenhagen University Hospital, Herlev (Denmark) Hospital, Odense (Denmark) University Hospital, and Aalborg (Denmark) Hospital on behalf of DAHANCA. Dr. Mortensen had no personal financial disclosures to declare.

 

Oral Cancer…what does sex have to do with it?

Source: DentistryIQ.com

The answer is … plenty! This issue will focus on oral cancer awareness. While there are many topics we can delve into regarding this dreadful disease, we will focus on a few topics.

We will share two personal and very poignant stories. Kim Anzalotti, Bill Wislon, and Eva Grayzel impart information that will move you and make you think about your daily in-office procedures. JoAnn Gurenlian, RDH, PhD, will share insights on the human papillomavirus, or HPV, a sexually transmitted virus, and its relationship to oral cancer. And last, but certainly not least, Jamie O’Day, Treatment Facilities Coordinator, The Oral Cancer Foundation Inc., The Bruce Paltrow Oral Cancer Fund, will share her insight on oral cancer screening and the need for a thorough examination.

One personal story is shared by Eva Grazel, an international motivational speaker, author, performer, and cancer survivor. I had the pleasure of meeting Eva a number of years ago. In 1998 at age 33, Eva, a non-smoker, saw a number of dentists and physicians for over two years for an “ulcer” on her tongue that became larger and more painful, without any resolution. She was finally diagnosed with advanced oral cancer, Stage IV squamous cell carcinoma, on the lateral border of her tongue.

After the many missed opportunities for diagnosis, Eva was given a 15% chance of survival. While her late stage diagnosis is not uncommon, her recovery was unique, as she beat the odds. After diagnosis, Eva underwent a partial tongue reconstruction, a modified radical neck dissection, and a maximum dose of radiation therapy. The good news is that Eva is very much alive today, and helps to motivate professionals and patients about oral cancer examinations and risk factors. She also authored the Talk4Hope book series, written to inspire children and parents who have a family member with cancer.This Family Book Series helps families cope with their feelings about cancer, enlightens parents on how to communicate with their children, and creates special moments to cherish. Read Eva’s contribution in this eVillage FOCUS issue.

For the 12th year in a row, April was the official oral cancer awareness month in the U.S. Oral cancer awareness means raising public awareness through group collaboration to ensure that oral cancers get the national media attention necessary to highlight risk factors and oral cancer screening. Free oral cancer screenings were held throughout the country. But it does not have to be a special month to conduct oral cancer screenings in the community. There are a variety of forms for editable press releases for events. Conduct your community activity when it is convenient for you.

Rates of oral cancer are on the rise among men, and researchers say the cause is not the use of tobacco and alcohol, risk factors we have been aware of for years. The number of smokers in the U.S. has steadily declined in the past 50 years, according to the CDC, yet the rate of oral cancer has remained relatively steady, and has recently been on the increase. The culprit is the human papillomavirus, or HPV, the sexually transmitted virus responsible for the majority of cases of cervical cancer in women. Approximately 65 percent of oral cancer tumors were linked to HPV in 2007, according to the National Cancer Institute.

The profile of these new cases of oral cancer is non-smokers who are predominantly white, upper middle class, college-educated men. HPV-16, the strain of the virus that causes cervical cancer in women, has become the leading cause of oral cancer in non-smoking men. Oral HPV infection was strongly associated with oropharyngeal cancer among subjects with or without the established risk factors of tobacco and alcohol use in this case-controlled study. An even greater than-additive risk has been reported, although inconsistently, for patients exposed to both HPV and tobacco and those exposed to both HPV and alcohol.

A University of North Carolina (UNC) study found the incidence of oral tongue cancer increasing in young, white females, even though overall, incidence of oral cavity squamous cell carcinoma (OCSCC) was decreasing for all ages. The increasing incidence was most dramatic for white females ages 18 to 44. They had a percentage change of 111 percent.

Interestingly, the incidence decreased for African American and other racial groups. They analyzed incidence and survival data from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute from 1975 to 2007 for OCSCC and oral tongue squamous cell carcinoma (OTSCC).

 

There is an enormous effort to vaccinate girls and women between the ages of 11 and 26 against HPV, and according to experts, should have included boys and men from the beginning. Gardasil (Merck), one of the two major vaccines used to prevent HPV infection, wasn’t approved for use in males in the United States until 2009, three years after it was approved for women. Men have a greater chance of contracting the HPV virus from oral sex than women do from the same behavior, though researchers are not clear on the reason for this phenomenon. For CDC information on HPV vaccines, visit their website.

 

The other vaccine is Cervarix (GlaxoSmithKline). According to the CDC, both vaccines are very safe, and are made with very small parts of the human papillomavirus (HPV) that cannot cause infection. As with any pharmaceuticals, there can be side effects. For a recently updated Q & A page on these vaccines, visit the CDC website.

In girls and young women ages 9 to 26, Gardasil® helps protect against two types of HPV that cause about 75% of cervical cancer cases, and two more types that cause 90% of genital warts cases. In boys and young men ages 9 to 26, Gardasil helps protect against 90% of genital warts cases. Gardasil also helps protect girls and young women ages 9 to 26 against 70% of vaginal cancer cases and up to 50% of vulvar cancer cases.

While the vaccines available are not approved for prevention of oral cancer, the impact the vaccines may have on oral cancer should be considered. The Oral Cancer Foundation believes that elimination of a causative agent (HPV16), by preventing infection from it by use of a vaccine, will subsequently prevent any disease that agent may have produced in the protected individual. This is simple scientific extrapolation, and a view shared by many in the science community. Makes sense to me!

Oral cancer has a low survival rate because it is generally not discovered until it has spread to other areas, according to the CDC. Only half of people who’ve been diagnosed with oral cancer will live longer than five years. Prevention is the name of the game. Do not use tobacco products, use alcohol in moderation, limit the number of sexual partners and use protection, and screen (or be screened) annually for oral cancer. Anyone old enough to have engaged in sexual behaviors which are capable of transferring the HPV needs to be screened annually for oral cancer. There are many cancer screening protocols available. Education, prevention, screening and early intervention can save lives.

 

HPV is now the leading cause of oral cancer in the US: learn the facts.

Source: New York Daily News

HPV, otherwise known as the human papillomavirus, is a leading cause of cervical cancer for women but the nasty virus is now causing a spike in oral cancer and ravaging an entirely different group: men.
Cases of oral cancer resulting from exposure to the HPV-16 strain of the virus are hitting epidemic proportions in the U.S., doctors say.

Though the mention of oral cancer evokes images of gravely-voiced chain-smokers, the disease now has a new face: mostly white, male, non-smokers in their late 30s and early 40s.

The tumors forming on the back of their tongues and tonsils have nothing to do with nicotine – they are directly linked to engaging in oral sex with multiple female partners.

“If you’ve had more than five or six sexual partners, you are at a higher risk,” Dr. Eric M. Genden, professor and chair of head and neck surgery at Mount Sinai Medical center told the Daily News. “We’re only now beginning to see the beginning of a bell curve.”

Women can get it from men as well although their chances are lower, according to doctors.

The human papillomavirus (HPV), a nasty bug with strains that causes genital warts and cervical cancer in women, is now the top cause of oral cancer in men, beating out smoking and drinking, according to reports from the New England Journal of Medicine and the Journal of Oncology as well as other research and treating institutions.

The number of smokers in the U.S. has steadily declined in the past 50 years, yet the rate of oral cancer has remained relatively steady, and recently been on the increase.

The reason is an increase in HPV-16 in the U.S. population.

Oral cancer is frightening because it often goes undetected until a lump appears on the neck or a patient begins to suffer from a persistent hoarseness. By then, even though the patient may feel fine, he could be in the late stages of the deadly disease.

If detected early, the chance for surviving oral cancer from HPV is high, between 85 to 90%. Treatments – localized radiation, chemotherapy, and sometimes surgery – are effective when used in the early stages. When surgery is part of the solution, the options can be conventional surgery or a new robotic surgical technique, which reduces scarring and side effects in some patients.

Brian Hill, a medical device manufacturer, was in his mid-forties when found a hard spot on his neck 14 years ago. He went to his ear, nose and throat doctor, who dismissed the bump as an infection and prescribed antibiotics.

But a biopsy later found the lump was cancerous.

Though he had never smoked a cigarette, Hill was told he had a low chance of survival as the node in his neck was positive for squamous cell carcinoma, the most common oral cancer.

Hill has since founded the Oral Cancer Foundation and spends his time working with patients, doctors and dentists, as well as campaigning in Washington to raise awareness about the danger of oral cancer and the links to HPV.

“Anyone old enough to have engaged in sexual behaviors known to transmit this virus needs to be screened annually for oral cancer,” said Hill. “It’s the only way to catch this disease at its early stages.”

Hill believes many doctors and researchers are still in the dark about the ties between HPV-16 and oral cancer, despite the rise in diagnoses in the past decade.

“We don’t know exactly if or how long HPV-16 may lay dormant, or why it strikes certain people and not others,” he said. “What we don’t know exceeds what we do know.”

Nearly all sexually active Americans will come in contact with HPV, according to the Oral Cancer Foundation and the National Institutes of Health.

Young women are encouraged to get the HPV vaccine, but doctors say there is little point in vaccinating patients past the age of 26 since the likelihood of prior exposure to cancer-causing strains is so high.

Young people now are having a lot more oral sex with many more partners so exposure rates are higher.

HPV is the most common STD in the U.S. About 20 million Americans are currently infected with HPV. Another 6 million people become newly infected each year, according to the Centers for Disease Control and Prevention.

HPV is passed through skin-to-skin contact, not fluids. Besides conventional sex, oral sex and even deep French kissing may spread the virus.

Doctors are sounding the alarm, but have stopped short of advising men to abstain.

“This is not a call to stop having oral sex,” said Dr. Mark D. DeLacure, a head and neck surgeon at NYU’s Langone Medical Center. “People have to continue living their lives, however we make the best choices when we know all the risks.”

DeLacure said using condoms and dental dams during oral sex could reduce transmission, but acknowledges the idea is hardly appealing or practical.

“Limiting your sexual partners is a way to reduce your risk,” said DeLacure. “But still, there are no guarantees.”

Doctors also have this advice: Don’t panic.

Patients with HPV – even the cancer-causing strain – may never develop cancer and may never transmit the virus to a partner.

The vast majority of individuals have immune systems that recognize the virus as a threat, and easily defeat it.
Doctors instead recommend vigilance.

The important issue is persistence – meaning attention to how long an unusual symptom like a lump has lasted. When an abnormality persists for longer than 14 to 21 days, it’s time to see an expert.

“If you’ve got a sore tonsil that is still a problem after a couple of weeks, and particularly if it’s localized to one side, I would say that’s sign it’s time to talk to a doctor,” said DeLacure.

And talk to the person who sees your mouth the most: Your dentist.

Dentists, too, are becoming more aware of HPV and its role in the development of oral cancer.

A good dentist will know what to look for and where to look for it.

Tonsillar squamous cell carcinoma- are we making a difference?

Source: SAGE Journals Online

Objective. To analyze outcomes in patients with squamous cell carcinoma (SCCA) of the tonsil from the years 1998 to 2006. To assess factors that may affect disease-specific survival, such as patient characteristics and/or treatment modality.

Study Design and Setting. National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) program.

Subjects and Methods. The SEER database was used to perform a population-based cohort analysis for patients diagnosed with SCCA of the tonsil from 1998 to 2006. Disease-specific survival was correlated with sex, age, ethnicity, year of diagnosis, and treatment modality in a univariate Cox proportional hazards analysis and a multiple Cox-regression model with and without interaction effect.

Results. Applied inclusion criteria resulted in 8378 patients. Of this patient cohort, 80% were male and 85% were white. The mean patient age at diagnosis was 58.1 years. On univariate and multivariate analyses, ethnicities other than white carried a significantly higher rate of disease-specific death (hazard ratio = 1.71, P < .001). Each additional year of age at the time of diagnosis carried approximately a 4% increase in likelihood of disease-specific death. With each passing year of time at diagnosis, patients carried a decreased risk of disease-specific death (P < .001); this value was significant in all 3 statistical models. Patients who underwent external-beam radiation had a higher likelihood of disease-specific survival with each passing year at time of diagnosis.

Conclusion. Population analysis based on the SEER database reveals increased disease-specific survival from tonsillar SCCA in more recent years. This may be because of earlier diagnosis, an increase in less aggressive subtypes of SCCA, and more effective treatment modalities.

March, 2011|Oral Cancer News|

Expand the search for oral cancer

Dentistry’s responsibilities remain vital in stopping cancer deaths

By: Donna Grzegorek, RDH

Source: RDH magazine

As dental professionals, we have a remarkable opportunity to affect the health and well-being of each patient we treat. This responsibility manifests itself in patients’ expectations, which is to inform them of disease at the earliest possible moment. This is the fifth consecutive year in which there has been an increase in the rate of occurrence of oral cancers; yet, for several decades the mortality rates for this insidious disease remained virtually unchanged. OCF As dental professionals and health-care providers, we have an obligation to be vigilant in our commitment to early detection, raising awareness, and the management of the cancer for which we as a profession are held accountable.

Approximately 37,000 Americans will be diagnosed with oral or pharyngeal cancer this year. This menacing disease will cause 8,000 deaths, killing approximately one person per hour, 24 hours a day. Of these 37,000 newly-diagnosed individuals, only slightly more than half will survive five years. The mortality rate for oral cancer is higher than that of other cancers we hear about routinely such as cervical cancer, Hodgkin’s lymphoma, laryngeal cancer, cancer of the testes, and endocrine system cancers such as thyroid or skin cancer (malignant melanoma). If you expand the definition of oral cancers to include cancer of the larynx, for which the risk factors are indistinguishable, the number of diagnosed cases grows to approximately 50,000 individuals and 13,500 deaths per year in the United States alone. Worldwide, the problem is much greater, with 640,000 new cases being diagnosed each year.

The brutal reality

The death rate associated with oral cancer is particularly high, not because it is hard to discover or diagnose, but because the cancer is routinely discovered late in its development. Often, it is only discovered when the cancer has metastasized to another location, most likely the lymph nodes of the neck. Prognosis at this stage of discovery is appreciably worse than when it is caught early in a localized intraoral area. In addition to the metastasis at these later stages, the primary tumor has had time to invade deep into local structures.

Oral cancer is particularly perilous because in its early stages it may not be noticed by the patient, as it can frequently prosper without producing pain or symptoms they might readily recognize, and because it has a high risk of producing secondary tumors. Patients who survive a first encounter with the disease have up to a 20 times higher risk of developing a second cancer. This heightened risk factor can last for five to 10 years after the first occurrence. There are several types of oral cancers, but approximately 90% are squamous cell carcinomas. According to the Oral Cancer Foundation, it is estimated that approximately $3.2 billion is spent in the United States each year on treatment of head and neck cancers.

Human papilloma virus connection

One of the most common virus groups in the world today affecting the skin and mucosal areas of the body is the human papilloma virus. Over 120 different types/versions of HPV have been identified. Most HPVs of this type are very common, harmless, noncancerous, and easily treatable. There are other forms of HPV, which are sexually transmitted, and some of these are a serious problem. The most common of these are HPV-16, HPV-18, HPV-31, and HPV- 45.

Two types of genital tract HPV in particular, HPV-16 and HPV-18 are known to cause the vast majority of cervical cancers, and recent studies show one of them, HPV-16, to be linked to oral cancer as well. In the oral cavity, HPV-16 manifests itself primarily in the posterior regions such as the base of the tongue, the oropharynx, the tonsils and the tonsillar pillars. These oncogenic versions of HPV are also responsible for other squamous cell carcinomas, particularly the anus and penis.

It has now been established that the pathway that brings people to oral cancer contains at least two distinct etiologies: one through tobacco and alcohol and the other via the HPV virus, particularly HPV-16. In the broadest terms, they can be differentiated into HPV-related cancers and non-HPV positive tumors.

Researchers now feel that HPV positive tumors occur most frequently in a younger group of individuals than tobacco-related malignancies. Tobacco oral cancers occur most frequently in the fifth through seventh decade of life. The HPV positive group is the fastest growing segment of the oral cancer population.

Oral Cancer Foundation takes a strong stand

The Oral Cancer Foundation has taken the following position regarding the HPV connection: “We strongly believe that in a younger population of nonsmoking oral cancer patients, HPV is presenting itself as the dominant causative factor. Since the historic definition of those who need to be screened is now changed by this newly defined HPV etiology, and is no longer valid, it is not possible to definitively know who is at risk for the development of the disease, and who is not.

“Simply stated, today anyone old enough to have engaged in sexual behaviors which are capable of transferring this very ubiquitous virus needs to be screened annually for oral cancer. For this reason we are strong promoters of opportunistic annual screenings to catch this disease at its earliest possible stages, when it is most vulnerable to existing treatment modalities and survival rates are the highest.

“We believe that this will bring the oral cancer death rate down as early detection and diagnosis takes place, and will reduce the treatment associated morbidity to patients who do present with oral cancers.”

Dentistry’s responsibility

Published studies show that currently less than 15% of those who visit a dentist regularly report having had an oral cancer screening. This is unfortunate when you consider that, historically, the greatest strides in combating most cancers have come from increased awareness and aggressive campaigns directed at early detection.

It is commonplace to annually seek a PAP smear for cervical cancer, a mammogram to check for breast cancer, or PSA and digital rectal exams for prostate cancer. These screening efforts have been successful as a result of increased public awareness of the value of catching cancers in their earliest forms, combined with effective technologies for conducting the examinations.

Oral cancer is no different. It may be potentially easier to obtain public compliance for oral cancer screenings, since unlike many other cancer screening procedures, there is no invasive technique necessary to look for it, no discomfort or pain involved, and it is very inexpensive to have one’s mouth examined for the early signs of disease. Creating awareness, discovery, diagnosis, and referral are the primary responsibilities of the dental community.

It is important for both patients and dental professionals to recognize that a visit to the dental office is no longer about a filling, a crown, or a cleaning but is actually a matter of life and death.

Dental examinations that include a comprehensive screening for oral cancer save lives! The most important step in reducing the death rate from oral cancer is early discovery. No other professional is better positioned for early detection or will be held more accountable than members of the dental community.

Foundation supported by dental hygienists

For the past three years, dental hygienists have supported the Oral Cancer Foundation through fund-raising efforts at the RDH Under One Roof conference. The Oral Cancer Foundation is a national public service, nonprofit entity designed to reduce suffering and save lives through prevention, education, research, advocacy, and patient support activities.

Founded by a Stage IV oral cancer survivor, Brian Hill, the foundation’s goals are supported by a scientific advisory board composed of leading cancer authorities from varied medical and dental specialties, drawn from premier cancer treatment, research, and educational institutions in the United States.

The foundation is primarily supported by, and dependent on, donations that are received from private individuals who mostly come from the ranks of survivors, as well as family and friends of those who have had this cancer. The foundation is an IRS registered nonprofit 501(c)3, public service charity designed for advocacy and service, created to promote change through proactive means in both the public and medical/dental professional sectors.

At the forefront of its agenda is the firm establishment in the minds of the American public for the need to undergo an annual oral cancer screening, combined with an outreach to the dental and medical communities to provide this service as a matter of routine practice.

The Oral Cancer Foundation site provides hundreds of pages of information discussing the rates of occurrence, risk factors that lead to oral cancer, signs and symptoms, treatments, current research, complications of treatment, nutrition, related clinical trials, and current oral cancer related news. There is an additional resource page dedicated to links to other sources of vetted information about oral cancer and treatment institutions. The site (www.oralcancerfoundation.org) is updated weekly and provides a plethora of valuable information for the dental professional.

Hill, the founder and executive director, is an excellent resource and is accessible to dental professionals who seek further information regarding his experiences and/or wish to discuss the topic of oral cancer in greater detail (bhill@oralcancerfoundation.org). Hill encourages dental professionals to become members of the foundation and partners with the foundation in their effort to increase the number of annual screenings that are being performed.

Hill states, “Please check the ‘members only’ segment of our Web site, which discusses oral cancer from a practice management perspective, and where you can obtain resources to assist you with the incorporation of a comprehensive cancer screening program to your practice. The dental community is the first line of defense against oral cancer, through the process of early discovery.”

“By regularly screening for oral cancer,” Hill added, “these practices engrain into the public’s mind that a visit to the dentist is about not just cleanings, cosmetics, and crowns, but potentially saving a life. These truly heroic efforts reflect the highest standards of dentistry and a commitment to providing the optimum in not only dental care, but overall health care to patients. Reducing the death rate from oral cancer is tangible, and doable in the immediate future.”

Donna Grzegorek, RDH, has been practicing full-time clinical dental hygiene for 31 years. She is the recipient of several industry recognitions including Discus Dental’s “Hygienist of the Year,” Sunstar America’s “Award of Distinction,” and ADHA’s “Hygienist Hero.” Donna is a published author, speaker, and key opinion leader. She sits on the advisory committee for a salivary diagnostics company, a board member of the American Academy of Dental Hygiene, a member of the International Federation of Dental Hygienists, and a 31-year member of ADHA. She may be contacted at: dgrzegorek@comcast.net.

Second primary cancers after an index head & neck cancer: subsite-specific trends in the era of hpv–associated oropharyngeal cancer

Source: American Society of Clinical Oncology
Authors: Luc G.T. Morris, Andrew G. Sikora, Snehal G. Patel, Richard B. Hayes and Ian Ganly

Abstract

Purpose Patients with head and neck squamous cell carcinoma (HNSCC) are at elevated risk of second primary malignancies (SPM), most commonly of the head and neck (HN), lung, and esophagus. Our objectives were to identify HNSCC subsite-specific differences in SPM risk and distribution and to describe trends in risk over 3 decades, before and during the era of human papillomavirus (HPV) –associated oropharyngeal SCC.

Methods Population-based cohort study of 75,087 patients with HNSCC in the Surveillance, Epidemiology, and End Results (SEER) program. SPM risk was quantified by using standardized incidence ratios (SIRs), excess absolute risk (EAR) per 10,000 person-years at risk (PYR), and number needed to observe. Trends in SPM risk were analyzed by using joinpoint log-linear regression.

Results In patients with HNSCC, the SIR of second primary solid tumor was 2.2 (95% CI, 2.1 to 2.2), and the EAR was 167.7 cancers per 10,000 PYR. The risk of SPM was highest for hypopharyngeal SCC (SIR, 3.5; EAR, 307.1 per 10,000 PYR) and lowest for laryngeal SCC (SIR, 1.9; EAR, 147.8 per 10,000 PYR). The most common SPM site for patients with oral cavity and oropharynx SCC was HN; for patients with laryngeal and hypopharyngeal cancer, it was the lung. Since 1991, SPM risk has decreased significantly among patients with oropharyngeal SCC (annual percentage change in EAR, −4.6%; P = .03).

Conclusion In patients with HNSCC, the risk and distribution of SPM differ significantly according to subsite of the index cancer. Before the 1990s, hypopharynx and oropharynx cancers carried the highest excess risk of SPM. Since then, during the HPV era, SPM risk associated with oropharyngeal SCC has declined to the lowest risk level of any subsite.

January, 2011|Oral Cancer News|