DNA repair biomarker profiling of head and neck vancer: Ku80 rxpression predicts locoregional failure and death following radiotherapy

Source: American Association for Cancer Research Abstract Purpose: Radiotherapy plays an integral role in the treatment of head and neck squamous cell carcinoma (HNSCC). Although proteins involved in DNA repair may predict HNSCC response to radiotherapy, none has been validated in this context. We examined whether differential expression of double-strand DNA break (DSB) repair proteins in HNSCC, the chief mediators of DNA repair following irradiation, predict for treatment outcomes. Experimental Design: Archival HNSCC tumor specimens were assembled onto a tissue microarray and stained with antibodies raised against 38 biomarkers. The biomarker set was enriched for proteins involved in DSB repair, in addition to established mechanistic markers of radioresistance. Staining was correlated with treatment response and survival alongside established clinical and pathologic covariates. Results were validated in an independent intramural cohort. Results: Ku80, a key mediator of DSB repair, correlated most closely with clinical outcomes. Ku80 was overexpressed in half of all tumors, and its expression was independent of all other covariates examined. Ku80 overexpression was an independent predictor for both locoregional failure and mortality following radiotherapy. The predictive power of Ku80 overexpression was confined largely to HPV-negative HNSCC, where it conferred a nine-fold greater risk of death at two years. Conclusions: Ku80 overexpression is a common feature of HNSCC, and is a candidate DNA repair-related biomarker for radiation treatment failure and death, particularly in patients with high-risk HPV-negative disease. It is a promising, mechanistically rational biomarker to select individual HPV-negative HNSCC patients for strategies to intensify treatment. Clin Cancer Res; [...]

RoboDoc: deft mechanized hands aid Memphis surgeons in operating rooms

Source: www.commercialappeal.com Author: Tom Charlier The cancer in James Entrekin's throat has curdled around the base of his tonsils, way too far down for a traditional surgeon to reach without doing a lot of cutting and bone-breaking. But there's nothing traditional about the surgery going on in this Methodist University Hospital operating room. Employing nimble, cable-thin arms, a robot reaches into Entrekin's mouth while wielding four instruments at once -- removing tumors, cauterizing vessels, suctioning fluids and transmitting three-dimensional video images of the whole thing. In a couple of hours, it's over. And since there was no need to cut open his face and throat and break his jaw, as is done in conventional oral-cancer surgeries, Entrekin will enjoy a lower risk of complications and a much shorter recovery period, while avoiding extended difficulties swallowing and speaking. "You avoid all that because that natural anatomy is not violated," says Dr. Sandeep Samant, who guided the robot from a console in a corner of the operating room. Although there are many types of surgeries where they can't be used, robots such as the nearly $2 million device used in Entrekin's case are carrying an ever-growing workload in the operating rooms of Memphis hospitals. Less than a decade after robotic surgery was introduced in Memphis, there now are five robots -- one each in Methodist University, Methodist North and Methodist Germantown and two at Baptist Memorial Hospital-Memphis -- performing roughly 1,000 operations annually. They're doing hysterectomies, removing prostates and kidneys, [...]

Smokeless tobacco may be on its way out of Major League Baseball parks

Source: www.latimes.com Author: Karen Kaplan, Los Angeles Times Major League Baseball begins the 2011 season in two days, and if public heath officials have their way it will be the last season during which players will be able to chew and spit smokeless tobacco on the field. The leaders of 15 public health departments in cities with professional baseball teams sent a letter Monday to MLB Commissioner Bud Selig and Michael Weiner, executive director of the union representing major league players, urging them to forbid the use of smokeless tobacco products. Tobacco has been banned in baseball’s minor leagues since 1993. “The use of smokeless tobacco endangers the health of Major League ballplayers and sets a terrible example for the millions of young people who watch baseball at the ballparks and on TV,” the health chiefs wrote. The letter continues: Tobacco use is the number one cause of preventable death in the United States, killing more than400,000 people each year. As cigarette smoking has declined, the tobacco industry has increased its marketing of smokeless products and is spending record sums to promote them. But smokeless tobacco use is itself very dangerous, causing serious diseases of the mouth, including oral cancer. In addition, there is reason to worry that smokeless tobacco use by young persons may serve as a gateway to cigarette smoking, this nation’s leading preventable cause of premature death and disease. As officials in Major League cities around the country, we know that baseball is important to civic life [...]

Orofacial pain onset predicts transition to head and neck cancer

Source: ScienceDirect.com David K. Lam and Brian L. Schmidt Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, CA, USA Bluestone Center for Clinical Research, New York University, New York, NY, USA Department of Oral and Maxillofacial Surgery, New York University, New York, NY, USA Abstract Contrary to a clinical aphorism that early head and neck cancer is painless, we show that patients who develop head and neck cancer experience significant pain at the time of initial diagnosis. We compared orofacial pain sensitivity in groups of patients with normal oral mucosa, oral precancer, and newly diagnosed oral cancer. The University of California San Francisco Oral Cancer Pain Questionnaire was administered to these patients at their initial visit, before being prescribed analgesics for pain and before any treatment. In contrast to those with biopsy-proven normal oral mucosa and oral precancer, only oral cancer patients reported significant levels of spontaneous pain and functional restriction from pain. Moreover, oral cancer patients experienced significantly higher function-related, rather than spontaneous, pain qualities. These findings suggest an important predictor for the transition from oral precancer to cancer may be the onset of orofacial pain that is exacerbated during function. Screening patients who have new-onset orofacial pain may lead to a diagnosis of early resectable head and neck cancer and may improve quality of life and survival for head and neck cancer patients.

Tea, coffee and oral cancer risk

Source: Nature.com-Evidence Based Dentistry Question: Is there a relationship between coffee and tea intake and head and neck cancers? Data sources Pooled individual-level data from nine case–control studies of head and neck cancers, including 5,139 cases and 9,028 controls. Study selection Nine case-control studies were selected from the International Head and Neck Cancer Epidemiology (INHANCE) consortium pool of 33 studies, which included information on coffee (caffeinated and decaffeinated) and tea drinking and cancer of the oral cavity and pharynx. Seven studies also included information on laryngeal cancer. Data extraction and synthesis Data from individual studies were checked for inconsistencies and pooled in a standardised way into a common database, including a range of sociodemographic, behavioural, lifestyle and health information. Data on consumption across studies were then converted into cups of de/caffeinated tea or coffee per day. The association between head and neck cancers and caffeinated coffee, decaffeinated coffee or tea intake was assessed by estimating the odds ratios (OR) and the corresponding 95% confidence intervals (95% CI) using a two-stage random-effects logistic regression model with the maximum likelihood estimator. Pooled ORs were also estimated with a fixed-effects logistic regression model. In addition, a test for heterogeneity among studies was conducted. Results Caffeinated coffee intake was inversely associated with the risk of cancer of the oral cavity and pharynx: the ORs were 0.96 (95% CI, 0.94–0.98) for an increment of one cup per day and 0.61 (95% CI, 0.47–0.80) in drinkers of >4 cups per day versus non-drinkers. This latter estimate [...]

Certain parts of the brain activated in people who heard tailored health messages and quit smoking

Staff writer, Healthy and Fit Magazine. com People who demonstrated a stronger brain response to certain brain regions when receiving individually tailored smoking cessation messages were more likely to quit smoking four months later, a new study finds. The new University of Michigan study underscores the importance of delivering individually tailored public health messages to curb unhealthy behaviors, said principal investigator Hannah Faye Chua, who led the study as a research assistant professor at the U-M School of Public Health. It also begins to uncover the underlying neural reasons why these individually tailored messages are so much more effective than a one-size-fits-all approach, said Chua, who now works in the private sector. The study is scheduled for advance online publication Feb. 27 in the journal Nature Neuroscience Researchers have known for 15 years that tailored public health messages that account for a person’s individuality work better at curbing unhealthy behaviors but until now, they haven’t known why. Chua and the research team hypothesized that portions of the brain activated during self-related processing were also engaged when people received individually tailored health messages, and that this brain activity accounted for the increased effectiveness of tailored messages. For the study, the research group assessed 91 people who wanted to stop smoking, and based on those answers they designed an individual smoking cessation program for each subject. Next, researchers imaged subjects’ brains with MRI to see which portions responded to tailored and untailored messages about smoking cessation, and also to neutral messages. They [...]

Pioglitazone Shows Promise for Oral Cancer Prevention

Laird Harrison Medsscape staff writer San Diego, California — In a phase 2 clinical trial, the thiazolidinedione pioglitazone partially or completely eliminated two thirds of leukoplakia lesions, which can sometimes become cancerous, researchers reported here at the International Association of Dental Research 89th General Session and Exhibition. 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 [...]

Rise of tongue cancer in young, white females

www.medscape.com Roxanne Nelson - staff journalist for Medscape Oncology. The incidence of oral tongue squamous cell carcinoma has been rising in young white American women, according to a new report. For the past 3 decades, the incidence has been increasing in white men and white women 18 to 44 years of age, but the trend is most pronounced in young white women. In a report published online March 7 in the Journal of Clinical Oncology, the authors found that the incidence of oral cavity squamous cell carcinoma was declining for all age groups. The incidence of oral cavity and tongue cancer also was decreasing for nonwhite individuals. However, among people 18 to 44 years of age, the incidence of oral tongue cancer climbed 28% between 1975 and 2007. Among white people in this age group, the incidence increased 67%. The rising rates were most dramatic for white women, with a jump of 111%. "Lately, we have been seeing more oral tongue cancer in young white women in our clinic. So we looked at the literature, which reported an increase in oral tongue squamous cell carcinoma in young white individuals, but couldn't find any information about gender-specific incidence rates, so we decided we should take a look at the SEER [Surveillance, Epidemiology, and End Results] data," said lead author Bhisham Chera, MD, assistant professor in the Department of Radiation Oncology at the University of North Carolina School of Medicine, Chapel Hill. The authors note that historically, cancer of the oral cavity was considered to be associated with older men with histories of significant tobacco and [...]

Oral cancer screenings: dental professionals can save lives

Source: www.dentistryiq.com Author: Michelle Kratt I am sure that you have heard of HPV (human papillomavirus)? Did you know that some types of HPV can cause oral cancer? Recent studies in the United States indicate that HPV is now the leading cause of head and neck cancers at 64%, even rising above smoking, tobacco chewing, and drinking alcohol. Oral cancer accounts for 2% to 4% of all cancers diagnosed annually in the United States. The number of oral cancer cases is steadily rising, and today it is showing up in younger patients. More than 37,000 Americans will be diagnosed with oral or pharyngeal cancer this year. It will cause more than 8,000 deaths, killing roughly one person per hour, 24 hours per day. Of those 37,000 newly diagnosed individuals, only slightly more than half will be alive in five years. The death rate for these types of cancer is so high not because it is hard to discover or diagnose, but because it is caught too late in its development, with 70% found in Stage III or IV. Aside from the usual risk factors — tobacco and alcohol, ultraviolet light, poor nutrition, immune system suppression, lichen planus, and history of cancer — the addition of HPV as a risk factor for oral cancer has made it extremely difficult to easily define high-risk individuals (25% of mouth cancers and 35% of throat cancers are caused by HPV). Another risk factor, although controversial, is ill-fitting dentures. It has been suggested that long-term [...]

Evaluation of human papillomavirus testing for squamous cell carcinoma of the tonsil in clinical practice

Source: jcp.bmj.com Authors: Selvam Thavaraj et al. Background: Oncogenic human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC) is a subtype of head-and-neck cancer with a distinct clinical and prognostic profile. While there are calls to undertake HPV testing for oropharyngeal SCCs within the diagnostic setting and for clinical trials, there are currently no internationally accepted standards. Methods: 142 tonsil SCCs were tested using p16 immunohistochemistry (IHC), high-risk HPV DNA in situ hybridisation (ISH) and HPV DNA polymerase chain reaction (PCR; GP5+/6+ primers). Results: There were high levels of agreement between pathologists for p16 IHC and HPV ISH scoring; however, around 10% of HPV ISH cases showed some interobserver discrepancy that was resolved by slide review. The combination of p16 IHC and HPV ISH classified 53% of the samples as HPV-positive, whereas the combination of p16 IHC and HPV PCR classified 61% of the samples as HPV-positive. By employing a three-tiered, staged algorithm (p16 IHC/HPV ISH/HPV PCR), the authors were able to classify 98% of the cases as either HPV-positive (p16 IHC+/HPV DNA+; 62%) or HPV-negative (p16 IHC−/HPV DNA−; 35%). Conclusions: The current study suggests that using a combination of p16 IHC/HPV ISH/HPV PCR, in a three-tiered, staged algorithm, in conjunction with consensus reporting of HPV ISH, leads to less equivocal molecular classification. In order to ensure consistent reporting of this emerging disease, it is increasingly important for the head-and-neck oncology community to define the minimum requirements for assigning a diagnosis of ‘HPV-related’ oropharyngeal SCC in order to inform prognosis and [...]

Go to Top