3/13/2008 Washington, DC Will Dunham www.reuters.com There are two distinct culprits behind head and neck cancer -- the long-recognized heavy tobacco and alcohol use as well as a common sexually transmitted virus, researchers said on Tuesday. The risk factors are so dramatically different in head and neck cancer in people infected with the human papillomavirus, or HPV, that it should be considered a separate disease from cases in which patients are not infected, researchers at Johns Hopkins University in Baltimore said. Head and neck cancer includes tumors in the mouth, tongue, nose, sinuses, throat and lymph nodes in the neck. "These are completely different cancers and we need to view them as such. They just happen to occur in the same place. The risk factors didn't appear to overlap at all, and there didn't appear to be any interaction between them," Dr. Maura Gillison, a professor of oncology and epidemiology, said in a telephone interview. More than 35,000 people are diagnosed with head and neck cancer annually in the United States alone. If found early, such cancer may respond well to treatment with surgery, radiation therapy and chemotherapy. Not only are the patient populations different in HPV-positive and HPV-negative head and neck cancer, but the tumors look different under a microscope, Gillison said. People with the viral-linked cancer also tend to respond better to treatment than those not HPV-infected, she added. HPV is a common sexually transmitted virus. It is well known for causing cervical cancer and genital warts. Since [...]

3/13/2008 web-based article press release ScienceDaily.com Clinicians have been perplexed by the fact that some patients given the drug cetuximab--an immune-based therapy commonly used to treat persons diagnosed with head and neck cancer, or colon cancer--have a severe and rapid adverse reaction to the drug. Sometimes the reaction includes anaphylaxis, a life-threatening condition characterized by a drop in blood pressure, fainting, difficulty breathing, and wheezing. Now researchers funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, have discovered that specific pre-existing antibodies cause the severe reaction to the drug. This discovery in turn has enabled them to explain the unusual geographic pattern of this reaction seen among individuals in the United States. The unusual findings of this investigation appear in a report published in the March 13 edition of the New England Journal of Medicine. "These intriguing research findings not only are potentially important to physicians treating certain cancer patients, but also may have broader implications for the use of immunotherapies for other diseases," notes Anthony S. Fauci, M.D., NIAID director. NIAID grantee Thomas Platts-Mills, M.D., Ph.D., who heads the Division of Allergy and Clinical Immunology at the University of Virginia, led a research study to investigate the cause of the clinical problem with cetuximab. Their newly reported findings are of immediate importance in the care of cancer patients, says Dr. Platts-Mills. "Because of the widespread use of cetuximab in cancer treatment, it may be useful to pre-screen patients for specific [...]

3/12/2008 Chicago, IL staff medheadlines.com Patient demographics has led researchers at the Johns Hopkins Kimmel Cancer Center to identify two types of cancer associated with the head and neck and the types of people more likely to get one form of the cancer or the other. The two cancers - one HPV positive and the other HPV negative - usually involve the back of the tongue and the upper throat. HPV is the human papillomavirus, a sexually transmitted disease often associated with cervical cancer. Patients who develop HPV-positive cancers are most often young, well educated, married, and earn more than $50,000 per year. They are also more likely to have had multiple sex partners, engage in oral sex, and smoke marijuana. The patients with HPV-negative cancers are often older, smoke tobacco, use alcohol, and neglect oral hygiene. The rate of HPV-positive cancers has almost doubled in the US in the last 30 years but this form of cancer seems to respond better to treatment, leading to longer survival rates, than the HPV-negative type. Some risk factors associated with HPV-positive cancers include a history of smoking marijuana, multiple sex partners, casual sex, lack of barrier protection during oral and vaginal sex, and a history of at least one sexually transmitted disease. The risk of cancer increases with marijuana use. Study participants who smoked pot five years or longer were found to be 11 times more at risk of HPV-positive cancers of the head and neck than people who smoke nothing. Further [...]

3/12/2008 Marua Gillison MD et. al Journal of the National Cancer Institute Background: High-risk types of human papillomavirus (HPV), including HPV-16, cause a subgroup of head and neck squamous cell carcinomas (HNSCCs). We examined whether the risk factors for HPV-16–positive HNSCCs are similar to those for HPV-16–negative HNSCCs in a hospital-based case–control study. Methods: Case subjects (n = 240) diagnosed with HNSCC at the Johns Hopkins Hospital from 2000 through 2006 were stratified by tumor HPV-16 status as determined by in situ hybridization. Two control subjects (n = 322) without cancer were individually matched by age and sex to each HPV-16–positive and HPV-16–negative case subject. Data on risk behaviors were obtained by use of audio computer-assisted self-interview technology. Multivariable conditional logistic regression models were used to estimate the odds ratios (ORs) for HPV-16–positive HNSCC and HPV-16–negative HNSCC associated with risk factors. All statistical tests were two-sided. Results: HPV-16 was detected in 92 of 240 case subjects. HPV-16–positive HNSCC was independently associated with several measures of sexual behavior and exposure to marijuana but not with cumulative measures of tobacco smoking, alcohol drinking, or poor oral hygiene. Associations increased in strength with increasing number of oral sex partners (Ptrend = .01) and with increasing intensity (joints per month, Ptrend = .007), duration (in years, Ptrend = .01), and cumulative joint-years (Ptrend = .003) of marijuana use. By contrast, HPV-16–negative HNSCC was associated with measures of tobacco smoking, alcohol drinking, and poor oral hygiene but not with any measure of sexual behavior or [...]

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 [...]

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 [...]

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 [...]

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 [...]

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 [...]

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 [...]