oropharyngeal cancer

NIH-funded study finds new potential drug targets by uncovering a range of molecular alterations in head and neck cancers

Source: www.nih.gov
Author: Staff
 

Investigators with The Cancer Genome Atlas (TCGA) Research Network have discovered genomic differences — with potentially important clinical implications — in head and neck cancers caused by infection with the human papillomavirus (HPV). HPV is the most common sexually transmitted virus in the United States, and the number of HPV-related head and neck cancers has been growing. Almost every sexually active person will acquire HPV at some point in their lives, according to the Centers for Disease Control and Prevention.

The researchers also uncovered new smoking-related cancer subtypes and potential new drug targets, and found numerous genomic similarities with other cancer types. Taken together, this study’s findings may provide more detailed explanations of how HPV infection and smoking play roles in head and neck cancer risk and disease development, and offer potential novel diagnostic and treatment directions.

The study is the most comprehensive examination to date of genomic alterations in head and neck cancers. The results were published online Jan. 28, 2015 in the journal Nature. TCGA is jointly supported and managed by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both parts of the National Institutes of Health.

The U.S. Food and Drug Administration-approved HPV vaccines should be able to prevent the cancers caused by HPV infection in head and neck cancers and elsewhere, including anal cancer, whose incidence has also been increasing. However, these vaccines work by preventing new infections, and the long interval between infection and cancer development make it important to understand the molecular changes that bring about these HPV-positive head and neck cancers — as well as those that lead to the HPV-negative cancers — and to develop new approaches for treating them.

“The rapid increase in HPV-related head and neck cancers, noticeably in oropharyngeal tumors, has created an even greater sense of urgency in the field,” said D. Neil Hayes, M.D., M.P.H, senior author of the study report and associate professor of medicine at the University of North Carolina (UNC) and the UNC Lineberger Cancer Center at Chapel Hill. Oropharyngeal cancer starts in the oropharynx, which is the part of the throat just behind the mouth. “We’re uncovering differences between tumors with and without HPV infection, and these new data are allowing us to rethink how we approach head and neck cancers.”

In the study, researchers performed genomic analyses on 279 tumors – head and neck squamous cell carcinomas (HNSCC) – from untreated patients. Approximately 80 percent of tumor samples were from individuals who smoked. The majority of samples were oral cavity cancers (61 percent) and larynx cancers (26 percent).

While only about 25 percent of head and neck cancers are linked to HPV infection, TCGA researchers confirmed that many patients with HPV-associated tumors have specific alterations of the gene FGFR3 and mutations in the PIK3CA gene, which are also found in a much broader set of mutations in smoking-related tumors. In contrast, while the EGFR (epidermal growth factor receptor) gene is frequently altered in HPV-negative tumors in smokers, it is rarely abnormal in HPV-positive tumors. Such insights may help in developing potential therapies and biomarkers, noted Dr. Hayes.

Head and neck cancers comprise a constellation of tumors of the mouth, throat, larynx, nasal cavity, salivary gland and elsewhere that have frequently been attributed to tobacco and alcohol use in most patients. Some 90 percent are squamous cell carcinomas, which occur in the surface layers of cells in the body. An estimated 55,000 people developed head and neck cancer in the United States in 2014. Approximately 12,000 Americans die from the diseases each year. Head and neck cancers are common worldwide, with more than 600,000 cases diagnosed each year.

“The rising worldwide incidence of head and neck cancers makes these types of large integrated genomic analyses by TCGA vital to establish a more detailed understanding of disease causes and behavior, and for the development of new treatment approaches,” said NIH Director Francis S. Collins, M.D., Ph.D.

Scientists found that more than 70 percent of head and neck cancers had alterations in genes for growth factor receptors (EGFR, FGFR, IGFR, MET, ERBB2, DDR2), signaling molecules (PIK3CA, HRAS) and cell division regulation (CCND1). These genes may play roles in pathways that control cell growth and proliferation, and for which therapies are either available or in development.

The investigators also discovered new clues about drug resistance in head and neck cancers. They found that genes affecting about 40 percent of such cancers form key parts of a pathway that helps determine cell survival and drug resistance. They showed that extra copies of the genes FADD and BIRC2, or mutations in or the absence of the CASP8gene in smoking-related cancers — all which affect the process of programmed cell death — may underlie the resistance of cancer cells to current treatments. Similarly, the absence of the TRAF3 gene, or extra copies of a gene for the growth-promoting E2F1 protein in HPV-related cancers, may also increase resistance.

The findings showed similarities between head and neck cancer genomes and other cancers, including squamous cell lung and cervical, indicating possible common paths of cancer development, and potential treatment opportunities. “It is surprising to see that head and neck tumor genomes are remarkably similar to cervical and squamous lung cancer genomes. They are from very different organs, but they show similar losses and gains of genetic material across tumors,” Dr. Hayes noted. These common genetic abnormalities belong to a pathway that protects cells from damage and stress.

“These novel findings help establish a genomic map of various head and neck cancers, provide new insights into other similar cancers and may further our understanding of how viruses can impact disease,” said NHGRI Director Eric D. Green, M.D., Ph.D.

“While many head and neck cancers are preventable, they are increasingly common throughout the world, and often challenging to effectively treat over the long term,” said NCI Director Harold Varmus, M.D. “This type of broad analysis provides important new clues for future research and treatment directions.”

The TCGA Research Network has generated data and published analyses on a number of cancers, all of which can be found on the TCGA website, http://www.cancergenome.nih.gov.

TCGA-generated data are freely available at the TCGA Data Portal and CGHub.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
March, 2015|Oral Cancer News|

HPV Related Cancers Increase in Men

Source: scientificamerican.com
Author: Robin Lloyd

A vaccine to protect against the most dangerous strains of human papillomavirus (HPV), which cause almost all cervical cancers, as well as many cases of other cancers and genital warts in both sexes, won the approval of the U.S. Food and Drug Administration nearly nine years ago. The Centers for Disease Control and Prevention now recommends that all boys and girls aged 11 or 12 receive the shots. Vaccination campaigns, aimed largely at girls and women, have fallen short of expectations. By 2013 just over half of U.S. females aged 13 to 17 had received at least one dose of either the Gardasil or Cervarix vaccine. For males, that figure was a disappointing 35 percent. Now head and neck cancers associated with the virus are on the rise, leading some experts to recommend that a gender-neutral or male-centric approach might be more effective.

HPV is the most prevalent sexually transmitted disease in the U.S. and worldwide, infecting just about all men and women at some point in their lives. Although most people clear the virus naturally, persistent infections with some strains can lead to cancer—usually cervical or oropharyngeal (affecting the back of the throat, tonsils and back of the tongue). HPV-associated cancers make up 3.3 percent of all cancer cases among women and 2 percent of all such cases among men annually in the latest available figures, yet the incidence of virally instigated oropharyngeal and anal cancers is increasing.

Ohio State University medical oncologist and epidemiologist Maura Gillison has studied men with oropharyngeal cancer in three different decades. She and other colleagues first noticed an odd shift in patient profiles in the late 1990s: younger men were showing up in her clinic, often with no significant history of smoking or heavy drinking, which are risk factors for head and neck cancers. She later found that whereas from 1984 to 1989 in the U.S. only 16 percent of oropharyngeal cancers tested positive for HPV, by 2005 that figure had skyrocketed to 73 percent. By 2020 experts project that such cancer diagnoses will exceed those for cervical cancer in the U.S., shifting the burden of HPV-associated cancers from women to men. Gillison reported these findings in October 2014 at the annual ScienceWriters meeting.

Based on these data, Gillison thinks that the female-centric approach to HPV-related cancers in the U.S. should switch to focus on both men and women. Nobel laureate Harald zur Hausen, who discovered 30 years ago that HPV causes cervical cancer, has gone further, saying that males should get the vaccine if only one sex were the focus. The vaccine is currently voluntary in most U.S. states, and only a smattering of vaccination coverage campaigns exist, such as those launched by the New York City Department of Health and the Minnesota Department of Health in the past year. Public health messages and even research literature often fail to mention male vaccination prominently or at all. Unfounded fear of vaccines and claims that the HPV shots would provoke early teen sexuality have hindered efforts to vaccinate broadly in much of the U.S.

No data exist to prove that the vaccines protect against HPV-positive oropharyngeal cancer. But such coverage is probable given that the same strains that cause most cervical, vaginal and vulval cancers also cause most head and neck cancers. If a shift in public health policy were to result in an increase in male vaccinations, experts say, at the very least rates of females’ HPV-associated cancers would decrease as a result of fewer infections acquired from men. And the rise in HPV-associated cancers in men would most likely decelerate, plateau or even reverse. A win for all of us.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
February, 2015|Oral Cancer News|

New research shows possibility of cure for HPV positive throat cancer patients

Source: Eurek Alert! The Global Source for Science News

Nice, France: Patients with cancer of the throat caused by the Human Papilloma virus (HPV+) have a better prognosis than those who are negative for the virus (HPV-). Now, for the first time, researchers have shown with convincing evidence that a group of patients with HPV+ cancer of the oropharynx (the part of the throat located behind the mouth, that makes up the region of the tonsils and the back part of the tongue where it connects to the swallowing part of the throat), can be cured in some cases even after disease has spread to distant organs in the body, like the lungs.

Dr Sophie Huang, Assistant Professor in the Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada, will tell the 5th International Conference on Innovative Approaches in Head and Neck Oncology (ICHNO) today (Friday) that her research has shown that, following intensive treatment, certain patients with HPV+ oropharyngeal cancer (OPC) and distant metastases (tumours appearing in an organ not directly related to the primary cancer site) can survive for more than two years without further evidence of disease. Such cancers are usually considered to be incurable, and the goal of treatment is usually limited to symptom control. “Our research, the largest study to date to explore survival predictors for metastatic HPV+ and HPV- oropharyngeal cancer patients, has shown that cure is a realistic goal in those patients with oligometastasis – metastases involving five or fewer lesions in one distant organ”, she will say.

Dr Huang and colleagues identified 934 patients with HPV+ OPC out of the 1238 OPC patients who had been treated at the Princess Margaret Cancer Centre between 2000 and 2011. Distant metastases were detected in 15% of these patients; 88 in the HPV+ group and 54 in those with HPV- disease. Oligometastasis was present in 24 HPV+ patients with distant metastases in a single organ.

The researchers found two types of distinct distant metastases in HPV(+) patients: “explosive” and “indolent” metastases. The explosive type metastasis, where more than ten lesions in one organ appear quickly in a short period (within three months of appearance of the first lesion), was present in 55% of the HPV+ group, as opposed to none in those who were HPV-. In both HPV+ and HPV- groups, lung was the most common metastatic site. The indolent type of metastases grow and spread at a much slower pace, most often manifesting as oligometastasis. This occurred in 24% of the HPV+ cases with metastases in a single organ as opposed to 26% of those who had HPV- cancer.

“In the HPV+ group of patients with oligometastases, when they were given definitive local treatment aimed at disease control – for example, a high radiation dose or surgical removal of the metastatic lesion, as opposed to a less aggressive treatment used to control symptoms -there was a long term disease-free period, suggesting that some may be cured,” Dr Huang will say. “In the HPV+ group with oligometases 25% were still alive after three years, whereas the percentage in the HPV- group was 15%.”

The survival advantage in HPV+ OPC patients is due to a number of factors, the researchers say. The cancer is more sensitive to radiotherapy and chemotherapy; the patients tend to be younger (an average age of 55 at diagnosis as opposed to 65) with fewer other health problems, including those caused by smoking-related illness, and this enables them to receive the more aggressive treatment necessary to eradicate metastatic disease.

The percentage of HPV positive to negative OPC cancers varies globally, depending on a number of factors, including the prevalence of smoking and the practice of oral sex. Overall the incidence of HPV+ throat cancers has increased over the past 20 years in developed countries, such as US, Canada, Japan, Australia, and some European countries. [1]

“This research has shown that metastatic HPV+ OPC patients who receive active treatment can survive considerably longer than those who did not receive treatment. One of the reasons patients with metastatic disease do not receive aggressive treatment is due to the physician and patient’s perception that this is an incurable state. We hope that these results will motivate researchers to optimise management strategies for these patients. This will not only help to produce a better quality of life and a return to work for them, but also reduce the cost to healthcare systems,” Dr Huang will say.

“We also hope that our study may trigger research to explore cost-effective methods for the early detection of metastases. Optimising and tailoring surveillance strategies for HPV+ patients are also important. For example, our research has shown that the surveillance period should be longer than the traditional two-year window, due to the possibility of later onset of metastases. Selecting the appropriate imaging method in order to detect asymptomatic oligometastasis (e.g. ultrasound for the early detection of liver metastasis) may allow salvage treatment of some patients before the cancer progresses. Finally, we hope that it will help clinicians identify patients who are best able to benefit from aggressive treatment, such as metastasectomy (surgical removal of the metastases) or stereotactic radiotherapy (highly focused high dose radiotherapy to small regions),” Dr Huang will say.

Whether it is possible to identify which patients at initial presentation are at high risk of developing distant metastasis, and which type of distant metastasis will subsequently develop are other important questions for future studies, say the researchers. “We know there is a degree of correlation between the initial stage and the risk of distant metastasis, but we did not find a strong relationship between this stage and the type of metastasis. The intensity of cigarette smoking in the years prior to the time of diagnosis is a possible factor. Being able to identify such relationships could be a huge help in deciding appropriate treatment at an early stage,” Dr Huang will say.

Although head and neck cancer is the sixth most common type of cancer worldwide, awareness of it is low, and hence the majority of diagnoses are not made until the disease is in an advanced stage, resulting in limited treatment choices and hence a reduction in the chance of survival.

Professor Jean Bourhis, co-chair of the conference scientific committee, said: This important piece of research adds substantially to what we know about the role and the importance of the Human Papilloma Virus (HPV) in oropharyngeal cancers and gives real hope of improvement in both diagnosis and treatment to those who are affected by the condition.”

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1Chaturvedi AK, Anderson WF, Lortet-Tieulent J, et al. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. Journal of Clinical Oncology : official journal of the American Society of Clinical Oncology 2013;31(36):4550-9.

Abstract no OC-044: Proffered paper session, Auditorium Athena, Friday 16.00 hrs

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

February, 2015|OCF In The News|

Study finds Oral HPV Infection Lasts Longer in Older Men

Author: Staff
Source: winnipegfreepress.com
 

FRIDAY, Jan. 9, 2015 (HealthDay News) — One type of oral HPV (human papillomavirus) infection, HPV16, seems to last a year or longer in men over the age of 45 than it does in younger men, new research indicates.

HPV16 is the form of HPV often associated with the onset of head and neck cancers (oropharyngeal), the study team noted.

“Oral HPV16 is the HPV type most commonly found in HPV-driven oropharyngeal cancers, which have been increasing in incidence recently in the United States,” said study author Christine Pierce Campbell in a American Association for Cancer Research news release. She is an assistant member in the department of Cancer Epidemiology and Center for Infection Research in Cancer at the Moffitt Cancer Center in Tampa, Fla.

“We don’t know how long oral HPV infection must persist to increase risk for head and neck cancer,” she added, “but we assume it would be similar to cervical infection, where it is generally believed that infections persisting beyond two years greatly increase the risk of developing cervical cancer.”

The study was released online on Jan. 9 in Cancer Prevention Research.

The researchers analyzed four years of samples from more than 1,600 men. The samples were collected every six months.

During the study, 23 men had two or more positive oral HPV16 samples. Of these, 10 had HPV16 when the study began.

In the group that had HPV16 at the start of the study, nine had infections that lasted a year or more. Additionally, the researchers found that eight of these infections lasted two years or more, and two lasted four years or more, the researchers found.

In those who developed infections during the study, the team found that infections in men older than 45 all lasted one year or more. By contrast, just half the infections among men 31 to 44 years persisted for one year or longer. And none of the infections detected among men 18 to 31 years lasted for a year, according to the researchers.

“Our results show that some oral HPV16 infections persist in men for four years or more and that persistence seemed to increase with age,” Pierce Campbell said.

She also noted that genital HPV infections usually clear up in two years or less. This study’s findings suggest that oral infections may be more persistent than genital HPV.

More information

For more information on oral HPV, visit the The Oral Cancer Foundation.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
January, 2015|Oral Cancer News|

Doctors Trying To Remind Americans That The HPV Vaccine Isn’t All About Sex

Source: thinkprogress.org
Author: Tara Culp-Ressler

 

Dr. Ronald A. DePinho is on a mission.

 
DePinho, who’s been a cancer researcher for decades and currently serves as the president of the University of Texas MD Anderson Cancer Center, wants to reframe the national conversation about the HPV vaccine to drive home a fundamental point.

 
“It’s important to appreciate that this is a cancer vaccine. A cancer vaccine!” DePinho said in an interview with ThinkProgress. “It’s a dream come true that we’ve converted knowledge into something that can actually save lives and avoid getting cancer in the first place. It’s really what we have been hoping for, and now we have it.”
Since the introduction of the HPV vaccine in 2006, the rate of human papillomavirus in teenage girls has plummeted. And the research in this field continues to advance. On Thursday, the Food and Drug Administration approved an updated version of the Gardasil vaccine that protects against nine strains of the cancer-causing virus — more than twice as many as the 2006 version, which covered just four strains.

 
According to DePinho, that’s a really significant advance for cancer care. He doesn’t want it to get lost in the ongoing controversy about HPV vaccination, a round of shots that some parents still worry is unsafe or inappropriate for their kids.
There’s a persistent myth, for instance, that giving teen girls the shots will spur them to become more “promiscuous” because they know they’ll be protected from a sexually transmitted infection. Large scientific studies have debunked the notion that there’s any link between the HPV vaccine and sexual activity, but inoculation rates still lag behind in some of the Southern states that are wary to provide teens with preventative tools to protect their sexual health.
In general, HPV vaccination rates in the U.S. are still much too low, hovering around 30 percent. Public health professionals are aiming to increase those rates dramatically, to at least 80 percent — closer to the percentage of people who get vaccinated against the virus in other developed countries.

 
To accomplish that, the health professionals who have dedicated their lives to treating HPV-related cancers want to move the conversation away from sexuality altogether. Instead of framing Gardasil as vaccine that protects against an STD — which might give some Americans the impression that they don’t need to worry about it — they want to present it as a vaccine that protects against cancer.

 
“It doesn’t seem like it makes sense to see it in terms of a vaccine for a sexually transmitted disease necessarily,” Dr. Erich Sturgis, an expert in head and throat cancer who works as the program director for the MD Anderson Oropharynx Program, said in an interview with ThinkProgress. “Most of us will have an HPV infection at some point in our lifetime and we’ll never know it.”
Nearly all sexually active Americans get HPV at some point in their lives, according to the Centers for Disease Control and Prevention. An estimated 80 percent of people are infected at some point, and most never realize it because the infection resolves itself on its own. But certain strains of the virus go on to cause cervical, vulvar, anal, penile, and oropharyngeal cancers.

 
Without the HPV vaccine, men in particular are put at risk of developing neck and throat cancers. Unlike cervical cancers, which can be detected with regular Pap smears, there’s no way to screen men.

 

Sturgis treats mostly middle aged male patients, and he estimated that about 60 percent of the cancers he deals with are caused by HPV. He said it’s important to increase the rates of vaccination among both girls and boys because it will be another 30 to 40 years before today’s kids hit the point when these type of throat cancers may start displaying themselves.
“To let your kids potentially suffer later in life is just a tragedy. That’s really the message here,” he said.

 
Both cancer doctors are optimistic that once more parents are educated about what’s at stake, they’ll start vaccinating their kids at higher rates. There’s a big information gap — one recent study found that 70 percent of U.S. adults didn’t realize the HPV vaccine has any connection to cancer whatsoever — that they believe can be corrected with more investment from primary care doctors who are on the front lines of recommending the shots.

 
“It’s really about empowering parents and health care professionals, and making them recognize that this is a childcare responsibility and a priority for all of us,” DePinho said. “It begins with interviews like this and just having the media getting this information out there.”

 
“Doctors are probably not as good at messaging to the public as we could be. We need some help,” Sturgis agreed.

 

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
December, 2014|Oral Cancer News|

Immune-related gene may predispose to HPV-related cancer

Source: bcm.edu
Author: Julia Parsons
 

An international coalition of cancer specialists led by a researcher now at Baylor College of Medicine has identified an immune related gene called transforming growth factor beta receptor 1 (TGFBR1) that appears to play an important role in determining whether a person develops a cancer related to human papilloma virus (HPV). HPV is, in particular, associated with anal cancer and cancers of the cervix, and the head and neck.

Their findings appear in the journal Cancer Research.

Until recently, head and neck cancer has been found primarily in smokers, but there has been a rise in HPV-associated head and neck cancer in nonsmokers. The head and neck cancer most-associated with HPV is oropharyngeal cancer, involving the tonsils and base of the tongue.

HPV is also one of the most common sexually transmitted diseases, with certain strains known to cause head and neck and/or cervical cancer.

The National Cancer Institute predicts that HPV-positive oropharyngeal cancer will likely surpass cervical cancer as the most common HPV-associated cancer in the United States by 2020.

“The real mystery is that in western countries, pretty much everyone is exposed to HPV but only a small number of people get HPV-related cancers,” said Dr. Andrew Sikora, vice-chair for research in the Department of Otolaryngology Head and Neck Surgery at Baylor. “We are trying to figure out what makes the people who actually get the cancer different from those who don’t, given that so many people are exposed.”

Using data collected as part of a genome-wide association study of head and neck cancer performed by the INHANCE consortium, the researchers were able to associate alterations in a number of immune-related genes with oropharyngeal cancer. One of these genes, TGFBR1, was found to be deregulated in patients with both oropharyngeal and cervical cancer.

“The fact that we were able to independently replicate our findings in two-different HPV-related cancers is exciting because it suggests that we have found something that is critical to the biology of how HPV causes cancer,” said Sikora, also co-director of the head and neck cancer program in the NCI-designated Dan L. Duncan Cancer Center Baylor.

“We hope to learn more about this gene and how it affects cancer,” Sikora added. “In the future we hope to develop a tool to identify who is more susceptible to HPV-related cancers.”

Sikora conducted the study while on faculty at the Icahn School of Medicine at Mount Sinai in New York prior to joining the Baylor faculty in July 2014. Co-author, Paolo Boffetta, director of the Institute for Translational Epidemiology at ISMMS was one of the investigators for the original INHANCE study.

Others who took part in this study include:  Chaya Levovitz; John Finnigan; Sara Alshawish; Marshal R. Posner; Weija Zhang; Eric E. Schadt; Eric M. Genden and Paolo Bofetta; The Icahn School of Medicine at Mount Sinai in New York; Dan Chen and Emma Ivansson of Uppsala University, Uppsala, Sweden.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
October, 2014|Oral Cancer News|

Oscar Award winning composer Ryuichi Sakamoto is diagnosed with Throat Cancer

Author: Jun Hongo
Source: blogs.wsj.com/japanrealtime
 

World-renowned Japanese musician and composer Ryuichi Sakamoto says he has throat cancer and has canceled his scheduled shows and activities.

The Oscar-winning composer and anti-nuclear activist said Thursday that he was diagnosed with oropharyngeal cancer at the end of June.

“After much thought and consideration, I have decided to take time off of work in order to concentrate on treating it,” the 62-year-old said in a statement. “I promise to return after a full recovery.”

According to his management agency Avex Music Creative Inc., Mr. Sakamoto will step down as one of the directors of the Sapporo International Art Festival 2014, scheduled to start next week. He will also cancel live shows including a performance at Park Hyatt Tokyo on July 30.

Avex Music Creative said there is no time frame set for Mr. Sakamoto’s return, and that the artist will “dedicate all his time to treatment.” The agency declined to offer details on the current stage of Mr. Sakamoto’s cancer.

The pioneering musician debuted as a member of Yellow Magic Orchestra in 1978, playing a role in the emergence of electro pop and providing inspiration for a generation of electronic music and hip-hop producers. His creativity and prowess as a keyboard player, producer and composer extends to a large swath of genres and styles from pop rock to bossa nova. He won an Academy Award for composing the score music for Bernardo Bertolucci’s 1987 film “The Last Emperor,” a movie he also appeared in as an actor.

Among international honors bestowed on Mr. Sakamoto, he was named an Officier of the Ordre des Arts et des Lettres from the French government in 2009.

In addition to his work in music, producing and acting, Mr. Sakamoto has been one of the most vocal activists against nuclear power following the Great East Japan Earthquake in 2011.

He has also been a leading figure in recent moves to prevent outdated legislation being used to stop people dancing at nightclubs in Japan.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
 
July, 2014|Oral Cancer News|

High-Risk HPV Prevalent in Oropharyngeal Cancers

Author: Roxanne Nelson
Source: medscape.com
 

A larger percentage of oropharyngeal cancers might be related to human papillomavirus (HPV) than previously thought. The Centers for Disease Control and Prevention (CDC) reports that in a large sample of invasive oropharyngeal squamous cell carcinomas, 72% were positive for HPV and 62% were positive for high-risk HPV types 16 and 18, which are covered by the 2 commercially available vaccines (Gardasil, Merck & Co.;Cervarix, GlaxoSmithKline).

On the basis of these data, the CDC researchers suggest that vaccines could prevent most oropharyngeal cancers in the United States.

The vaccines are marketed mainly for the prevention of cervical cancer, but there is hope, and some evidence, that the vaccines might also protect against oropharyngeal cancer. For example, last year, the Costa Rica HPV Vaccine Trial found that the Cervarix vaccine reduced oral HPV infections in women by more than 90%.

However, the effect of the vaccines could vary by demographic factors; HPV prevalence differed by sex and race/ethnicity, the researchers note.

In their study, Martin Steinau, PhD, senior scientist at the CDC, and colleagues report that the current global incidence of oropharyngeal cancers is estimated to be 85,000 annually, although there is considerable geographic variation. In the United States, there are about 12,000 new cases diagnosed every year, and most are classified histologically as squamous cell carcinoma (OPSCC).

The retrospective analysis was published in the May issue of Emerging Infectious Diseases.

Study Details

Dr. Steinau and colleagues sought to determine prevalence of HPV types detected in oropharyngeal cancers in the American population, and to establish a prevaccine baseline for monitoring the impact of vaccination.

They examined oropharyngeal tumors from 588 patients.

HPV was detected in 403 of the 557 patients with OPSCC (72.4%), and 396 (71.1%) were positive for only 1 or no high-risk types. A single HPV type was detected in 68.4% of cases, and 3.9% of samples contained 2 types. In 7 cases, only low-risk HPV types were detected. High-risk HPV16 was present in 337 (60.5%) cases, HPV18 was present in 14 (2.5%) cases, and 331 (59.4%) cases were exclusively positive for these 2 types.

Other high-risk types, including HPV31, 33, 35, 39, 45, and 52, were found at low frequency, the researchers point out.

There were differences in prevalence based on sex and race/ethnicity. The prevalence of the high-risk HPV16 and HPV18 was lower in women than in men (53%vs 66%), and in non-Hispanic black than other racial/ethnic groups (31% vs 68% to 80%).

When the researchers conducted a multivariate analysis for high-risk HPV, only race/ethnicity emerged as a significant independent factor (P = .003). The odds for high-risk HPV infections were significantly higher for all other race groups than for non-Hispanic black patients (P < .001).

When only HPV16/18 detection was considered, there were significant differences between those infected and those not infected for sex (P = .009) and race/ethnicity (P < .001), but not for age (P = .063).

“Future assessments are needed to monitor general prevalence and possible type-specific shifts,” the researchers conclude. “Data from the present and future studies will provide a baseline for early assessment of vaccine effects.”

This project was supported in part by CDC grants and federal funds for Residual Tissue Repositories from the National Cancer Institute SEER Population-based Registry Program, National Institutes of Health, Department of Health and Human Services. Coauthor Brenda Y. Hernandez reports receiving consultation and speaker fees from Merck and Co.

 

* This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

May, 2014|Oral Cancer News|

Study finds the prognosis of HPV positive tumors in head and neck cancer patients to vary depending on site

Source: sciencecodex.com
Author: Staff

 

Vienna, Austria: Patients with cancer of the throat and who are positive for the Human Papilloma virus (HPV+) have a good prognosis, but until now the effect of being HPV+ on the prognosis of tumours located elsewhere in the head and neck was unknown. Danish researchers have now shown that HPV status appears to have no prognostic effect on the outcome of primary radiotherapy in head and neck cancer outside the oropharynx (the part of the throat located behind the mouth, and which contains the soft palate and the base of the tongue), the ESTRO 33 congress will hear today (Sunday).

Presenting her results to the congress, Dr Pernille Lassen, MD, PhD, from the Aarhus University Hospital, Aarhus, Denmark, will say that head and neck cancers located outside the oropharynx should probably not be treated with the less intensive treatment strategies that are currently being investigated in clinical trials for HPV+ oropharyngeal tumours.

“HPV status has a very potent prognostic impact in radiotherapy for oropharyngeal cancer, and DNA from HPV has been found in all types of head and neck cancer, although it is far more common in oropharyngeal tumours. We decided to investigate the impact of HPV status in non-oropharyngeal cancers in the DAHANCA database, which includes all Danish head and neck cancer patients,” Dr Lassen will say.

The researchers searched the database to identify patients with locally advanced cancers who had been treated primarily with radiotherapy, and identified 1606 patients with larynx and pharynx carcinomas. Overall, 40% of the tumours were HPV positive, and the frequency was significantly higher in oropharyngeal cancer (57%), than in non-oropharyngeal (13%).

Being positive for HPV significantly improved tumour control (81% as opposed to 55%), as well as survival from the cancer (89% and 55% respectively), and death from any cause (82% and 38% respectively), after five years.

“In non-oropharyngeal cancers we found no prognostic impact of being HPV positive in any of these endpoints,” Dr Lassen will say. “This indicates that HPV status does not help us in predicting response to treatment, and hence the outcome of these cancers.

“We know from laboratory studies that HPV positive tumour cells are much more sensitive to radiation therapy than HPV negative cells, so until now we believed that they would behave similarly irrespective of site,” Dr Lassen will say. “However, these data indicate that this is not the case, and at present we do not understand why this should be, though it probably can be ascribed to other biological/genetic differences between the tumours rather than the HPV status. We would now like to try to elucidate the underlying mechanisms behind these different outcomes.”

There could be, for example, biological and/or genetic differences between the tumours other than the HPV status, the researchers say; for example, genetic changes caused by smoking tobacco, differences due to tumours of mixed make-up (for example, a combination of HPV+ and tobacco), or perhaps simply differences due to the site. “Such tumours with a combination of causes represent a challenge in our clinical daily practice,” Dr Lassen will say.

“We have started following up our work by analysing all the tumour samples using polymerase chain reaction, a way of amplifying DNA in order to be able to analyse changes in genetic information. We hope this will enable us to understand more about why the role of HPV in non-oropharyngeal tumours is so different. There are few data available on this subject at present, so finding out will be an important step towards optimising treatment for these patients.”

President of ESTRO, Professor Vincenzo Valentini, a radiation oncologist at the Policlinico Universitario A. Gemelli, Rome, Italy, commented: “These findings will have an important impact on the treatment of HPV+ head and neck cancers, and are likely to lead to a change in current practice.”

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

April, 2014|Oral Cancer News|

Effects of Chemoradiation on Voice and Speech Quality of H&N Cancer Patients

Source: Med Page Today
Published: February 23, 2014
By: Charles Bankhead
 

 

SCOTTSDALE, Ariz. — Patients with oropharyngeal cancer reported significant voice and speech impairment for up to 2 years after chemoradiation therapy, but most of their doctors saw no evidence of it, data from a prospective study showed.

Two years after treatment, a fourth of patients said their voice and speech remained below baseline levels, whereas none of their clinicians noted any impairment. At no time did as many as 10% of clinicians report patients with speech and voice issues, whereas the proportion of patients reporting problems ranged as high as 56%.

The likelihood of patient-reported difficulties with oral communication increased with the radiation dose to the glottic larynx, reported Jeffrey M. Vainshtein, MD, and colleagues at the Multidisciplinary Head and Neck Cancer Symposium.

“Our findings highlight the critical role of patient-reported outcomes in identifying areas of improvement of our current therapies, which may ultimately translate into improvements in quality of life for our patients,” Vainshtein, of the University of Michigan in Ann Arbor, said during a press briefing.

Dysphagia and xerostomia are recognized adverse effects of chemoradiation for head and neck cancer and have been studied extensively in recent years. In contrast, a paucity of information exists relative to the effects of chemoradiation on voice and speech quality, Vainshtein said.

To examine the issue, investigators assessed voice and speech outcomes in 93 patients who underwent chemoradiation for oropharyngeal cancer, using intensity-modulated radiation therapy (IMRT). At baseline, and then every 3 to 6 months after finishing treatment, patients completed two validated questionnaires: Head and Neck Quality of Life (HNQOL) and University of Washington Quality of Life (UWQOL).

At the same intervals, the patients’ physicians reported their assessments in accordance with the Common Terminology Criteria for Adverse Events.

All of the patients had locally advanced stage III/IV oropharyngeal cancer and received treatment in two clinical trials of organ-sparing IMRT. Radiation therapy protocols were designed to minimize the radiation dose to the pharyngeal constrictors, salivary glands, oral cavity, glottic larynx, supraglottic larynx, and esophagus.

Vainshtein and colleagues analyzed patient questionnaires to identify factors associated with voice and speech impairment, in addition to the frequency of impairment.

By the HNQOL communication domain and speech impairment domain of the UWQOL, radiotherapy-induced speech impairment reached a maximum in the first month after treatment. Impairment then decreased in subsequent assessments, stabilizing at 12 to 18 months.

The proportion of patients reporting post-treatment speech and voice impairment followed a time pattern consistent with speech impairment reflected in answers to the questionnaires. By the HNQOL, 68% of patients said their voice and speech quality were impaired versus baseline, decreasing to 56% at 3 months, 46% at 6 months, 33% at 12 months, 31% at 18 months, and 24% at 24 months.

By the UWQOL, the proportion of patients reporting worsening of voice and speech quality after treatment was 41%, 26%, 29%, 28%, 15%, and 22% at the assessments from 1 to 24 months after finishing therapy.

In contrast, few physicians included voice and speech impairment in their adverse event reports. Vainshtein said 7% of physicians reported grade 1 toxicity with respect to worsening of voice and speech at 3 months, 5% at 6 months, and 0% thereafter.

Comparing treatment characteristics and patient-reported voice quality worsening, investigators found an association between radiation dose to the larynx and patient-reported impairment at 6 and 12 months. Reported impairment at 6 months increased from 25% with a cumulative radiation dose of <20 Gy to 59% at >30-40 Gy, 50% at 40-50 Gy, and 64% with laryngeal doses >50 Gy (P=0.02).

A similar pattern emerged from the analysis of 12-month outcomes, as the proportion of patients reporting worsening of voice quality from baseline increased from 10% for laryngeal radiation doses <20 Gy to 63% of patients for cumulative doses >50 Gy (P=0.011).

“We observed similar findings for patient-reported voice quality worsening and speech impairment,” Vainshtein said. “The results were independent of other patient and treatment factors.”

Press briefing moderator Mitchell Machtay, MD, said he found the study eye opening.

“If you looked at radiation dose to larynx, not the area where the tumor was, I was struck by how doses of 20 to 30 Gy, which we don’t normally consider as very toxic high doses that can damage the voicebox, still caused a fair amount of damage,” said Machtay, of University Hospitals Case Medical Center in Cleveland.

The magnitude of disconnect between patient and physician assessments was one of the more surprising findings in the study.

“I don’t think it’s unique to head and neck cancer. I don’t think it’s unique to our study. I don’t think it’s unique to medicine,” Vainshtein said. “I think physicians tend to underestimate the effect of their treatment — whatever it is — on our patients.”

Some adverse effects can be subtle and do not become apparent during conversations with physicians, he continued. When the patients express their sentiments in a more formal manner, such as a questionnaire, the effects do emerge.

Some of the disconnect reflects differences in patients’ approaches to their illness and adverse effects of treatment, said Wade Thorstad, MD, of Washington University in St. Louis.

“There’s a group of patients, when you’re interviewing them about their symptoms, will tell it like it is and really explain things well,” said Thorstad, another participant in the press briefing. “There’s another group that is stoic, and they really underplay their issues before [their physician]. However, when they are filling out a questionnaire about their feelings about quality of life, I think you get a more honest assessment.”

 

* This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

 

February, 2014|Oral Cancer News|