Monthly Archives: March 2009

High dosage brachytherapy obtains excellent results in head and neck tumors

Author: staff

High-dosage perioperative brachytherapy (applied within the surgical process) obtains excellent results in the treatment of head and neck tumours, at the same time as reducing the period of radiation. These are the conclusions of research undertaken jointly by three Departments at the University of Navarra Hospital and which was published in the latest issue of Brachytherapy, official journal of the American Society of Brachytherapy.

The work describes the application of this new radiotherapy technique to 40 patients between 2000 and 2006. Given the size of the sample, the article is a description of the greatest number of patients treated with high-dosage brachytherapy for head and neck tumours in world medical literature. According to results, after a seven-year follow-up, the illness was controlled in 86% of the cases and the percentage of survival was 52%.

In concrete, the research focused on the treatment of tumours in the oral cavity, those affecting the tongue and the floor of the mouth, and those in the oropharyngeal region, such as tumours of the tonsils.

Involved in the study was a multidisciplinary team of seven specialists from three departments at the University of Navarra Hospital: the Radiotherapy Department, the Department of Oral and Maxillofacial Surgery and the Ear, Nose and Throat Department.

Intensifying radiation dosage
As is known, brachytherapy is a radiotherapy treatment involving the placing of radioactive sources within the tumour or nearby.

In the case in hand, the work analysed the application of brachytherapy as complementary post-surgery treatment, explained Doctor Rafael Martínez-Monge, Director of the Radiotherapy Department. Some cases of head and neck tumours require the application of radiotherapy after the surgical operation. Using this technique, they have managed to intensify the radiation dosage with the goal of reducing relapse rates.

In certain treatments, brachytherapy provides better end-result possibilities than conventional radiotherapy. The procedure enables the administration of doses that would not be easily achieved using other techniques, due to toxic effects, explained the specialist from the University of Navarra Hospital.

Two weeks of treatment less
Moreover, the use in brachytherapy of high dosages involves a series of benefits for the patient as regards the overall treatment. The great advantage, points out Doctor Martínez-Monge, is the reduction of total time. While conventional radiotherapy treatment lasted seven weeks, administering part of the radiation through brachytherapy can take two weeks less.

This technique also manages to reduce the time of radiation compared to treatment with low dosage brachytherapy. Thanks to the existence of new sources of radiation, the treatment is released in a matter of minutes. Before the patient under brachytherapy treatment carried the radioactive source for several days and, thus, had to be isolated in a lead-lined room, with limitations on visits and nursing care. With high-dosage brachytherapy, however, the patient is only radioactive during the actual administration of the treatment; as such, the rest of the time can be spent in a conventional room.

For the administration of this technique it is necessary to prepare the affected region during the surgical operation. On extirpating the tumour, the surgeon covers the surgery zone — the area with greatest possibilities for relapse — with a series of plastic tubes which are subsequently filled with radioactive material, the aim being to effect a highly selective and precise radiation. Brachytherapy is introduced through these tubes, one end of which appears at the surface of the skin, like a drainpipe, explained Doctor Rafael Martínez-Monge. These tubes are connected to a machine that administers the treatment according to a computer programme personalised for each patient, he added.

Application to other types of tumour
Apart from perioperative high-dosage brachytherapy treatment for head and neck tumours, the University of Navarra Hospital has been working on the application of this procedure to other oncological processes for a number of years. There are a number of studies under way on its use in gynaecological tumours and sarcomas, amongst others. Since 2000 about 400 patients, with different types of tumours, have been treated with this technique.

March, 2009|Oral Cancer News|

Genetic Changes Outside Nuclear DNA suspected to trigger more than half of all cancers

Author: staff

A buildup of chemical bonds on certain cancer-promoting genes, a process known as hypermethylation, is widely known to render cells cancerous by disrupting biological brakes on runaway growth. Now, Johns Hopkins scientists say the reverse process — demethylation — which wipes off those chemical bonds may also trigger more than half of all cancers.

One potential consequence of the new research is that demethylating drugs now used to treat some cancers may actually cause new cancers as a side effect.

“It’s much too early to say for certain, but some patients could be at risk for additional primary tumors, and we may find that they need a molecular profile of their cancer before starting demethylating therapy,” says Joseph Califano, M.D., professor of otolaryngology–head and neck surgery and oncology at Johns Hopkins.

The findings, based on studies of normal and cancer cells from human mouth, nose and throat tissue, provide more evidence that important regulators of gene activity occur outside as well as inside DNA in a cell’s nucleus.

“While cancer-causing and other mutations alter vital protein-making pathways by rewriting the gene’s DNA code, epigenetic changes affect genes without changing the code itself. The new studies tell us that such changes occur not only when methyl groups bond to a gene’s on-off switch, but also when they come unglued,” says Califano.

Califano says sporadic reports of demethylation as a tool in activating cancer-promoting genes led his team to develop a systematic way to discover these epigenetic changes and show how the process is linked to cancer.

To gather their evidence, Califano and his group treated two cell lines from normal oral tissue with the demethylating drug 5-azacytidine and collected a list of genes that were activated as a result. They used special silicon chips carrying pieces of genetic material that allow thousands of genes to be analyzed at one time to locate genes activated by demethylation.

The list was cross-referenced with genes “turned on” in 49 head and neck cancer samples and 19 normal tissue samples. In all, Califano and his team found 106 genes specific to head and neck cancer that were activated by the demethylation process. “Some of the genes regulate growth, others metabolize sugars and some have already been linked to cancer development,” says Califano, who is director of head and neck cancer research at the Milton J. Dance Jr. Head & Neck Center at Greater Baltimore Medical Center. A report on this work appears on March 23 in PLoS One.

Further analysis by the Johns Hopkins team revealed a single connection among 106 genes: methylation within them is regulated by another gene called BORIS. BORIS acts as a “master regulator,” recruiting other proteins to demethylate a coordinated set of genes and signaling the development of cancer. According to the scientists, nearly 60 percent of a wide range of cancers, including head and neck and lung cancer, have high levels of BORIS expression.

He envisions that agents like 5-azacytidine may need to be combined with a “BORIS blocker,” a drug that has yet to be developed to protect patients who need demethylating therapies.

The research is funded by the Flight Attendant Medical Research Institute, the National Institute of Dental and Craniofacial Research, and the National Cancer Institute.

Research participants included Ian M. Smith, Chad A. Glazer, Suhail K. Mithani, Michael F. Ochs, Wenyue Sun, Sheetal Bhan, Andrew Gray, Chunyan Liu, Steven S. Chang, Kimberly L. Ostrow, William H. Westra, Shahnaz Begum and Mousumi Dhara from Johns Hopkins; and Alexander Vostrov, Ziedulla Abdullaev and Victor Lobanenkov from the National Institutes of Health.

Johns Hopkins Medicine

March, 2009|Oral Cancer News|

HPV data may aid vaccine’s effectiveness

Author: staff

The majority of invasive cervical cancers in New Mexico in the 1980s and 1990s contained DNA from human papillomavirus type 16 (HPV16) and HPV type 18 (HPV18), says a new study.

It also found that women diagnosed with HPV16- or HPV18-positive cancers were an average of five years younger than those diagnosed with cancers associated with other HPV types.

The HPV vaccine (Gardasil) protects against infections caused by HPV16 and HPV18, so the new findings may have implications for future cancer screening programs, the researchers said.

The researchers analyzed U.S. data in the Surveillance, Epidemiology and End Results registry and identified 1,213 cases of in situ cervical cancer diagnosed between 1980 and 1999, as well as 808 cases of invasive cervical cancer diagnosed between 1980 and 1999 in New Mexico.

HPV16 DNA was found in 53.2 percent of invasive cervical cancers, HPV18 DNA was found in 13.1 percent, and HPV45 DNA in 6.1 percent. HPV16 DNA was found in 56.3 percent of in situ cervical cancers, HPV31 DNA in 12.6 percent, and HPV33 DNA in 8 percent.

Patients’ median age at diagnosis of invasive cancer with HPV16 and HPV18 was 48.1 years, and 45.9 years, respectively. Median age at diagnosis of invasive cancer with other HPV genotypes was 52.3 years.

The study is in the March 24 online issue of the Journal of the National Cancer Institute.

“To our knowledge, this is the largest study of its kind conducted in a U.S. population,” wrote a team led by Cosette M. Wheeler, of the University of New Mexico Health Sciences Center in Albuquerque.

“This study of HPV genotypes in New Mexico provides important baseline data for evaluating the effectiveness of nearly implemented HPV-based technologies, HPV vaccines, and HPV screening in the prevention of cervical cancer,” she said. “Moreover, these data can guide the future application of these technologies to maximize the cost-effective, public health benefits of these interventions.”

March, 2009|Oral Cancer News|

A vaccine debate once focused on sex shifts as boys join the target market

Author: Rob Stein

When a vaccine designed to protect girls against a sexually transmitted virus arrived three years ago, the debate centered on one question: Would the shots make young girls more likely to have sex?

Now the vaccine’s maker is trying to get approval to sell the vaccine for boys, and the debate is focusing on something else entirely: Is it worth the money, and is it safe and effective enough?

“We are still more worried about the promiscuity of girls than the promiscuity of boys,” said Susan M. Reverby, a professor of women’s studies and medical history at Wellesley College. “There’s still that double standard.”

The shift in the discussion about Gardasil illustrates the complex interplay of political, economic, scientific, regulatory and social factors that increasingly influence decisions about new types of medical care. For the vaccine, the new dynamic reflects a strategic tack by Gardasil’s critics, growing concern about health-care costs, fears about whether medical treatments are being vetted adequately and stubborn biases about gender, experts say.

“There is the cost, the safety, the boys versus girls,” said Susan F. Wood, a professor of public health at George Washington University. “These are some of the complexities that are going to have to be addressed one way or the other with this vaccine.”

Gardasil protects against the human papillomavirus, the most common sexually transmitted infection. HPV causes genital warts and, in women, can lead to cervical cancer — a disease that strikes about 10,000 American women a year and kills about 3,700.

For males, the vaccine is aimed at protecting against genital warts and less common malignancies that HPV can cause, such as penile and anal cancer, as well as cancer of the mouth and throat. The virus causes at least 250,000 new cases of genital warts and an estimated 7,500 cancers in males each year, causing perhaps about 1,000 deaths. Vaccinating boys and men would also help prevent the spread of the virus to their sexual partners.

“By vaccinating men as well as women, you reduce the amount of virus that is out there that can be transmitted back and forth,” said Richard M. Haupt, who leads the HPV vaccine program at Merck & Co., which makes Gardasil. “Hopefully there will be a benefit not only to men themselves, but to their partners and future partners.”

After the Food and Drug Administration approved the vaccine in 2006 for girls as young as 9, medical authorities recommended that they receive it at age 11 or 12 to protect them before they start having sex. Critics worried that vaccinating children would send a subtle signal that their parents assumed they would become sexually active and that it would give youngsters a false sense of security.

Merck also began an ambitious marketing campaign and lobbying push to persuade states to add the vaccine to the list of those required for children to attend school. But the company eventually abandoned the strategy in the face of an intense backlash from critics who argued that the decision should be left to parents. Although many states considered such mandates, so far only Virginia and the District have imposed one, and Haupt said the company has no plans to pursue that strategy again.

But in December, Merck asked the FDA to approve the vaccine for males ages 9 to 26, and in February it presented the results of a large study that tested the vaccine in men to the federal Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices, in the hopes of winning the panel’s endorsement. The committee’s recommendations influence which vaccines schools require and whether private insurance companies and state programs will pay.

“There would be a tremendous public health benefit to vaccine 11- and 12-year-olds, both boys and girls,” Haupt said.

The Merck study, involving more than 4,000 boys and men ages 16 to 23, showed that the vaccine is about 90 percent effective in preventing infection with four HPV types, as well as genital warts and precancerous lesions, Haupt said.

In preparation for a vote as soon as October, the CDC committee will meet again in June to consider cost-benefit analyses underway at the CDC and elsewhere. The relatively pricey vaccine costs about $500 for three shots and the associated office visits.

“The cost-effectiveness data will be looked at very carefully,” said Lauri Markowitz, who leads the HPV vaccine work group for the CDC. “There is increased interest in taking cost-effectiveness into consideration when considering prevention efforts.”

The American Academy of Pediatrics will also consider cost-effectiveness in deciding whether to endorse Gardasil for boys.

Some question that focus.

“The cost-effectiveness studies are really important, but I don’t think they should be the sole driver of public health policy,” said Gregory D. Zimet, a professor of pediatrics and psychology at Indiana University. “This is a vaccine that principally benefits women’s health. I wonder if it was the reverse, and there was a vaccine for women that helped prevent prostate cancer in men, this would be as much of an issue.”

Groups that initially were critical when Gardasil was introduced for girls say they now want to make sure the decision is left up to parents.

“We do not oppose the development or distribution of the vaccine,” said Peter S. Sprigg of the Family Research Council. “The only concern we have is about proposals to make vaccination mandatory for school attendance. It’s a parental rights issue.”

Little research has been done on parents’ attitudes about vaccinating their sons, but several experts said it would probably be a harder sell.

“For girls, you can go right to protection against cervical cancer. That’s a powerful argument,” said Zimet, who is studying the issue as part of his own research and in studies sponsored by Merck. “For boys, you have to make several arguments. Part of it is an altruistic argument. I think it’s persuasive, but it’s more complex.”

Debbie Stein of Bethesda, whose 15-year-old daughter, Sara, was vaccinated, thinks she would agree to have her 11-year-old son, Ben, get the shots if his pediatrician recommended them.

“My feeling is it’s a serious virus that causes cancer, and there’s no reason not to vaccinate him,” Stein said. “I think it will protect him and protect his wife in the future. I don’t want to see him when he’s 35 or 40 have a wife die of cancer.”

But Agustin Zamora, who lives in the District, worries that Gardasil has not been studied enough to know that it is safe and effective for his 9-year-old son, Marco, and his twin 2-year-olds, Antonio and Joaquin.

“It’s sort of like doing an experiment on people,” Zamora said. “This is something you’re giving to a lot of children. You need many years of study.”

Federal health officials, Merck and others say they are confident that the vaccine is safe. But some experts said they are concerned that there is insufficient evidence about how long Gardasil’s protection will last, whether serious side effects will emerge and whether the relatively modest benefits for boys are worth even the small risks associated with any vaccine.

“There are lots of things about this vaccine we do not know yet,” said Karen K. Smith-McCune of the University of California at San Francisco. “I just want to be the voice in the room saying, ‘What’s the rush to vaccinate in the absence of the best available data?’ ”

Some also question whether the reduction in infections will mean fewer cancers in the future.

“There’s probably enough data to say it probably is effective for the prevention of genital warts. They’re not fun, but they’re not at the same level as cancer or lethal infectious diseases,” said Diane M. Harper, a professor of medicine at the University of Missouri at Kansas City who helped study the vaccine in women for Merck. “This may not be the best use of our resources at this time.”

March, 2009|Oral Cancer News|

Oral health, mouthwashes and cancer – what is the story?

Author: David Conway

Question: What are the lifestyle, occupational and genetic risk factors for head and neck and oesophageal cancers?

Two hospital-based case–control studies were conducted in central and eastern Europe and Latin America.

Case/control selection
Cases and controls were recruited in Moscow (Russia), Bucharest (Romania) and Lodz and Warsaw (Poland) from 1998 to 2002, and from 1998 to 2003 in Buenos Aires (Argentina), La Habana (Cuba) and the Brazilian towns Rio de Janeiro, São Paulo, Pelotas, Porto Alegre and Goiânia. Incident cases of squamous cell carcinoma of the head and neck (oral cavity, pharynx, larynx) and oesophagus, as well as age- (in quinquennia) and sex frequency-matched controls, were enrolled from 1998 to 2003. Control subjects included residents of the study areas for at least 1 year who were admitted to the same hospitals as the cases or in a comparable catchment area (controls in São Paulo were not recruited from oncology hospitals, and population-based controls were enrolled in Warsaw). Controls were hospitalised for prespecified conditions thought to be unrelated to tobacco use or alcohol consumption. Both studies were coordinated by the International Agency for Research on Cancer according to an identical protocol for both case and control recruitment.

Data analysis
Data from the central European and Latin American studies were analysed separately. Multivariable logistic regression models, including terms for oral health indicators, age, sex, education, country (central Europe) or centre (Latin America), tobacco pack–years and cumulative alcohol consumption, were used to obtain odds ratios (OR) and 95% confidence intervals (CI). All oral hygiene indicators and covariates were analysed as categorical variables, except for age, cumulative alcohol consumption, tobacco pack–years, and age when full-time education was completed, which were analysed as continuous variables. Case–control comparisons were made using t tests for continuous variables and chi-square tests for categorical variables; two-sided P values were obtained. Effect modification was assessed by stratifying on smoking (never/ former/ current) and drinking (never/ ever) habit. Heterogeneity between centres was tested.

Risk factors for head and neck cancer, independent of tobacco use and alcohol consumption, were as follows: poor condition of the mouth [central Europe OR, 2.89 (95% CI, 1.74–4.81); Latin America OR, 1.89 (95% CI, 1.47–2.42)]; lack of toothbrush use [Latin America OR, 2.36 (95% CI, 1.28–4.36)], and daily mouthwash use [Latin America OR, 3.40 (95% CI,1.96–5.89]. Missing six to 15 teeth was an independent risk factor for oesophageal cancer [central Europe OR, 2.84 (95% CI, 1.26–6.41); Latin America OR, 2.18 (95% CI, 1.04–4.59)].

These results indicate that periodontal disease (as indicated by poor condition of the mouth and missing teeth) and daily mouthwash use may be independent causes of cancers of the head, neck and oesophagus.

The UK newspapers have recently been full of headlines linking mouthwash to oral cancer, with varying degrees of certainty reported, for example:

“Mouthwash ’causes oral cancer’ and should be pulled from supermarkets, say experts” (from the Daily Mail, 13 January 2009

“Mouthwash linked to cancer” (Daily Telegraph, 11 January 2009

“Mouthwash can raise cancer risk” [3] (Metro, 12 January 2009;

All of these articles have picked up on a recent narrative review of the literature published in Australian Dental Journal,1 whose authors present their own subjective opinion about the evidence for the risks associated with alcohol-based mouthwash. Their review did include – although did not fully represent – the significant research work from the Genetic Epidemiology Group, Genetics and Epidemiology Cluster, International Agency for Research on Cancer (IARC).2 IARC have recently completed a high quality major international multicentre case-control study – including centres from across Europe, Russia, Latin and South America. This study is a concerted pooling effort to obtain substantial numbers of head and neck cancer cases, namely 924 cases and 928 controls in Europe and 2,286 cases and 1,824 controls in Latin America. The study goes much further than mouthwash use, examining a range of oral health and oral hygiene behaviours in relation to head and neck cancer risk.

The key findings are important for the dental profession and for informing public health approaches. For the European data they are:

* poor oral health is associated with an almost threefold increased risk of head and neck cancer;
* but missing teeth; lack of toothbrushing; wearing a denture were all not associated with an increased risk of head and neck cancer in Europe. The European study did not assess mouthwash use; gum bleeding; regular or irregular dental check-ups; using other oral hygiene instruments or using toothpaste. The Australian mouthwash review therefore quotes selectively only the Latin American data in relation to mouthwash – in which a three-fold increased risk was found.

So where does that leave us? Certainly the data are open to debate and further investigation is needed. Lessons around the presentation of data need to be taken on board to avoid the sensational scare mongering headlines. This is particularly important for the way risk is reported and interpreted. There is also little doubt that the role of oral health and oral health behaviours in the aetiology of head and neck cancer has not received the attention it deserves. This is especially of concern given the anatomical proximity and common risk factors associated with both cancer of the head and neck cancer and other oral conditions. Perhaps the reason for this is the accepted mantra that head and neck cancers are only caused by smoking and alcohol consumption. This has been to the detriment of considering other aetiological factors in research.

The role of oral health warrants further investigation and this could include a systematic review and meta-analysis of the world literature and, potentially and ideally, a pooled analysis of the individual patient data. I understand that the International Head and Neck Cancer Epidemiology consortium have this research on their agenda.

1. McCullough MJ, Farah CS. The role of alcohol in oral carcinogenesis with particular reference to alcohol-containing mouthwashes. Aust Dent J 2009; 53: 302–305. | Article |
2. Guha N, Boffetta P, Wunsch Filho V, et al. Oral health and risk of squamous cell carcinoma of the head and neck and esophagus: results of two multicentric case-control studies. Am J Epidemiol 2007; 166: 1159–1173.

Author’s affiliation:
Dental Public Health Unit, Dental School, Medical Faculty, University of Glasgow, Glasgow, Scotland, UK

March, 2009|Oral Cancer News|

Consistent evidence to support the use of xylitol- and sorbitol-containing chewing gum to prevent dental caries

Author: Svante Twetman

Question: Are polyol-containing chewing gums effective in reducing dental decay?


Data Sources
Studies were identified using searches with Medline, the Cochrane Library and Google Scholar.
Study selection

Studies were screened independently and were included if they evaluated the effect of one or more chewing gums containing at least one polyol (xylitol, sorbitol, mannitol or maltitol) on caries development, provided they supplied original data generated by means of a comparative design (experimental or observational) and were published in English. Studies were excluded if only an abstract was available or they described only the pharmacodynamic or pharmacokinetic properties of polyols or did not include a no-treatment arm in the study. Randomised trial quality was assessed using the Jadad scale, and the US Preventive Services Task Force criteria to grade the internal validity of individual nonrandomised studies.

Data extraction and synthesis
Data were extracted independently with only the final outcomes of a study being recorded. It was decided that surface rather than tooth level data would be recorded. Incremental caries was converted to prevented fraction (PF; the proportional reduction in dental caries in experimental groups relative to control groups) for meta-analysis. The studies were grouped according to type of polyol and a separate meta-analysis performed. Data were pooled using both a random and a fixed-effects model and heterogeneity assessed using I2.

Of 231 articles identified 25 studies were initially selected with 19 being included in the review [six randomised controlled trials (RCT) of which four were cluster RCT, nine controlled clinical trials (CCT) and four cohort studies]. Two RCT had a Jadad score of three or higher. The mean preventive fraction for the four main gum types are shown in the table 1, results of all except the sorbitol -mannitol blend were statistically significant. Sensitivity analyses confirmed the robustness of the findings.

Although research gaps exist, particularly on optimal dosing and relative polyol efficacy, there is consistent evidence to support the use of xylitol- and sorbitol-containing chewing gum as part of normal oral hygiene to prevent dental caries.

This is an excellent systematic review performed in a transparent way according to high standards. The PF figures as well as the clinical recommendation are likely to be frequently cited in future publications. The findings, based on 19 articles from 14 study populations with almost 12 000 participants, were consistent but challenge the conclusions of previous reports.1, 2, 3 In contrast with an earlier systematic review,1 the authors used wider inclusion criteria and accepted both randomised controlled trials (RCT) and observational studies. It should be stressed, however, that only a quarter of the papers were assessed as being of high quality. For example, none of the six RCT was randomised at subject level , and the only paper appraised to be of good quality exhibited marked socio-economic differences between the experimental groups.4 Furthermore, those authors’ own conclusion was that the caries-preventive effect was a result of the mechanical action of chewing rather than on the different sugar substitutes.4 The wide acceptance of non-RCT is also problematic in terms of external validity because some of the trials were performed in developing countries which have high caries prevalence and a very sugar-rich diet. Another study displayed an attrition rate of more than 50%,5 which is highly compromising. It should also be emphasised that all comparisons were computed against “no chewing” groups instead of placebo control. Therefore, it is possible that the PF presented in this review represents a best-case scenario and somewhat overestimates the true caries preventive effect. It was also of interest to find that this review was initiated by the industry and that only four out of the 19 papers were published after year 2000.

An intriguing issue in this field to date has been whether the caries-preventive effect of sugar-free chewing gums can be ascribed to the various polyols themselves or to the general effect of saliva stimulation. The present paper cannot provide an answer to that. Furthermore, health-economic evaluations of preventive programs with chewing-gums are still lacking, so the question remains over whether this is a cost-effective public health measure, especially in the light of obstacles to achieve professional acceptance and patient compliance.6 The present review identifies some important gaps in our knowledge, such as the optimal dose and relative efficacy of the different polyols commonly used in chewing gums, which illustrates the need for further well-designed studies. In any case, the conclusions of this systematic review should be limited to the primary and young permanent dentition: all the included studies were performed in school-aged children.

Practice points
* There is good evidence to support the use of sugar-free chewing gums as a caries-preventive measure in schoolchildren, especially in those with increased caries risk.
* Chewing gums should be an adjunct to multiple preventive measures such as fluoride exposure, fissure sealants and patient empowerment.

1. Lingström P, Holm AK, Mejàre I, et al. Dietary factors in the prevention of dental caries: a systematic review. Acta Odontol Scand 2003; 61: 331–340.
2. van Loveren C. Sugar alcohols: what is the evidence for caries-preventive and caries-therapeutic effects? Caries Res 2004; 38: 286–293.
3. Mickenautsch S, Leal SC, Yengopal V, Bezerra AC, Cruvinel V. Sugar-free chewing gum and dental caries: a systematic review. J Appl Oral Sci 2007; 15: 83–88.
4. Machiulskiene V, Nyvad B, Baelum V. Caries preventive effect of sugar-substituted chewing gum. Community Dent Oral Epidemiol 2001; 29: 278–288.
5. Kandelman D, Gagnon G. A 24-month clinical study of the incidence and progression of dental caries in relation to consumption of chewing gum containing xylitol in school preventive programs. J Dent Res 1990; 69: 1771–1775.
6. Milgrom P, Rothen M, Milgrom L. Developing public health interventions with xylitol for the US and US-associated territories and states. Suom Hammaslaakarilehti 2006; 13: 2–11.

Author’s affiliation:
epartment of Cariology and Endodontics, Faculty of Health Sciences, University of Copenhagen, Denmark

March, 2009|Oral Cancer News|

Significant oral cancer risk associated with low socioeconomic status

Author: Saman Warnakulasuriya

Searches were made for studies in Medline, Medline In-Process and other Non-indexed Citations Embase, CINAHL, PsychINFO, CAB Abstracts 1973–date, EBM Reviews, ACP Journal Club, Cochrane Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Management Information Consortium database and Pubmed. Un-published data were also received from the International Head and Neck Cancer Epidemiology Consortium.
Study selection

Studies were identified independently by two reviewers and were included if their subject was oral and/ or oropharyngeal cancer; they used case–control methodology; gave data regarding socioeconomic status (SES; eg, educational attainment, occupational social classification or income) for both cases and controls; and the odds ratio (OR) for any SES measure was presented or could be calculated. Corresponding authors were contacted where there was an indication that data on oral and/ or oropharyngeal cancers could potentially be obtained from the wider cancer definition or grouping presented in the article, or if SES data were collected but had not been presented in the article. Methodological assessment of selected studies was undertaken.

Data extraction and synthesis
Countries where the study was undertaken were classified according to level of development and income as defined by the World Bank. Where available the adjusted OR (or crude OR) with corresponding 95% confidence intervals (CI) were extracted, or were calculated for low compared with high SES categories. Meta-analyses were performed on the following subgroups: SES measure, age, sex, global region, development level, time-period and lifestyle factor adjustments. Sensitivity analyses were conducted based on study methodological issues. Publication bias was assessed using a funnel plot.

Forty-one studies met the inclusion criteria and yielded 15 344 cases and 33 852 controls. Compared with individuals who were in high SES strata, the pooled OR for the risk of developing oral cancer were 1.85 (95% CI, 1.60–2.15; N=37 studies) for individuals with low educational attainment versus 1.84 (95% CI, 1.47–2.31; N=14) for those with low occupational social class versus and 2.41 (95% CI, 1.59–3.65; N=5) for people with low incomes. Subgroup analyses showed that low SES was significantly associated with increased oral cancer risk in high- and lower-income countries, across the world, and remained when adjusting for potential behavioural confounders.

Oral cancer risk associated with low SES is significant and related to lifestyle risk factors.

Major risk factors for oral cancer include tobacco, alcohol misuse and chewing areca nut (betel quid). Increased consumption of fruits and vegetables reduces oral cancer risk whereas human papillomavirus infection may contribute to an increased risk. Until recently the independent role of socioeconomic inequalities had not been investigated in detail. This systematic review examines whether oral cancer risk is associated with low SES.

The systematic review is well designed and sets out a clear focused question. Forty-one case–control studies were included in this meta-analysis: 24 of these were from high-income countries and 17 were from low-income countries. Three different measures were employed to define socioeconomic status: low income, low occupational social class and low educational attainment. By using all three measures in the inclusion criteria the authors accounted for the variations in SES measurements encountered in different studies reported in the literature.

It is interesting that, individually, each of the SES measures showed slightly different magnitudes of oral cancer risks, with OR ranging from 1.84–2.42. More studies (N=7) had used educational attainment as a measure, but the most significant risk of oral cancer was associated with low income.

Notably, four out of the 37 studies that provided data on the association of education with oral cancer risk concluded that high educational levels were associated with an increased risk for oral cancer. The authors provided some study characteristics (Table 2) and it can be seen these four studies were typical of other studies although some had rather small case numbers. There is evidence that among groups of young people affected by oral cancer (compared with older people) there is over-representation of subjects in high occupational social classes.1

Regular consumption of fruits and vegetables tends to be more rare in people with low incomes. The authors’ subgroup analysis did not include information on any adjustment for nutrition which could have a significant effect on these estimates.2

The authors note the limited uniformity of data presentation in many of the reported studies. There were huge inter-study variations in classifying subjects. For example, in lower income countries, “no education” was compared with “ever education”, whereas in high-income countries “high school education” was compared with “university education”. This highlights an important issue when variables describing SES are allocated in study protocols. SES data gathering should be carefully planned to allow useful conclusions to be drawn from demographic studies.

In addition to major risk factors for oral cancer (tobacco, alcohol and betel quid use), SES is also an important determinant of risk. This meta-analysis provides robust evidence that SES is an independent risk factor following adjustments for potential behavioural confounders. We could therefore speculate that the macro environment associated with low SES, such as the effect of poor education on health, lack of access to healthcare, hygiene, poor nutrition, unfavourable working environment and poor living conditions may contribute to causation of oral cancer by complex interactions in society, in synergy with the other known risk behaviours often encountered in any low SES groups.

This meta-analysis does make a significant contribution to the oral cancer literature in that it identifies low SES as an independent variable associated with an increased cancer risk. In addition to its utility for healthcare agencies interested in the control of oral cancer, this meta-analysis provides useful data for the global partnerships and agencies that aim to reduce the poverty gap, and will help drive the case for better targeted and prioritised research to address the health needs of poor populations.

1. Llewellyn CD, Linklater K, Bell J, Johnson NW, Warnakulasuriya S. An analysis of risk factors for oral cancer in young people: a case–control study. Oral Oncol 2004; 40: 304–313 | Article | PubMed | ISI |
2. Warnakulasuriya S. Food, nutrition and oral cancer. In Food Constituents and Oral Health. Edited by M Wilson. Cambridge: Woodhead; 2009: pp273–295.

March, 2009|Oral Cancer News|

Treatment approach using radiofrequency waves heats up

Author: Carmen Phillips

It began with chemotherapy-induced sleeplessness and some pie pans. At one point hot dogs were involved. It inspired residents of two small communities 1,300 miles apart, and eventually landed in the labs of two major academic medical centers. And, sadly, just 5 weeks ago, the man who began it all died of treatment complications after a nearly 7-year battle with B-cell leukemia.

The story of retired radio engineer and executive John Kanzius and the radiofrequency (RF) generator that he dreamed would one day be part of a highly effective cancer treatment captivated readers of Discover magazine and viewers of “60 Minutes.” Now his invention is maneuvering through the steps needed to demonstrate readiness for clinical testing in humans.

“Realistically, we still have hoops to jump through and things to prove,” said Dr. Steven A. Curley from the University of Texas M.D. Anderson Cancer Center, who, along with Dr. David Geller from the University of Pittsburgh Medical Center, has been part of this project since its earliest days. “But I’ll continue to work on this and move it forward because I think it has great promise.”

An image of pancreatic cancer cells treated with gold nanoparticles.
The cells on the left received 2 minutes of external radiofrequency (RF)
field treatment resulting in unstable nuclei and intracellular damage.
The cells on the right received no RF treatment and their nuclei and
organelles remain intact.  (Image courtesy of Dr. Stephen Curley)

A Trojan Horse…on Fire
RF, Mr. Kanzius realized one restless night, is an ideal way to attack cancer cells from outside the body. At low levels, it doesn’t harm healthy tissue, but in a matter of minutes it can heat up metal in the RF field to nearly 130 degrees Fahrenheit. So, figured Mr. Kanzius, why not use RF waves to heat up metal nanoparticles that have found their way into cancer cells?

At his summer home in Sanibel, FL, he used pie pans to create his first RF device. In the garage of his long-time home in Erie, PA, Mr. Kanzius tested the device on America’s favorite ballpark snack. He would eventually use his own money to build a more sophisticated RF generator that Dr. Geller, and later Dr. Curley, went on to use in cancer cell line and animal model studies.

In these studies, nanoparticles are introduced and exposed to low-level RF waves for just a few minutes. The intense heat generated in the infiltrated cells “denatures proteins, disrupts lipid bilayers, and results in irreparable damage to intracellular structures and organelles,” Dr. Curley and his colleagues at M.D. Anderson explained in their most recent paper.

While the preclinical work has proven successful, there is still much to be done, stressed Dr. Geller.

“It’s one thing to kill cancer cells in a test tube, or even an animal,” he said. “It’s another to kill a tumor in a human and make a cancer disappear.”

Reaching the Target
The work completed thus far demonstrates the rapid progression from a concept of blistering malignant cells with RF waves toward precisely focusing RF waves on cancer cells by using nanoparticles with targeting agents attached to them. The initial work by Dr. Curley’s team involved single-walled carbon nanotubes unadorned by a targeting molecule, given to Dr. Curley by a patient he was treating at the time—Dr. Richard Smalley, a Nobel Prize winner for nanotechnology research who died in 2005.

Both Dr. Curley’s and Dr. Geller’s groups are now using gold spherical nanoparticles. In their most recently published work, Dr. Curley’s group attached the EGFR-targeted monoclonal antibody cetuximab (Erbitux) to the gold nanoparticles.

Introducing these gold nanoparticles into cell lines of pancreatic and colorectal cancer, which both overexpress EGFR, and exposing them for just a minute to an RF field killed nearly 100 percent of the cancer cells, the M.D. Anderson team reported.

“We probably wouldn’t use cetuximab in humans,” Dr. Curley noted. “EGFR is highly expressed in many normal tissues, and we would get significant uptake in normal tissue in the RF field.”

Dr. Geller’s team has shown that they can use RF to heat up liver tumors in a rat model. They used “naked” gold nanoparticles in the experiments, however, that were injected directly into the tumors. Both Drs. Curley and Geller are still working to find molecules that are highly specific to cancer cells.

“For each cancer, we’re going to have to come up with unique strategies,” Dr. Geller explained. “What works for liver cancer may not work for breast or prostate cancer.”

The Path Forward
Tackling cancer in this way, said Dr. Piotr Grodzinski, program director for the NCI Alliance for Nanotechnology in Cancer, is “generally an attractive idea.” Other researchers, in fact, have developed similar approaches, he added, “with their own twists.”

Texas-based Nanospectra Biosciences, for example, has received FDA approval for a phase I study in patients with unresectable head and neck cancer using a device that emits near-infrared light to heat up gold nanoparticles in tumors. And the German company MagForce developed a device that employs an alternating magnetic field to heat up magnetized nanoparticles; the device is being tested in phase I and II trials in Europe for several cancers.

Other investigators, added Dr. Nicholas Panaro, a senior scientist in NCI’s Nanotechnology Characterization Laboratory, are studying different targeting molecules—DNA fragments called aptamers, and diabodies, which are antibody fragments—to see if they can more effectively deliver nanoparticles only to cancer cells.

Meanwhile, Therm Med, the company established by Mr. Kanzius to help commercialize his device, is in the process of scaling it up so that it can be used for large animal and eventually human studies. Drs. Geller and Curley believe that with continued progress and funding they can launch initial human trials in the next few years.

“John was a one of a kind,” said Dr. Geller. “We certainly hope to continue the research because that’s what he wanted us to do.”

March, 2009|Oral Cancer News|

Colleen Zenk Pinter’s battle with cancer

Author: By Colleen Zenk Pinter, as told to Micki Siegel

The cameras were rolling and I was trying to say my lines, but I knew I sounded like I’d had a stroke. For the last 30 years I’ve been playing Barbara Ryan, a feisty woman who’s never at a loss for words, on As the World Turns. But now I couldn’t get the words out clearly.

Viewers started writing to the show and flooding fan websites, wondering why I sounded so awful. I knew I owed them an explanation, but I just wasn’t ready. I was still digesting the bad news.

On March 5, 2007–my daughter Georgia’s 14th birthday–I found out that I had oral cancer. Stage 2 squamous cell carcinoma, to be exact. I remember leaving the doctor’s office, picking up Georgia’s birthday cake, wrapping some presents and hosting a party as if nothing had happened. I was in shock.

I thought most people who got oral cancer were men who smoked and drank heavily, and I don’t fall into any of those categories. But I learned that I was probably among the fastest-growing group of oral cancer patients, because my illness was most likely caused by HPV-16, a strain of a common sexually transmitted virus that can also cause cervical cancer.

Scary Signs
It started in December 2005, when I noticed that my speech was changing. Suddenly my s’s had a bit of a whistle. My dentist said that because I was in my 50s, my teeth were shifting. Then, in July 2006, I developed a cold sore on my tongue. It went away and came back a few times, but by the end of the year it just stayed there, getting bigger and bigger.

I finally saw an oral surgeon in January 2007; by then, the sore was painful, raw and red, and ugly. The surgeon thought it was a combination of a fungal and a bacterial infection. He even said, “I’ve never seen a cancer that looked like that, so I’m sure that’s not what we’re dealing with.” That was the first time cancer even crossed my mind.

He prescribed a special mouthwash, which made it shrink for a little while. But after six weeks it stopped working. I went back to his office, and that’s when he found a tumor underneath the infection and biopsied it.

I had a follow-up appointment with the surgeon on a Monday. He told me it was cancer. I broke the news to my mother and my husband [actor Mark Pinter], who was in California working on a project. But I didn’t cry–there was no time for that. I went right to my computer to Google everything I could about my diagnosis. Meanwhile, I planned to see at least two specialists in the next few days.

Saving My Speech
My daughter, Kelsey, took me to the first doctor. He told me I needed a partial glossectomy (removal of part of the tongue), as well as a radical neck dissection: The doctor would start at my ear and cut all the way across my throat. He’d remove all the lymph nodes and surrounding tissues, and I’d probably be left with a huge pouch where a skinny neck should be. And a scar. As an actress, all I could think about was how terrible I would look.

When I got home that night, I had a message from my oral surgeon saying that he had been able to get me an appointment with another head and neck cancer specialist, Dr. Clarence Sasaki at Yale–New Haven Hospital.

Mark came home from California, my mom came in from Florida, and we went to Yale to meet Dr. Sasaki. He examined me, then asked me to wait down the hall while he presented my case to a group of doctors called the Tumor Board. Finally, Mark and I were ushered into a room with about 20 doctors. It was like walking into the audition of my life.

The board’s conclusion: Since the cancer was only in my tongue, I’d get a partial glossectomy with reconstruction so my speech would be affected as little as possible. Dr. Sasaki said they would take the right half of my tongue and all the muscle structure underneath. And then they would reconstruct my tongue by cut-ting a flap from the left side and bringing it around to replace the part of my tongue that had been removed. I was so relieved that I didn’t have to have my neck sliced open.

The operation went well, and first thing the following morning, Mark woke me and announced: “The eggs hatched!” (I have several birds as pets, and at that time one of them was a pregnant canary.) I ran down-stairs to the nest and saw this little thing with its mouth wide open. I stood there and watched as two other eggs were hatched. To me this was a sign of rebirth–a sign that I was going to be just fine.

Work Imitates Life
Unfortunately, my treatment wasn’t quite finished. When the pathology report came back, the board decided that I needed radiation. I had brachy-therapy, a process in which 20 minuscule radioactive rods were implanted in my tongue. Afterward, I was in unbelievable pain. Even worse, a few days later my tongue “rejected” many of the rods. That meant I would need another procedure to have them put back in.

I was despondent. I was already in so much pain. Before going back to the hospital, I spent a few days at the studio filming as many scenes as I could. My speech was a little slurred, but the show didn’t address it right then.

When I got to the operating room, I knew I was in trouble when the doctor said, “I am so sorry I have to do this to you.” They put me on a table and strapped me down, since they couldn’t give me any more anesthesia. This was my third major surgery in just six weeks. I’d given birth naturally three times–and this was the worst thing I’d ever felt in my life. Happily, though, this time the radiation rods stayed in place, and in October 2007 I was declared cancer-free.

I was anxious to get back to work, but I also had a new mission: to warn everyone about this disease. Since I’d been on As the World Turns for so long, the writers and producers agreed to “diagnose” my character with oral cancer in early 2008 and weave it in as a storyline.

Still Fighting
Although my doctors said I was healthy, I was always looking over my shoulder. Oral cancer has a very high recurrence rate, and within a year I fell into the unlucky group. The day after Thanksgiving 2008, I went back for further surgery to remove an enlarged lymph node along my jawline. I was scared to death. I ended up having a modified neck dissection–the doctors cut from just below my right ear to halfway across my neck (they stopped at the chin) and removed the lymph nodes.

The good news: 21 of the nodes tested negative. But one was so full of cancer it essentially exploded and was growing into the neck muscle wall. There’s no way of knowing where else the cancer cells might have landed, so I’m in for four and a half weeks of radiation. I haven’t started the radiation as I write this, but doctors tell me there will be severe side effects. I already have a pouchy neck and a 6-inch scar across it.

I don’t know what my future will be, but I hope to get healthy and go back to work soon. Despite the change in my appearance, I know I’ll always be welcome on As the World Turns–the cast is like my family.

The irony is that my cancer could have been found and treated so easily long before it progressed. My doctors say the tumor had been growing for two and a half to four years before we found it. I beg everyone who’s reading this, please, go to your dentist and ask for an oral cancer exam. It takes less than five minutes, and it could save your life.

March, 2009|Oral Cancer News|

A fighting partner

Source: RDH Magazine
Author: Donna Marie Grzegorek

Dentists and hygienists should be teaming up to be the first line of defense against oral cancer.

In the United States this year, more than 35,310 new cases of oral and pharyngeal cancer will be diagnosed, with an estimated 7,590 people who will die. Sadly, survival rates for oral cancer have not changed significantly in 40 years, and embarrassingly, dental professionals are alone among health professionals who screen for cancer with their hands and eyes. Under the watchful eye of the dental practitioner, 70% of the lesions found during visual and palpation exams are detected in Stage III and Stage IV, and one–half of those patients (58%) will survive less than five years. It gets worse … a survey conducted by the American Dental Association revealed that only 15% of patients reported having an oral cancer examination during a routine dental appointment. And noteworthy, failure to diagnose oral cancer is the number two cause of dental malpractice in the United States. Oral cancer claims constitute the most expensive malpractice suits and the most difficult to defend, with awards typically exceeding $1 million.

If these statistics are not compelling enough, take note that the face of oral cancer is changing. No longer should we look at the older male patient with a chronic history of tobacco and alcohol abuse as the only high–risk patient. Twenty–seven percent of all new oral cancers are occurring in young adults with no associated risk factors. So I ask you … isn’t it time to increase the “standard of care” and incorporate a comprehensive early oral cancer detection program into your office protocol?

Where to begin
I strongly feel that the dental hygienist should be the first line of defense against this insidious disease. The practice act in many states limits the hygienist’s ability to diagnose. Therefore, an early oral cancer detection protocol must involve a partnership between the dental hygienist and the dentist.

Several years ago, upon approaching my employer and stating my desire to increase the standard of care we provide to our patients regarding early oral cancer detection, we initiated our program. We discussed the benefits of incorporating an adjunctive blue spectrum light screening technology into our examination. Two weeks later, upon formulating an appropriate protocol, we launched our enhanced oral cancer screening program.

We began our new effort by educating our patient base. The preponderance of the hygiene appointment was dedicated to discussing the risks of oral cancer, reviewing statistics, and performing the visual, palpation, and blue light examination.

It is critical that the patient understand an adjunctive screening device is not a definitive diagnostic device, but rather a means of detecting disease early, in asymptomatic people.

Positive results are not diagnostic. They are a way to identify persons at increased risk for the presence of cancer, which warrants further evaluation. I review medical/dental and lifestyle risks that each patient possesses. This includes conversations regarding HPV and oral sex.

HPV and oral cancer
Human papillomavirus is now recognized to play a role in the pathogenesis of a subset of head and neck squamous cell carcinomas (HNSCCs), particularly those that arise from the lingual and palatine tonsils within the oropharynx. HPV cancers are the fastest growing segment of the oral cancer population. Although there are more than 100 different types of HPV identified, HPV 16, 18, 31, and 45 are sexually transmitted.

According to the U.S. Department of Health and Human Services, HPV is transmitted through skin to skin contact. HPV 16 and 18 are implicated in most cervical cancers and are also responsible for anal and penile cancers. It appears that HPV 16 is identified in the overwhelming majority of HPV positive oral tumors.

It is encouraging to note that HPV positive oral cancers have significantly better survival outcomes than the non–HPV–related tumors. It is believed that the HPV–related tumors are more susceptible and vulnerable to radiation treatments than their tobacco and alcohol counterparts. It has recently become understood that HPV affects the cell’s molecular machinery. It interferes with the function of a key gene that would normally cause cells with potentially cancerous mutations to self–destruct.
Given the decline of tobacco use over the past 10 years and the increasing rate of HPV–related oral cancer, much of the blame is cast toward HPV transmission through oral sex. I make it perfectly clear to my patients that “oral sex is not safe sex.”

Foundation takes strong position
The Oral Cancer Foundation has expressed very strongly its position about non–tobacco–related oral cancers. The foundation states: “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, it is not possible to definitively know who is at risk for development of the disease, and who is not. 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 the survival rates are the highest.”
Wow ? need I say more?

Every patient should be screened
As clinicians we must remember that patients don’t walk into the office carrying a sign that states they are at high risk for oral cancer. Oftentimes patients are not truthful with the information they provide on their medical/dental histories.

With hard statistics showing that 27% of all oral cancers occur in young adults ages 18 to 35 who don’t drink and don’t smoke, what parameters can we establish to safely screen our patients? The truth is that EVERY patient should be screened for oral cancer.

I perform a comprehensive oral cancer examination during the hygiene visit on each patient age 17 and older at every recare appointment. An identical examination is repeated by the dentist when he completes his portion of the patient examination.

We believe that having two sets of eyes looking for oral cancer is better than one. This protocol has been well received by our patients. It creates value for the procedure, but most importantly it sends a message of great significance to our patients. We encourage patients to return for a complimentary re-examination if they find any oral lesion that does not resolve in two weeks.
I dispense to each patient a “self examination” visual and palpation instruction sheet. I encourage self–examination of the head and neck on a monthly basis and compare the process to breast self–examination.

Up your game
I assert that any adjunctive screening device will enhance the office “standard of care,” and improve patient health outcomes. Complete your research and choose the methodology that provides the best fit for you, your patients, and your practice. I recommend not offering the oral cancer examination as if it were an option. Present a compelling argument through education and discussion so the patient thanks you for being one of the few offices that offer such a valuable service.

I believe dental hygienists must partner with their supervising dentists to create an effective early detection protocol. The dental professional is the first line of defense against this menacing disease. Together we can make a difference. In the past 29 years, I have observed the profession of dental hygiene mature from one of mechanical tooth debridement to one of veritable health–care provider. We have a unique opportunity and a critical responsibility to counsel our patients on the importance of living healthier lives through meticulous oral health care. It’s wonderful to save a tooth, but as dental health–care providers in 2009, we have many opportunities to save lives.