Association between p53 and Human Papillomavirus in Head and Neck Cancer Survival

3/9/2008 Iowa City, IA EM Smith et al. Cancer Epidemiol. Biomarkers Prev. February 1, 2008; 17(2) 421-7 Background: High-risk human papillomavirus (HPV-HR) is a significant risk factor for head and neck cancer (HNC), abrogating normal p53 function. In addition, HPV and p53 have been associated with prognosis of these tumors but the findings have been inconsistent. We examined p53 expression and HPV-HR individually and jointly for differences in predicting HNC survival. Methods: HNC patients (n = 294) were evaluated for p53 by immunohistochemical staining. HPV was detected by PCR/dot blot hybridization and sequencing. Results: HNC tumors showed 48% with p53 overexpression and 27% with HPV-HR. Multivariate analyses showed that p53 positivity was significantly associated with higher risk of disease-specific [hazard ratio (HR); 2.0; 95% confidence interval (95% CI), 1.1-3.7] and recurrence-free mortality (HR, 2.8; 95% CI, 1.4-5.3). HPV- cases had significantly worse disease-specific survival (HR, 2.8; 95% CI, 1.3-6.3) compared with HPV-HR cases. When analyzed jointly, with p53(-)/HPV-HR tumors as the reference group, p53(+)/HPV(-) patients had the worst disease-specific (HR, 5.3; 58% versus 15%, P = 0.006) and recurrence-free survival rates (HR, 9.5; 17% versus 89%, P = 0.001), in contrast to the p53(-)/HPV(-) and p53(+)/HPV-HR groups, which had less elevated and different risks for disease-specific survival (HR, 2.5 and 1.7, respectively) and recurrence-free survival (HR, 4.2 and 7.2, respectively). Conclusion: Joint assessment of p53/HPV status provides different HRs for each clinical outcome in the four biomarker groups that are distinct from the individual biomarkers. These findings suggest that joint [...]

2009-04-16T12:24:44-07:00March, 2008|Archive|

Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial

3/9/2008 web-based article C Fakhry et al. J Natl Cancer Inst, February 20, 2008 Background: The improved prognosis for patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) relative to HPV-negative HNSCC observed in retrospective analyses remains to be confirmed in a prospective clinical trial. Method: We prospectively evaluated the association of tumor HPV status with therapeutic response and survival among 96 patients with stage III or IV HNSCC of the oropharynx or larynx who participated in an Eastern Cooperative Oncology Group (ECOG) phase II trial and who received two cycles of induction chemotherapy with intravenous paclitaxel and carboplatin followed by concomitant weekly intravenous paclitaxel and standard fractionation radiation therapy. The presence or absence of HPV oncogenic types in tumors was determined by multiplex polymerase chain reaction (PCR) and in situ hybridization. Two-year overall and progression-free survival for HPV-positive and HPV-negative patients were estimated by Kaplan-Meier analysis. The relative hazard of mortality and progression for HPV-positive vs HPV-negative patients after adjustment for age, ECOG performance status, stage, and other covariables was estimated by use of a multivariable Cox proportional hazards model. All statistical tests were two-sided. Results: Genomic DNA of oncogenic HPV types 16, 33, or 35 was located within tumor cell nuclei of 40% (95% confidence interval [CI] = 30% to 50%) of patients with HNSCC of the oropharynx or larynx by in situ hybridization and PCR. Compared with patients with HPV-negative tumors, patients with HPV-positive tumors had higher response rates after induction chemotherapy (82% vs [...]

2009-04-16T12:22:49-07:00March, 2008|Archive|

The vitamin D miracle – Is it for real?

3/9/2008 Toronto, Ontario, Canada Martin Middlestaedt GlobeandMail.com In the summer of 1974, brothers Frank and Cedric Garland had a heretical brainwave. The young epidemiologists were watching a presentation on death rates from cancer county by county across the United States. As they sat in a lecture hall at Johns Hopkins University in Baltimore looking at the colour-coded cancer maps, they noticed a striking pattern, with the map for colon cancer the most pronounced. Counties with high death rates were red; those with low rates were blue. Oddly, the nation was almost neatly divided in half, red in the north and blue in the south. Why, they wondered, was the risk of dying from cancer greater in bucolic Maine than in highly polluted Southern California? The two had arrived at Johns Hopkins a few days earlier, having driven their Mustang from their hometown of San Diego. Frank was about to begin graduate studies and Cedric his first job as a professor. It was July, and the trip through the sunny South gave them an idea as they studied the cancer maps: Exposure to sunshine varies dramatically depending on the latitude. What if that's what was behind the varying cancer rates? Their hypothesis, painstakingly developed and published six years later in the International Journal of Epidemiology, was that sunlight has a powerful anti-cancer effect through its role in producing vitamin D in bare skin. Those living at northern latitudes, they theorized, receive less sunlight and make less of the vitamin, which in [...]

2009-04-16T12:22:23-07:00March, 2008|Archive|

Timetable to beat a virus

3/6/2008 Sidney, Australia Fran Molloy Sidney Morning Herald (www.smh.com.au) In secondary schools across Australia, teenage girls are wincing their way towards the front line of the battle against cancer. A new school year means a new round of vaccinations in a program that many researchers believe has the potential to wipe out cervical cancer within two generations. The vaccine targets four sub-types of the human papillomavirus (HPV), which is the most common sexually transmitted disease. Two of these sub-types are responsible for about 70 per cent of all cervical cancer. Girls in their first year of high school will get three jabs under a national immunisation program now in its second year. Until June next year, schoolgirls up to year 12 and women up to the age of 26 will also receive free immunisation under a catch-up program that began last April. Cervical cancer is the second most common cancer in women worldwide - after breast cancer - and is the leading cause of cancer-related death among women in developing nations, with an estimated half a million women diagnosed each year. "Eventually, we hope that this disease will be eliminated," says Professor Jim Bishop, chief executive of the Cancer Institute of NSW. "In places such as equatorial Africa, this is a major cancer in women. The vaccines may reduce the terrible situation with cervical cancer in the developing world where women present late and very often die. "There, [the situation with] cervical cancer is quite different [to] this country where [...]

2009-04-16T12:21:50-07:00March, 2008|Archive|

Targeting Tumors

3/5/2008 Moline, IL staff WQAD.com A breakthrough in radiation treatment is giving doctors a new, more accurate way to attack tumors. It uses four-dimensional imaging to zero-in on cancer. In this church sanctuary, Ken Sanders finds peace. A respite from his two year battle with throat cancer. "It makes me feel wonderful, it's the saving grace, I guess." Every day, Ken gets I-G-R-T -- image guided radiation therapy. The new four-dimensional imaging system is designed to target tumors, compensate for their motion, and miss healthy tissue around them, making it much more precise than traditional radiation. "It was as if you were hit by a shot gun, and now it's as if we have a laser-guided painting gun. We can paint the dose into a very specific target and miss the normal tissue" says Morris Geffen, MD. And because tumors move... before every treatment, the 4-D scan updates the location of the tumor, then the radiation can be realigned to hit the target. Dr. Geffen says "not only is the precision better but we're now able to escalate the dose to such a degree that we can cure more cancers. One of the more famous radiation oncologists in the world paraphrased that this is the most significant advance in cancer management in the last 25 years." "Oh it absolutely saved my life." M'liss Mahn had an inoperable tumor behind her eye "and the tumor was sitting, growing into my skull." Over 70 days of I-G-R-T, doctors targeted her tumor with [...]

2009-04-16T12:21:23-07:00March, 2008|Archive|

Smoking and human papillomavirus infection

3/4/2008 web-based article Salvatore Vaccarella et al. International Journal of Epidemiology, doi:10.1093 Background: Smoking increases the risk of squamous-cell carcinoma of the cervix, but it is not clear whether smoking increases the risk of acquisition or persistence of human papillomavirus (HPV) infection. Methods: Information on smoking was collected from 10 areas in four continents among population-based, age-stratified random samples of women aged 15 years or older. HPV testing was performed using PCR-based enzyme immunoassay. Unconditional logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) of being HPV-positive by smoking habits, adjusted for age and lifetime number of sexual partners. Results: Ten thousand five hundred and seventy-seven women (mean age 41.4 years) were included. Among current smokers, the risk of being HPV-positive increased with smoking intensity, after allowing for lifetime number of sexual partners: ORs for <5, 5–14 and 15 cigarettes per day were 1.21 (95% CI 0.95–1.54), 1.39 (95% CI 1.04–1.87) and 2.01 (95% CI 1.32–3.08), respectively, as compared with never-smokers. The risk among former smokers (OR = 0.95, 95% CI 0.73–1.23) was similar to that among never-smokers. Analyses stratified by lifetime number of sexual partners showed a significant trend in risk only for women with one lifetime sexual partner. Conclusions: Our study suggests that current, though not former, smoking is associated with an increased prevalence of HPV, after allowance for sexual covariates. Among current smokers, HPV prevalence increased with smoking intensity, but a clear dose–response relationship was exclusively seen among women who declared [...]

2009-04-16T12:20:57-07:00March, 2008|Archive|

Screening for oral cancer in a new light

3/4/2008 Chicago, IL staff Chicago Sun-Times (www.suntimes.com) Fluorescent scan helped detect man's lesions that could have developed into cancer It might be nothing serious, but a sore in your mouth that shows no sign of healing could also be a warning sign of oral cancer, which kills more than 8,000 people a year. Often, it's not diagnosed until it's advanced because symptoms -- sore throat, white or red patches on the gums or tongue, numbness -- are easy to put off to something less serious. Last year, Grant Achatz, the acclaimed chef at Alinea, shocked the food world by announcing he had late-stage oral cancer -- which, after treatment, is in remission. About 34,000 people a year are diagnosed with oral cancer nationally. Caught early, it has a 75 percent to 80 percent five-year survival rate. But late diagnosis lowers the survival rate to just 50 percent, says Richard Price, an American Dental Association spokesman. Also, screening for oral cancer typically has largely relied on a dentist spotting or feeling something amiss. But recent advances make it easier for dentists to spot problems early. Among them: the VELscope, an instrument that was showcased at the Chicago Dental Society's recent midwinter meeting. The device emits a blue light that causes the mouth to glow. Healthy tissue glows green under that light; cancerous tissue looks brown or black. The test takes two to three minutes. Some Chicago-area dentists use another device, called Vizilite -- a glowstick that highlights abnormalities in the mouth [...]

2009-04-16T12:19:57-07:00March, 2008|Archive|

What you may not know about cervical cancer vaccine for tweens

3/3/2008 Sioux Falls, SD Karen Pallarito Argus Leader (www.argusleader.com) If you're the parent of a "tween" daughter, your family physician may have recommended vaccinating her against the human papillomavirus (HPV), a sexually transmitted disease that can cause cervical cancer. But how much do you really know about this new vaccine? "I do not think that the public understands all the potential benefits of HPV vaccination, including the protection it may offer against vulvar cancer, vaginal cancer, anal cancer, and head and neck cancers," said Dr. Jessica Kahn, associate professor of pediatrics in the Division of Adolescent Medicine at Cincinnati Children's Hospital Medical Center. The U.S. Food and Drug Administration approved the HPV vaccine, called Gardasil, in June 2006, to prevent precancerous conditions of the cervix. As a result, "vaccine marketing strategies have not focused on the potential for the vaccine to prevent other cancers, and in both men and women," Kahn explained. In addition, many people do not understand the link between HPV and other cancers that affect both sexes, such as head and neck malignancies, she added. HPV is the most common sexually transmitted infection in the United States, accounting for the majority of cases of cervical cancer. At least 50 percent of sexually active people will get HPV at some point in their lives, according to the U.S. Centers for Disease Control and Prevention. While HPV usually goes away on its own, sometimes it lingers and continues to change the cells in a woman's cervix. Without treatments, these [...]

2009-04-16T12:19:17-07:00March, 2008|Archive|

Predictors of Sustained Smoking Cessation

3/3/2008 Dallas, TX Augustson, Erik M Wanke et al. RedOrbit.com Objectives: Because US smoking rates have not declined during the past decade, there is a renewed need to identify factors associated with smoking cessation. Using a nested case-control design, we explored the association between ability to sustain cessation over an extended period and demographic, smoking, medical, and behavioral variables. Methods.: We selected a sample of 1379 sustained quitters (abstinent from smoking for at least 40 months) and 1388 relapsers (abstinent for more than 8 months before relapse) from participants in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study, a nutritional intervention study involving Finnish men aged 50 to 69 years at baseline. Contingency table and multiple regression analyses were used to evaluate potential differences between the 2 groups on baseline variables. Results: Compared with sustained quitters, relapsers were more likely to report symptoms of emotional distress and higher levels of nicotine dependence, to drink more alcohol, and to report more medical conditions. Conclusions: Factors associated with both tobacco use and comorbid conditions impact an individual's ability to maintain long- term smoking cessation. Understanding the underlying mechanisms of action and potential common pathways among these factors may help to improve smoking cessation therapies. (Am J Public Health. 2008; 98:549-555. doi:10.2105/AJPH.2005.084137) Despite significant progress in smoking prevalence reduction within the United States since the mid-1990s, in the past 15 years, rates of smoking have remained virtually unchanged.1-3 Smoking continues to be a significant public health issue with asubstantial associated cancer4 and health care burden.5 [...]

2009-04-16T12:11:18-07:00March, 2008|Archive|
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