Photodynamic therapy shows promise in head/neck cancer

Author: staff

Photodynamic therapy (PDT) has been shown to be effective as a curative therapy for early cancers of the head and neck, according to research presented at the recent International Photodynamic Association World Congress in Innsbruck, Austria.

Researchers from Ondine Biomedical presented two studies at the conference. In the first, 469 patients with various neoplastic diseases of the head and neck were treated with PDT with follow-up time of up to 250 months. Patients with primary or recurrent carcinoma in situ and T1 carcinomas responded after one PDT treatment, and 88% remained free of the disease, according to the researchers.

The second study focused on the use of PDT to down regulate MMP-9 gene expression in cell cultures of precancerous leukoplakia and oral squamous cell carcinoma. MMP-9 is expressed by squamous cell carcinomas of the head and neck, and is one of the factors responsible for the ability of these cancers to invade into tissue and also to spread to other tissues.

After one treatment of methylene blue PDT, gene expression of MMP-9 was significantly decreased in both the precancerous leukoplakia cells and the oral squamous cell carcinoma cells. This work demonstrated that methylene blue mediated PDT can downregulate proteins that promote the spreading of head and neck carcinoma, therefore potentially reducing the ability of these cancers to invade tissue and spread, the researchers noted.

“These abstracts clearly confirm a role of PDT in the treatment of head and neck cancer,” stated Carolyn Cross, chairman and CEO of Ondine, in a press release.

Pioglitazone Shows Promise for Oral Cancer Prevention

Laird Harrison

Medsscape staff writer

Pioglitazone (Actos, Takeda Pharmaceuticals) “works pretty well — better than anything we’ve seen before,” principal investigator Nelson Rhodus, DMD, MPH, professor of otolaryngology at the University of Minnesota, Minneapolis, toldMedscape Medical News.

Leukoplakia lesions, which are usually caused by irritation, appear on the tongue or sometimes on the insides of the cheek. About 17% of the lesions become invasive cancer, and no treatment has been shown to reliably prevent this, said Dr. Rhodus.

They researchers got interested in pioglitazone because it preserves cell differentiation, enhances apoptosis of tumor cells, and prevents tumor angiogenesis.

In a previous study, the researchers noticed a decrease in head, neck, and lung neoplasms in a population of diabetic men older than 40 years who took thiazolidinedione agents.

For this study, Dr. Rhodus and colleagues from the University of Minnesota, Minneapolis, and the National Cancer Institute in Bethesda, Maryland, recruited 44 patients with lesions characterized histopathologically as either moderate or severe epithelial dysplasia.

The researchers randomly divided these patients so that 22 patients received pioglitazone 45 mg daily for 12 weeks and 22 patients served as a comparison group. Dr. Rhodus’s team measured the leukoplakia lesions and took biopsies of the involved mucosa to evaluate histologic response in all participants.

They determined that 15 of the 22 patients in the pioglitazone group had a clinical and/or histologic response; they did not detect any change in the comparison group.

In the pioglitazone group, the lesions completely disappeared in 3 patients and partially disappeared in 12 patients, the epithelium completely returned to normal in 1 patient, and the dysplasia or hyperplasia reverted from advanced to early, or from early to normal, in 6 patients.

The only adverse reaction was edema, Dr. Rhodus said, and that affected 11% of the pioglitazone group.

“This is a novel finding that is distinctly better than the use of retinoids tried some time ago, which declined because of side effects,” Stephen J. Challacombe, BDS, PhD, a clinical professor of oral medicine and immunology at King’s College London, United Kingdom, told Medscape Medical News.

Because it is a diabetes drug, researchers checked the subjects’ glucose levels, but they found no change, apparently because pioglitazone only affects glucose in diabetics, said Dr. Rhodus.

He cautioned that the results of this phase 2 trial are only preliminary; it is too small to be definitive, and there was no placebo used.

The results merit a larger clinical trial, said John S. Greenspan, BDS, PhD, from the University of California, San Francisco. “I thought it was a fascinating study, an excellent pilot/initial exploration of the safety and efficacy of pioglitazone in the management of oral leukoplakia. If confirmed in larger-scale multicenter trials, this could add an important approach to the control of that lesion.”

In fact, the researchers are now undertaking a phase 3 clinical trial, Dr. Rhodus reported.

If the drug is eventually approved for leukoplakia, it is unlikely that general dentists will prescribe it, he added, but they can identify the types of lesions they should refer to oral surgeons, oral pathologists, or otolaryngologists for treatment, he said.

This study was funded by the National Cancer Institute. Dr. Rhodus and Dr. Greenspan have disclosed no relevant financial relationships.

International Association of Dental Research (IADR) 89th General Session and Exhibition: Abstract 945. Presented March 17, 2011.

Tongue cancer symptoms: soreness, spots & swellings

Author: staff

Tongue cancer normally occurs in the squamous, or skin cells. Symptoms of tongue cancer either in the front or middle of your tongue makes it oral cancer – if they’re at the base of your tongue it comes under the heading of throat or oropharyngeal cancer. When looking for tongue cancer symptoms, watch out for the following persistent signs:

• Red, pink, grey or white spots on tongue
• Sore spots on tongue
• Leukoplakia or erythroplakia on tongue
• Sore throat
• Pain when swallowing
• Mouth numbness
• Unexplained bleeding of tongue
• Pain in the ear (very rare)
• Changes in your voice
• Tongue swelling

Red, Pink, Grey or White Spots on Tongue – These symptoms of tongue cancer start small and may look like canker sores, especially if they occur in other places in your mouth. Canker sores tend to go away in a week or two.

White spots on tongue might also indicate oral thrush or hairy tongue, but you’ll be able to gently scrape these off yourself. Remember, persistency is one of the main factors for symptoms of tongue cancer, along with tongue pain.

Leukoplakia & Erythroplakia – These are products of uncontrolled cell growth, one of the very definitions of cancer. But figuring out if they are actual tongue cancer symptoms or just irritations from your dental work depends on a biopsy. They might also be pre-cancerous, so it’s best to see your dentist about these swelling or thickening patches right away.

Pain, Numbness & Bleeding – If you’re getting a burning sensation, it’s possible you suffer from burning mouth syndrome or geographic tongue rather than cancer. Sharp tongue pains and persistent soreness are more dangerous. And persistent sore throat pain is one of the oropharyngeal tongue cancer symptoms.

Watch for easy bleeding should you happen to bite your tongue or if you merely touch a trouble spot. (But oral thrush patches might also bleed if you try to remove those.)

Tongue pain, swelling and numbness as symptoms of tongue cancer could indicate that the disease moved deeper into your nerve cells. And tongue swelling may be a symptom of other, non-oral cancers.

More Tongue Pain Considerations

When you see or feel possible tongue cancer symptoms and begin wondering about tongue cancer treatments, ask yourself these questions:

1. Do you use tobacco in any form? Does your tobacco use go hand-in-hand with alcohol use?
2. Are you over age 40?
3. Are you a male?
4. Are you of African-American descent?

If you spot potential symptoms of tongue cancer, and answered yes to any or all of the above questions, you should have a dentist do a checkup immediately. The American Dental Association (ADA) says people who use alcohol or tobacco (especially together), people over 40, and especially African-Americans, tend to be at higher risks for mouth and throat cancers. (As more and more women take up smoking, the gender gap in oral cancer risks decreases.)

The Bottom Line
About 25 percent of oral cancer patients have no risk factors at all, according to the ADA. Throat or tongue pain, bleeding and numbness; discolorations like white spots on tongue, swellings, patches or sores of any type should be monitored as potential tongue cancer symptoms. And if they occur elsewhere in your mouth, they might indicate other oral cancers.

If the symptoms last more than a week or two, see your dentist. They might not be symptoms of tongue cancer at all, but it’s better to be safe and gain some peace of mind. And if they’re not, you may just need adjustments to your dentures, dental crowns, fillings or some anti-fungal medications.

Clinical significance of phosphatidyl inositol synthase overexpression in oral cancer

Authors: Jatinder Kaur et al.

We reported increased levels of Phosphatidyl Inositol synthase (PI synthase), (enzyme that catalyses phosphatidyl inositol (PI) synthesis-implicated in intracellular signaling and regulation of cell growth) in smokeless tobacco (ST) exposed oral cell cultures by differential display. This study determined the clinical significance of PI synthase overexpression in oral squamous cell carcinoma (OSCC) and premalignant lesions (leukoplakia), and identified the downstream signaling proteins in PI synthase pathway that are perturbed by smokeless tobacco (ST) exposure.

Tissue microarray (TMA) Immunohistochemistry, Western blotting, Confocal laser scan microscopy, RT-PCR were performed to define the expression of PI synthase in clinical samples and in oral cell culture systems.

Significant increase in PI synthase immunoreactivity was observed in premalignant lesions and OSCCs as compared to oral normal tissues (p=0.000).

Further, PI synthase expression was significantly associated with de-differentiation of OSCCs, (p=0.005) and tobacco consumption (p=0.03, OR=9.0). Exposure of oral cell systems to smokeless tobacco (ST) in vitro confirmed increase in PI synthase, Phosphatidylinositol 3-kinase (PI3K) and cyclin D1 levels.

Collectively, increased PI synthase expression was found to be an early event in oral cancer and a target for smokeless tobacco.

Authors: Jatinder Kaur, Meenakshi Sawhney, Siddartha Datta, GuptaNootan, Shukla, Anurag, Srivastava, Ranju Ralhan

Source: BMC Cancer 2010, 10:168

Dentists your first defence in fight against oral cancer

Source: Timescolonist

Author: Johnathan Skuba

In 2003, an estimated 3,100 Canadians were newly diagnosed with oral cancer. That same year, 1,090 people died of the disease. In the U.S., oral cancer kills roughly one person per hour, 24 hours a day. Of those newly diagnosed, only half will survive five years later, and this terrifying death rate has not declined for decades.

Those statistics are frightening, but the good news is that early detection plays a major role in preventing or curing oral cancers. The first line of defence is the dentist. They are specifically trained to recognize even subtle changes in the mouth and take action.

Pre-malignant lesions usually manifest as white patches (leukoplakias) that can look like small calluses. They could be benign and nothing but skin thickened by trauma or normal wear and tear of oral tissues. Of greater concern are spots that become ulcers, bleed, rapidly change appearance or that are obviously getting larger. Red patches (erythroplakia) should also be examined as they too could represent cancerous tissue. If any such spots are present and either enlarge or don’t improve within 10-14 days, or if they disappear and then recur, patients are advised to see their dentists as soon as possible.

Once in the chair, patients will find that dentists do not take chances, especially when the spots appear in areas where normal trauma is unlikely, such as the soft palate of the mouth or under the tongue. When such spots are seen, and particularly when there is no known cause, the dentist will strongly recommend followup and refer the patient to an oral pathologist or an oral and maxillofacial surgeon for consultation and possible removal and biopsy. If the dentist believes that the lesion is likely not cancerous but still a possible concern, they may choose to closely monitor the area over a short time and make a referral if it remains suspicious upon followup.

“The best thing is to remove all suspicious lesions,” says Dr. Seema Ganatra, an oral pathologist who teaches at the University of Alberta. “Oral cancer has a similar progression to many other cancers such as cervical cancer. When dysplasia (abnormal cells) is seen, these cells may evolve into cancer cells if they are not removed. It is impossible to predict which lesions will go on to become cancer. Followup screening and patient education complete the cycle.”

Regular dental checkups are essential to protect one’s health, since early detection can save lives. Reducing risk factors is another way to promote good health, Ganatra says.

“Not surprisingly, people who smoke are at high risk for oral cancer, but so are those who consume large amounts of alcohol. People who are both heavy smokers and drinkers have 18 times the risk of developing oral cancer.”

Smokeless tobacco, cigars and pipe smoking are every bit as dangerous as cigarettes, she adds. And those with these increased risk factors who don’t regularly see a dentist face even greater peril.

“By the time their symptoms worsen enough for them to seek medical help, they are usually in the advanced stages of the disease.”

At present, 95 per cent of oral cancers are found in people over 45, but an alarming trend points to younger people getting the disease from another source. In people who don’t smoke or drink, there is a rise in oral cancer (and certain other cancers) due to specific strains of the human papilloma virus (HPV), a sexually transmitted infection most commonly associated with genital warts. According to the Oral Cancer Foundation, HPV-linked oral cancer is the fastest-growing segment of the oral cancer population.

Dentists have a number of screening tools such as rinses and fluorescent lights to help them spot signs of oral cancer, but visual diagnosis and biopsy remain the best detection methods, Ganatra says. “It is in the pathology lab that we have a better chance of making the diagnosis.”

Public awareness is key to lowering the incidence of oral cancer. Reduce or remove risk factors like tobacco, alcohol and unprotected sexual activity. Have regular dental checkups and schedule another appointment if you see unusual spots in your mouth or experience symptoms like fatigue or a hoarse throat in the absence of a cold or flu. Follow your dentist’s advice on prevention and treatment.

“Screening is vital,” says Ganatra. “Two-thirds of oral cancers are found in the late stages; if we had caught them early, those people might still be alive.”

Dr. Jonathan Skuba is a past president of the Alberta Dental Association and College. He has been in general practice in Edmonton since 2001.

Understanding the link between HPV and oropharyngeal cancers

Source: (Journal of the American Academy of Physician Assistants, October, 2009)
Authors: Denise Rizzolo, PA-C, PhD, Mona Sedrak, PA-C, PhD

Head and neck cancer is diagnosed in approximately 650,000 patients each year worldwide.1 The term head and neck cancer refers to a group of biologically similar cancers originating from the upper aerodigestive tract, including the lip, oral cavity (mouth), nasal cavity, paranasal sinuses, pharynx, and larynx. Oropharyngeal refers to all the structures of the mouth and pharynx, including the tonsils and tongue. Oral squamous cell carcinoma (OSCC) is the most common form of head and neck cancer.2 Seventy-five percent of all OSCCs are attributable to tobacco and alcohol use.3 People who smoke cigarettes are 4 times more likely to develop oral cancer than nonsmokers. Furthermore, individuals who consume alcohol are 3 times more likely than nondrinkers to develop oral cancer.3 According to the Substance Abuse and Mental Health Services Administration, the prevalence of cigarette smoking has decreased among Americans, and alcohol use has also declined since the 1970s.4,5 However despite this, the incidence of oropharyngeal cancers, including cancer of the base of the tongue and tonsils, has increased, especially in younger patients. These trends have led researchers to investigate other potential risk factors.6-8

New studies suggest that there may be an alternative pathway for the development of oropharyngeal cancers. The high-risk types of human papillomavirus (HPV), especially type 16 (HPV-16), are now thought to be potential etiologic agents.2,3 The concept that HPV plays a role in head and neck cancers is not new. This link has been under investigation for at least 20 years.6 This is a worrisome public-health concern because patients with HPV-positive OSCC are 3 to 5 years younger at diagnosis than those with HPV-negative OSCC, and they have a history of high-risk sexual behavior.9-12 Interestingly, patients with HPV-positive OSCC are also less likely to have a history of alcohol and tobacco abuse.3 Therefore, educating patients regarding the disturbing trend of HPV-positive oropharyngeal cancer is important.

Incidence and Prevalence
In the United States alone, an estimated 34,360 people received a diagnosis of oropharyngeal cancer in 2007; of these, 7,550 (5,180 men and 2,370 women) died.13 On average, more than 25% of people who develop oropharyngeal cancer will die of the disease, with only 60% surviving for more than 5 years.14 In fact, oropharyngeal cancer is as common as leukemia and claims more lives than either melanoma or cervical cancer.13

Since the mid 1970s, oropharyngeal cancer rates have increased approximately 15%, with significant disparities in some population groups. For instance, oropharyngeal cancer prevalence is significantly higher in males than in females.14 Prevalence is also higher in Hispanic and black males than it is in white males.14 The risk of oropharyngeal cancer increases with age, and occurrence is highest in persons older than 50 years and peaks between ages 60 and 70 years.14 However, there has been a startling 5-fold increase in the incidence of oral cancer in patients younger than 40 years, many of whom have no known risk factors.4

HPV is associated with 15% to 35% of head and neck cancers worldwide.11 Fifty percent to 90% of OSCCs in the pharynx, tonsil, and tongue are HPV-positive.11 Chaturvedi and colleagues investigated the impact of HPV on the epidemiology of OSCCs in the United States.9 These researchers reported that HPV-positive OSCCs were diagnosed at younger ages than HPV-negative OSCCs (mean age at diagnosis was 61.0 and 63.8 years, respectively) and the incidence increased significantly for HPV-positive OSCC from 1973 to 2004, particularly among younger white men.

Kreimer and colleagues conducted a systematic review of 60 studies and determined that 25.9% of the 5,046 patients with head and neck squamous cell carcinoma (HNSCC) were HPV-positive.2 Furthermore, these researchers noted that HPV-16 was the most prevalent genotype in these cancers, accounting for 86.7% of cases.

Although there is research that supports the association between HPV and oropharyngeal cancers, some studies dispute that relationship. Specifically, controversy exists over the prevalence and significance of HPV in oral tongue cancers (cancer of the anterior two-thirds of the tongue). In a 2008 Mayo Clinic study, researchers examined fresh-frozen tissues from 51 patients with oral tongue cancers.15 Their findings suggest that the incidence of oral HPV in oral tongue cancer was low and was unlikely to play a significant role in the etiology, pathogenesis, and clinical outcomes of oral tongue cancers.15 The authors admit the study was limited by a small sample size and that more research is needed.

The oropharyngeal sites that are most often associated with the HPV infection are the tonsils and the tongue.16,17 Reasons why the oropharynx is more susceptible to the HPV infection remain unclear; however, the similarity in accessibility to infection between the tonsillar tissue and the uterine cervical mucosa is believed to make the oropharyngeal area more vulnerable. Another explanation is that tonsillar tissue contains deep invaginations that may capture the virus and facilitate it into the basal cells.

The mechanism of HPV carcinogenesis was first characterized in cervical cancer. Ninety percent of cervical cancer cases are related to HPV infection, predominantly HPV-16 and HPV-18.18 The viral oncoproteins E6 and E7 of the high-risk HPV types are associated with the malignant process in both anogenital and head and neck cancers.17 These oncoproteins inactivate the p53 and pRb tumor suppressor pathways, which is important to the genetic progression of head and neck cancers. HPV infection may therefore represent an alternate but functional pathway for HNSCC pathogenesis. Yet, despite recent literature confirming that HPV is a risk factor associated with oropharyngeal cancers, the HPV infection is not necessary nor is it sufficient for oropharyngeal carcinoma to develop. Therefore, more research is needed to closely define the link between the acquisition of the virus and the progression to cancer.

The major prognostic factors for head and neck cancer are the presence of local and regional metastasis, vascular or lymphatic invasion, positive surgical margins, and extracapsular spread of tumor cells from the lymph nodes into the soft tissue of the head and neck.19 Thus, understanding the mechanism of tumor progression may help to identify new prognostic and predictive markers that will aid in the development of new therapeutic agents for the treatment of HPV-positive cancer.20

Incidence of HPV Transmission
The association between high-risk sexual behavior and transmission of HPV is well-established.10,21 Certain sexual behaviors are associated with a significantly increased risk of HPV transmission, including engaging in casual sex, young age at first intercourse, and infrequent use of condoms. Specifically, a high number of lifetime sex partners (26 or more vaginal-sex partners, 6 or more oral-sex partners) is associated with an increased risk of oropharyngeal cancer. A study conducted from 2000 to 2006 positively correlated HPV-16-positive cancer of the head and neck with number of oral-sex partners, as well as with marijuana use.22

Diffuse white area on the buccal mucosa

Diffuse white area on the buccal mucosa

The onset of the HIV epidemic has resulted in an increase in oral sex practices among teenagers and young adults, which may be contributing to the increase in the incidence of HPV-positive cancers.23 A common belief among people in these age-groups is that oral sex represents a form of “safe sex,” leading to a worry-free behavior that precludes them from contracting sexually transmitted diseases. These findings emphasize a significant implication to public health. The increase in the incidence of tonsillar and base-of-tongue cancers in the United States may be a result of a higher incidence of oral-sex practices.7,8

Clinical Signs and Symptoms
HPV-positive oropharyngeal cancer manifests in the same manner as HPV-negative oropharyngeal cancer. Therefore, clinicians should be aware of the signs and symptoms that suggest OSCC. Patients present with a variety of signs and symptoms depending on the site of origin, including a sore throat, dysphagia, odynophagia, and hoarseness14 (Table 1). The two precursor lesions clinicians should look for are leukoplakia, white lesions (Figure 1), and erythroplakia, red lesions. Although leukoplakia lesions are more common, erythroplakia and lesions with erythroplakic components have a much greater potential for becoming cancerous. Any white or red lesion that does not resolve within 2 weeks should be reevaluated and considered for biopsy to obtain a definitive diagnosis.14 The following are the four basic steps to early detection and prevention of disease:

• Take a thorough history
• Perform a detailed examination of the head and neck
• Educate patients on the risk factors associated with oral cancers
• Provide adequate follow-up to ensure a definitive diagnosis of any suspicious lesions.14


A thorough history and physical examination of the head and neck should be a routine part of each patient’s general medical examination. Clinicians should be particularly vigilant when examining patients who have a history of tobacco use or drink excessive amounts of alcohol. The examination is conducted with the patient seated. The patient should remove any intraoral prostheses before beginning the examination. The extraoral assessment includes inspection of the face, head, and neck; note any asymmetry or skin pathology, such as crusts, fissuring, growths, and/or color changes. The regional lymph node areas are bilaterally palpated to detect any enlarged nodes.14 The perioral and intraoral examination follows a detailed, seven-step systematic assessment14 (Table 2).


Recent data suggests a better prognosis for those patients with HPV-positive HNSCC than for those with HPV-negative HNSCC; however, there is still intense debate over this theory.20 Treatment is the same for patients, regardless of whether they have HPV-positive or HPV-negative HNSCC. Traditional therapy for patients with stage I or II head and neck cancer consists of radiation and/or surgery, and prognosis is excellent. Unfortunately, most patients present with stage III or IV disease, and treatment consists of a combination of chemotherapy, radiation, and surgery.20 Survival rates are greatly diminished when the disease is diagnosed at a later stage.

An interesting note is that research suggests that HPV-positive tumors behave in a different fashion, have a different response to therapy, and are more sensitive to radiation-based therapies; therefore, HPV-positive HNSCCs may require a different therapeutic approach compared with HPV-negative HNSCCs.24 Fakhry and colleagues found that patients with HPV-positive HNSCC had better overall and progression-free survival rates than did patients with HPV-negative HNSCC.24 These findings raise the question of whether traditional therapy is the best option for HPV-positive disease. Even when HNSCC is diagnosed early, treatment still consists of removal of the diseased tissue and/or weeks of radiation therapy that may leave some patients disfigured or with permanent negative sequela (dry mouth, loss of taste, alteration of speech patterns, etc). If HPV-positive cancers are more sensitive to traditional therapy, can less aggressive and extensive treatment be used thereby minimizing the side effects of current therapeutic regimens on this subset of patients? The study authors interpret their results cautiously, suggesting that more research is needed on treatment response and subsequent survival patterns of patients with HPV-positive cancers. Until further research is conducted, therapeutic treatment strategies are the same for HPV-positive and HPV-negative HNSCC.24

Patient Education: Prevention and Detection
The best way to prevent oropharyngeal cancer is to avoid tobacco and alcohol use. In addition, regular dental checkups, including an examination of the entire mouth, are essential for early detection of cancerous and precancerous conditions. Red or white lesions often precede the development of oropharyngeal cancer; therefore, if patients notice any new lesions in their mouths, they should have them evaluated by their clinicians. Lesions that do not resolve after 2 weeks should be biopsied. Detection of oropharyngeal carcinoma while the disease is still localized can dramatically increase survival rates. The 5-year survival rate for patients with localized disease at diagnosis is 82%, compared with only 28% for those whose cancer has spread to other parts of the body.14

Clinicians should take the time to educate young patients regarding HPV infection, its correlation to oropharyngeal cancer, and safe-sex practices. Some discussions in the literature suggest that the HPV vaccine could be considered for the prevention of HPV-positive HNSCC.6,10,20 The HPV vaccine has become an important strategy in the prevention of cervical cancer because HPV has been shown to cause nearly all cases of female cervical cancer. Ninety-five percent of patients with HPV-positive HNSCC are positive for HPV-16; therefore, researchers are exploring whether the vaccine could provide the same prophylactic effect against HPV-positive HNSCC as it does for HPV-associated anogenital cancers.25 D’Souza and colleagues argue that a rationale for HPV vaccination in both boys and girls is that oropharyngeal cancers occur in both men and women.10 They also suggest that if the vaccine prevents oral disease as effectively as it prevents cervical disease, a substantial reduction in the incidence of oropharyngeal cancer in vaccinated populations would provide the ultimate evidence of causality. However, no definitive recommendations to use the HPV vaccine to prevent HPV-positive HNSCC have been made.


Cancers of the head and neck are a worldwide concern. The incidence of HPV-related head and neck cancer is increasing. Clinicians should be aware of the risk factors as well as the clinical signs and symptoms of oropharyngeal cancers. The best way to prevent oropharyngeal cancer is to avoid tobacco and alcohol use. However, consistent safe-sex practices are also effective preventive measures because of the strong correlation between HPV infection and oropharyngeal cancers. This association has researchers considering the potential effectiveness of the HPV vaccine in the prevention of HPVpositive head and neck cancers. JAAPA

Authors’ affiliations
Mona Sedrak is an associate professor in the PA program at Seton Hall University, South Orange, New Jersey. Denise Rizzolo works at the Care Station, Springfield, New Jersey, and is faculty assistant professor in the PA program at Seton Hall University. They have indicated no relationships to disclose relating to the content of this article.

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Involvement of potential pathways in malignant transformation from oral leukoplakia to oral squamous cell carcinoma revealed by proteomic analysis

Author: staff

Oral squamous cell carcinoma (OSCC) is one of the most common forms of cancer associated with the presence of precancerous oral leukoplakia. Given the poor prognosis associated with oral leukoplakia, and the difficulties in distinguishing it with cancer lesion, there is an urgent need to elucidate the molecular determinants and key signal pathways underlying the malignant transformation of precancerous to cancerous tissue, and thus to identify novel diagnostic and therapeutic target.

We have utilized two dimensional electrophoresis followed by ESI-Q-TOF-LC-MS/MS to identify proteins differentially expressed in six pairs of oral leukoplakia tissues with dysplasia and oral squamous cancer tissues, each pair from the same patient.

Approximately 85 differentially and constantly expressed proteins (>two-fold change, P>0.05) were identified, 52 up-regulated and 33 down-regulated. Gene ontological methods were employed to identify the biological processes that were over-represented in this carcinogenic stage.

Potential biological networks were also constructed to reveal the link between those protein candidates. Among those proteins, three homologs of proteosome activator PA28 a,b and g were shown to have up-regulated mRNA levels in OSCC cells relative to oral keratinocytes.

Amounts of differentially expressed proteins involved in the malignant transformation of oral leukoplakia.

Their expression level, bioprocess, interactions networks could be analyzed by bioinformatics approach. All the three homologs of PA28 may be shown to play an important role in the malignant transformation.

Our study is an example of a systems biology study, in which functional proteomics was constructed to help to elucidate mechanistic aspects and potential involvement of proteins. Our results may provide new insights into the pathogenesis of oral cancer.

These differentially expressed proteins may have utility as useful candidate markers of OSCC.

BMC Genomics 2009, 10:383

Wang Zhi, Feng Xiaodong, Liu Xinyu, Jiang Lu, Zeng Xin, Ji Ning, Li Jing, Li Longjiang, Chen Qianming

New products ingenious or insidious?

Author: John Darling

The use of smokeless tobacco in Jackson County has steadily risen in recent years among teens and adults — and now, officials fear the introduction earlier this year of new, candy-flavored “dissolvable tobacco” lozenges will make matters worse.

Called Orbs, the pellets, which look and taste like breath mints, contain as much nicotine as a cigarette and could cause cancer of the mouth and throat, said Jane Stevenson, tobacco program coordinator for the county.

Among eighth-grade males in Jackson County, use of smokeless tobacco jumped from 2 percent in 2001 to 7 percent in 2006, reported Stevenson. Among 11th-grade males, it rose from 10 percent in 2001 to 16 percent in 2006. Among adults here, 3 percent use smokeless tobacco. These figures are 1 to 4 percent higher than the state rates.

“The increase of smokeless tobacco use here among teens is significant and alarming — and dissolvable tobacco is just as addictive as smoking,” said Stevenson. “They are packaged to look hip and trendy and they carry the Camel logo. Usually, people are very loyal to their tobacco brand.”

The introduction of dissolvable tobacco pellets is in response to new laws prohibiting smoking in bars, restaurants and the workplace, said Mike Welch, owner of Puff’s Magazine & Fine Tobacco, an Ashland smoke shop.

The target market for dissolvable pellets, Welch added, is people who buy low-end generic cigarettes. His store won’t be selling them, he said, because too many of his customers are concerned about throat cancer.

Talent police in May warned parents about the product after finding several Talent Middle School children with them. Like cigarettes, dissolvable tobacco can be sold only to people 18 and older — but the kids got it from an older sibling, to whom it came as a free promo with cigarettes, said Talent Police Chief Mike Moran.

“You may not get the lung damage and you hear justifications about it, that adults don’t have to go stand outside to smoke,” Moran said, “but I think it’s a bad product, insidious, with high concentrations of nicotine, designed to look like candy — and it’s something no person under 18 should have any use for.”

Food 4 Less in Medford reported the product is not very popular and that people who buy them — just under $5 for 18 pellets — usually are taking advantage of coupons from magazines or other Camel products.

Dissolvable tobacco can raise blood pressure and pulse and cause heartburn, digestive problems and bad breath, Stevenson said.

Within two years, side effects can include white precancerous spots, called leukoplakia, in the mouth, tooth-staining and decay, and gum-recessing and disease.

Long-term impacts, she said, can be cancer of the mouth, throat, larynx, esophagus or stomach, heart disease, stroke and tooth loss.

The Centers for Disease Control and Prevention in Atlanta reports that smokeless tobacco contains 28 carcinogens. About 3 percent of Americans use smokeless tobacco, with use highest among males, American Indians and blue-collar workers. More than a $250 million is spent annually promoting it, the CDC reports.

Stevenson said the lozenges present a new concern because, being smokeless and spit-free, they can be used in classrooms without being readily detected.

Some smokers consider them less harmful than cigarettes and are using them to kick smoking, she said, but “they are just as addictive.”

U.S. Sen. Jeff Merkley, D-Ore., wrote an amendment to the Family Smoking Prevention and Tobacco Control Act requiring the newly created Tobacco Products Scientific Advisory Committee to study the health effects of dissolvable tobacco candy products and report its findings to the Food and Drug Administration.

“In response to a drop in the number of cigarette smokers and new laws limiting smoking in public, Big Tobacco has resorted to outrageous tactics to hook a new generation of our children on tobacco,” Merkley said in a news release.

“The tobacco companies are trying to portray new dissolvable tobacco products as harmless, but the truth is that smokeless tobacco is not safe tobacco. Tobacco candy causes cancer and kills,” he said.

The Campaign for Tobacco-Free Kids said, “They are likely to appeal to children because they are flavored and packaged like candy, are easy to conceal even in a classroom, and carry the Camel brand that is already so popular with underage smokers.”

R.J. Reynolds, which makes Camels, is due to come out with dissolvable tobacco strips and toothpick-like sticks, according to industry Web sites.

“This is the future,” Stevenson said. “We’re going to see more and more of this product for people addicted to nicotine — and gram for gram, nicotine is more addictive than any substance.”

Stevenson added that with the shifting of tobacco regulation to the FDA, “they’ll have to let us know what’s in them.”

A noninvasive genetic screening test to detect oral preneoplastic lesions

Source: Laboratory Investigation (2005) 85, 1481–1488. published online 29 August 2005
Authors: Jantine F Bremmer et al.

Early diagnosis of oral squamous cell carcinoma (OSCC) may have a major impact on survival and quality of life. Recent studies have shown that the majority of OSCC is preceded by precursor lesions characterized by genetic alterations. The aim of this study was to develop and evaluate a noninvasive screening test for oral preneoplastic lesions, based on genetic alterations as marker.

Various methods to obtain a high yield of cells by brushing a small area of the oral mucosa were compared. A novel genetic assay, multiplex ligation-dependent probe amplification (MLPA), was applied that enables the measurement of gains and losses at 40 different chromosomal locations in one PCR reaction using 150 ng DNA. MLPA was performed on DNA of normal and dysplastic oral mucosa as well as of OSCC with the intention to select a specific probe set for accurate detection of precursor lesions in the oral cavity.

The assay was correlated to loss of heterozygosity analysis using microsatellite markers, and evaluated on noncancer subjects and patients with oral leukoplakia. A noninvasive sampling method was developed with DNA yields ranging from 150 to 600 ng. Using 120 probes, we could detect large differences with MLPA in the number of alterations between normal vs dysplastic and dysplastic vs tumor tissue with P-values <0.001.

A significant correlation was found between the number of alterations as detected by MLPA and the analysis for allelic loss. The available data enabled the selection of a set of 42 MLPA probes, which had the power to optimally discriminate between normal and dysplastic tissue. Our data show that MLPA is a sensitive, reliable, high-throughput and easy-to-perform technique, enabling the detection of genetic alterations on small noninvasive samples and can be considered a promising method for population-based screening of preneoplastic lesions in the oral cavity.

Jantine F Bremmer1, Boudewijn J M Braakhuis2, Henrique J Ruijter-Schippers1,2, Arjen Brink1,2, Helena M B Duarte3, Dirk J Kuik4, Elisabeth Bloemena1, C René Leemans2, Isaäc van der Waal1 and Ruud H Brakenhoff2

Authors’ affiliations:
1Department of Oromaxillofacial Surgery and Oral Pathology, VU University Medical Center, Amsterdam, The Netherlands
2Department of Otolaryngology/Head-Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands
3MRC-Holland, Amsterdam, The Netherlands
4Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands

2009-02-07T13:21:08-07:00February, 2009|Oral Cancer News|

Screening for oral precancer with noninvasive genetic cytology

Source: Cancer Prevention Research, 10.1158/1940-6207
Authors: Jantine F. Bremmer et al.

Oral squamous cell carcinomas develop in precancerous fields consisting of genetically altered mucosal epithelial cells. These precancerous fields may appear as clinically visible lesions, in particular, oral leukoplakia, but the large majority remains clinically undetectable. The aim of this study was to assess the potential value of a noninvasive screening approach to detect precancerous fields.

As a first step, we developed a suitable assay and investigated 25 leukoplakia patients and 20 noncancer control subjects. Exfoliated cells were removed by a brush from multiple small areas of the oral mucosa, including the leukoplakia. Brushed samples were investigated for allelic imbalance (AI) at chromosomes 3p, 9p, 11q, and 17p using microsatellite markers known to show frequent alterations in oral precancer.

AI was absent in all (137) of the samples of the 20 control subjects, yielding a specificity of 100%. AI was detected in exfoliated cell samples of 40% (10 of 25) of the leukoplakia lesions studied. Genetic changes were also found outside the leukoplakia lesions. Most frequent was AI at 9p (9 of 10). The noninvasive assay was validated against the biopsy results of the leukoplakia lesions yielding an estimate of sensitivity of 78% (7 of 9) and a positive predictive value of 100% (7 of 7).

Altogether, these results show the feasibility of a noninvasive genetic screening approach for the detection and monitoring of oral precancer. This assay could therefore contribute to the secondary prevention of oral squamous cell carcinoma. The assay also shows promise for the detection of precancerous changes that are not macroscopically visible.

Jantine F. Bremmer1,4, A. Peggy Graveland2, Arjen Brink1,2, Boudewijn J.M. Braakhuis2, Dirk J. Kuik3, C. René Leemans2, Elisabeth Bloemena1,4, Isaäc van der Waal1,4 and Ruud H. Brakenhoff2

Authors’ affiliations:
Departments of 1 Oral and Maxillofacial Surgery and Oral Pathology, 2 Otolaryngology/Head-Neck Surgery, and 3 Clinical Epidemiology and Biostatistics, VU University Medical Center, and 4 ACTA, Amsterdam, the Netherlands

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