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HPV in oral squamous cell carcinoma vs head and neck squamous cell carcinoma biopsies – a meta-analysis 1988-2007

  • 6/23/2008
  • Palermo, Italy
  • N Termine et al.
  • Ann. Onc., June 16, 2008

Introduction:
In the literature, there exists a wide range of human papillomavirus (HPV) DNA prevalence for head and neck squamous cell carcinoma (HNSCC), especially in relation to methods of viral detection and the lesion site. We estimated the pooled prevalence of HPV DNA in biopsies of HNSCC generically grouped versus oral squamous cell carcinoma (OSCC) in relation to the method of viral DNA detection, with the primary end point of verifying if these two variables (specification of tumour site and method of HPV DNA identification) influence the datum on HPV assay.

Methods:
By means of MEDLINE/PubMED/Ovid databases, we selected studies examining paraffin-embedded (PE) biopsies of HNSCC and OSCC. According to the inclusion criteria, 62 studies were analyzed. The following data were abstracted: sample size, HPV DNA prevalence, methods of detection [PCR and in situ hybridization (ISH)] and HPV genotypes. After testing the heterogeneity of the studies by the Cochran Q test, metanalysis was performed using the random effects model.

Results:
The pooled prevalence of HPV DNA in the overall samples (Sigma: 4852) was 34.5%, in OSCC it was 38.1% and in the not site-specific HNSCC was 24.1%. With regard to the detection method, PCR-based studies reported a higher prevalence rate than ISH-based rates (34.8, versus 32.9%) especially in the OSCC subgroup (OSCC PCR based: 39.9%).

Conclusion:
These findings support the assumption that a correct distinction of HNSCC by site, together with the use of more sensitive HPV DNA detection methods, should be considered as essential prerogatives in designing future investigations into viral prevalence in head and neck tumors.

Authors:
N Termine, V Panzarella, S Falaschini, A Russo, D Matranga, L Lo Muzio, and G Campisi

Authors’ affiliation:
Department of Oral Sciences, Section of Oral Medicine, University of Palermo, Palermo, Italy

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June, 2008|Archive|

George Moore, 88; doctor linked mouth cancer to chewing tobacco

  • 6/23/2008
  • Los Angeles, CA
  • Thomas H. Maugh II
  • Los Angeles Times (www.latimes.com)

Dr. George E. Moore, the cancer researcher who was among the first to link chewing tobacco to mouth cancer and who built the Roswell Park Memorial Institute in Buffalo, N.Y., into a major cancer research center, died May 19 in Conifer, Colo. He was 88. The cause of death was bladder cancer, according to his family.

George E. Moore also discovered the use of fluorescent and radioactive materials to diagnose and localize brain tumors, was a pioneer in the use of chemotherapy to treat breast cancer, and developed techniques for growing tumor cells in a laboratory.

When Moore did his first studies of tobacco chewing in the 1950s, there was little strong evidence linking smoking and lung cancer and virtually none tying tobacco to other cancers.

In a seminal 1954 paper, Moore and colleagues from Roswell Park and the University of Minnesota reported on 40 men who suffered from oral cancer. They found that 26 of them had chewed tobacco, most for 15 years or longer. The paper presented the first evidence that chewing tobacco could be as lethal as smoking it.

Extending their studies, they also found that many people who chewed but did not yet have mouth cancer had gum irritation and leukoplasia — white spots or patches on the interior of the mouth that are often a forerunner of cancer.

His discoveries put Moore on the leading edge of tobacco research for more than 15 years, but it was hard work because of the efforts of tobacco companies. When he tried to procure tobacco seedlings so he could grow his own plants, for example, he was unsuccessful until the husband of a woman he had treated for breast cancer provided some.

In his later life, he was pessimistic about his effort.

“With all of our scientific things, working as hard as we did, I don’t think we influenced smoking very much,” he told the Denver Post. “I think it became a socially accepted thing not to smoke, and that did more to change smoking habits than all of our scientific things.”

George Eugene Moore was born Feb. 22, 1920, in Minneapolis. He attended the University of Minnesota, receiving his medical degree in 1947 and a doctorate in surgery in 1950.

He spent his early career at the University of Minnesota Medical School and at age 32 was named head of Roswell Park, then a struggling research institute with two aging buildings.

By the time he left in 1967, the institute, now known as the Roswell Park Cancer Institute, had grown to cover seven city blocks.

“He was a role model for oncologists and a highly successful administrator,” said Dr. Donald L. Trump, current president and chief executive of the institute.

Moore left the institute when he was appointed director of public health research for the state of New York. He held the post until 1973, when he moved to Denver to join the University of Colorado School of Medicine. He spent the rest of his career there.

When Moore began his research, the primary treatment for breast cancer was surgical removal of the tumor. In the early 1960s, working with Dr. Rudolph Noer of the University of Louisville, Moore began supplementing surgery with the chemotherapeutic drug thiotepa.

They found that the drug could prevent or delay the recurrence of tumors in many patients. Unfortunately, it also triggered premature menopause; the drug gave way to more effective agents. But their study was among the first to show that chemotherapy could be useful in treating breast tumors.

Moore also developed chemical solutions that could be used to grow tumor cells in a laboratory, refusing to patent the technique so that it could be widely used. In the basement of his Denver office were nearly 1,000 such tumor lines, some of which had been kept alive 20 to 30 years. He called them “patients in a bottle.”

Moore had a variety of interests outside oncology. He dabbled in metalworking, creating a 7-foot-tall sculpture of the cross-section of a cell that he displayed in his frontyard.

He also studied the geology of Colorado and was a past president of the Colorado Mineral Society.

He met his wife of 63 years, the former Lorraine P. Hammell, while hitchhiking to an airport outside Minneapolis to take flying lessons.

In addition to his wife, he is survived by two sons, Allan of Acton, Mass., and Donald of Conifer; three daughters, Cathy of Tucson, Laurie of Davis, Calif., and Linda of Golden, Colo.; two brothers, John of Minneapolis and Robert of San Jose; a sister, Elizabeth Severson of Minneapolis; eight grandchildren; and three great-grandchildren.

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June, 2008|Archive|

Cost of Initial Cancer Care Climbed Between 1991 and 2002, as Radiation and Chemotherapy Treatments Increased

  • 6/23/2008
  • web-based article
  • staff
  • JNCI J Natl Cancer Inst Volume 100, Number 12 Pp. 829

The cost of cancer care incurred during the period two months prior to cancer diagnosis and 12 months following diagnosis increased substantially between 1991 and 2002 for elderly patients in the United States, according to a study published online June 10 in the Journal of the National Cancer Institute. The increases in costs for breast, lung, and colorectal cancer were due in large part to increases in the percentage of patients receiving radiation therapy and chemotherapy and the rising costs for those therapies.
There have been general reports of increases in the cost of cancer care, but little research has examined the magnitude of those changes or the type of treatments that are driving them.

To find out, Joan L. Warren, Ph.D., of the National Cancer Institute in Bethesda, Md., and colleagues analyzed data from the Surveillance, Epidemiology, and End-Results (SEER)-Medicare linked database. They identified 306,709 individuals aged 65 or older who were diagnosed with breast, lung, colorectal, or prostate cancer between 1991 and 2002. The researchers compared the cost of initial cancer treatment, separating cancer-related surgery, chemotherapy, radiation therapy, and other hospitalization.

During the study period, the average cost per lung cancer patient rose by $7,139 to $39,891, after adjusting for inflation. Similarly, the cost per colorectal cancer patient climbed by $5,345 to an average of $41,134, and per-patient breast cancer care rose by $4,189 to an average of $20,964. The cost of per-patient prostate cancer care declined by $196 during the same period to an average of $18,261 in 2002. The decline in the cost of prostate cancer care was due to a reduction in the number of men undergoing surgery as treatment for their prostate cancer. The total cost of initial care for patients with these four cancers was $6.7 billion in 2002.

Warren and colleagues note that the fraction of lung, colorectal, and breast cancer patients who received chemotherapy increased over the study time. That rise, combined with the higher cost of newer drugs, accounted for a substantial fraction of the increases in cost of care. And this increase, they suggest, is an underestimate because the most expensive agents did not gain U.S. Food and Drug Administration approval until after the study period. The authors note, however, that the cost of hospitalizations still accounted for the largest fraction of care in all four cancers.

These new data need to be considered by policy makers, according to the authors. “These data do not reflect the current (2008) or future costs to the Medicare program related to cancer care. Expensive chemotherapies will place a strain on the financial resources of the Medicare program. [Center for Medicare and Medicaid Services] needs to anticipate the burden of paying for new chemotherapies and may need to promote programs to identify those patients who may benefit the most from these expensive treatments,” the authors write.

Citation:
Warren JL, Yabroff KR, Meekins A, Topor M, Lamont EB, Brown ML. Evaluation of Trends in the Cost of Initial Cancer Treatment. J Natl Cancer Inst 2008; 100:888–897

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June, 2008|Archive|

Primary Tumors Can Drive the Growth of Distant Cancers

  • 6/23/2008
  • web-based article
  • staff
  • Biocompare Life Science News (www.biocomare.com)

Primary tumors can encourage the growth of stray cancer cells lurking elsewhere in the body that otherwise may not have amounted to much, according to a new study in the June 13 issue of the journal Cell, a publication of Cell Press. As people age, most may have such indolent cancer cells given the sheer number of cells in the body, although their rarity makes them impossible to detect, the researchers said.

The primary tumors under study, which were derived from human breast cancers, seem to “instigate” the growth of other cancers by mobilizing bone marrow cells, which then feed the secondary tumors’ growth, they report.

One key to the process is the secretion of a substance known as osteopontin by the instigating tumor, a finding that may have therapeutic implications. Indeed, the researchers noted that osteopontin is present at elevated levels in women with metastatic breast cancer, supporting the notion that the new findings may hold clinical significance.

“If metastases depend on stimulation by primary tumors, interception of the signal through neutralizing antibodies” might block cancer spread, said Robert Weinberg of the Massachusetts Institute of Technology. “That’s still speculative, but it’s an interesting idea to ponder,” he added, noting that treatments today don’t specifically target metastases, which are responsible for the vast majority of cancer deaths.

The researchers noted that while the effects of the tumor microenvironment has been much studied, much less was known about how the systemic environment in the body contributes to tumor growth. Several earlier reports had shown that assorted bone marrow-derived cells can be incorporated to various extents into the supportive framework, or stroma, of tumors. However, it wasn’t clear whether tumors actively recruit stromal cells by directly perturbing other cell reservoirs, such as the bone marrow, or whether tumors are just passive recipients of stromal cell precursors that normally circulate throughout the body.

In the new study, the researchers injected “instigating” human tumor cells into mice along with indolent “responding” cancer cells also derived from humans. Those indolent cells formed vigorously growing tumors only in the presence of the instigating tumor cells, they reported. They found further evidence that the instigating tumor somehow perturbs the makeup of the bone marrow, although Weinberg said they don’t really know how that happens. They also show that osteopontin is necessary to the process, but that it does not act alone.

Finally, they showed that the same instigation process can encourage the growth of disseminated metastatic cancer cells. Instigating breast tumors in the mice also drove the growth of implanted fragments of human colon tumors, a finding that they said shows the generality of the physiologic signaling.

Nonetheless, the researchers said they don’t yet know how universal this systemic instigation of tumor growth might be. Still, the findings challenge the “prevailing view that primary tumors suppress the growth of derived metastases,” Weinberg said. “We argue they can foster cancer’s spread by activating bone marrow that is then recruited by distant metastases.”

The findings also have important implications for the preclinical study of human cancers, Weinberg emphasized.

“The ability of instigating tumors to foster the growth of a human colon tumor surgical specimen underscores the powers of systemic instigation,” the researchers wrote. “Indeed, to our knowledge, methods to expedite the growth of human tumor surgical specimens in vivo have not been previously described. These results suggest that the presently described procedure can be used to study aspects of human tumor biology that would otherwise be difficult if not impossible to study.

“In the longer term, identification of additional tumor-derived factors that perturb the host systemic environment in one way or another may allow one to predict the effects that a given primary tumor type has on the outgrowth of indolent cancer cells that have disseminated to distant sites.”

Note:
1. Researchers include Sandra S. McAllister, Whitehead Institute for Biomedical Research, Cambridge, MA; Ann M. Gifford, Whitehead Institute for Biomedical Research, Cambridge, MA; Ashley L. Greiner, Whitehead Institute for Biomedical Research, Cambridge, MA; Boston University, Boston, MA; Stephen P. Kelleher, Whitehead Institute for Biomedical Research, Cambridge, MA, Williams College, Williamstown, MA; Matthew P. Saelzler, Whitehead Institute for Biomedical Research, Cambridge, MA; Massachusetts Institute of Technology, Cambridge, MA; Tan A. Ince, Whitehead Institute for Biomedical Research, Cambridge, MA; Brigham and Women’s Hospital, Harvard Medical School, Boston, MA; Ferenc Reinhardt, Whitehead Institute for Biomedical Research, Cambridge, MA; Lyndsay N. Harris, Yale University Medical Center, New Haven, CT; Bonnie L. Hylander, Roswell Park Cancer Institute, Buffalo, NY; Elizabeth A. Repasky, Roswell Park Cancer Institute, Buffalo, NY; and Robert A. Weinberg, Whitehead Institute for Biomedical Research, Cambridge, MA, Massachusetts Institute of Technology, Cambridge, MA, MIT Ludwig Center for Molecular Oncology, Cambridge, MA.

2. Source: Cell Press

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June, 2008|Archive|

Care for Caregivers

  • 6/21/2008
  • web-based article
  • staff
  • www.wqad.com

Clinical trials are generally for a patient, not the people taking care of the patient. But a new study focuses on the caregiver and how support can help everyone involved.

More than 50 million Americans are caregivers.

Their help saves the health care system more than three-hundred billion dollars a year. That’s why a new clinical trial focuses on educating the caregiver.

Study manager Darlene Johnson is passionate about this research because she is a tongue cancer survivor.

Her husband was her caregiver.

“I went home and told him about the study, and he said, ‘ah, man. I wish I had something like that when you were going through this,’ because he felt very insecure himself.”

For the study, caregivers will have one-on-one time with a nurse and receive this home care guide book.

Some of the advice:

Take time to rest — devote at least 30 minutes a day to yourself.

Be open in your conversations with the patient — talk about life and death.

Watch for signs of depression, and let the sick person make as many decisions as possible.

“I think this training will be invaluable.”

The study at Moffitt Cancer Center is open to patients and their caregivers for the next year. To qualify for the trial, patients must be older than 70 years of age and have a diagnosis of colon cancer or non-Hodgkin lymphoma.

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June, 2008|Archive|

Human Papillomavirus and Oral Cancer – Looking Toward the Clinic

  • 6/18/2008
  • web-based article
  • Caroline McNeil
  • JNCI Journal of the National Cancer Institute 2008 100(12):840-842

Head and neck cancer researchers are considering clinical studies, including a proposed cooperative group treatment trial, that would investigate the link between human papillomavirus (HPV) and some oral cancers. Although the studies are still in the planning stage, they mark a new turn toward the clinic for an area that up to now has centered mostly on epidemiologic and laboratory studies.

Over the past decade, population studies have established an association between HPV and some tumors in the oropharynx (tonsils, soft palate, posterior pharynx, and base of tongue). Much remains unknown about the biology and natural history of oral HPV infection, but evidence of its association with these tumors is so strong that the International Agency for Research on Cancer concluded, in a monograph published in December, that there is “sufficient evidence in humans for the carcinogenicity of HPV16 in the oral cavity and oropharynx.”

Now researchers are beginning to ponder the clinical implications of this link. Especially intriguing to many are data suggesting that HPV-positive oropharyngeal tumors respond better to treatment than HPV-negative tumors. That finding has given rise to important clinical questions, including the one to be addressed in the proposed trial: Can HPV-positive tumors be treated less aggressively than HPV-negative tumors because of their increased sensitivity to chemotherapy and radiotherapy?

“That’s the fundamental question,” said Arlene Forastiere, M.D., a professor at the Johns Hopkins Kimmel Cancer Center in Baltimore and a leader in the Eastern Cooperative Oncology Group, which is discussing the possibility of such a trial. “Should they be treated the same or differently?”

The difference in response rates is not the only aspect that sets HPV-positive tumors apart from HPV-negative tumors. Studies suggest that the tumors have different molecular and histologic features, that HPV-positive patients survive longer, and that their risk factors and demographics are distinct. HPV-positive patients are more likely to be young and less likely to smoke cigarettes or use alcohol than HPV-negative oral cancer patients. A prospective study published last year in the New England Journal of Medicine showed that HPV-positive tumors were strongly associated with multiple oral sex partners. Most recently, a case–control study ( J Natl Cancer Inst 2008;100:407–20) showed that HPV-positive oropharyngeal tumors are not influenced by alcohol or tobacco use, setting them apart from HPV-negative tumors, which are strongly associated with drinking and smoking.

“The risk factors are completely distinct and do not overlap,” said Maura Gillison, M.D., Ph.D., a Hopkins cancer researcher and lead author on this study as well as the New England Journal of Medicine article. “These are actually completely different cancers that happen to occur in the same place,” she said.

Others demur. This is “very groundbreaking work,” said Jatin Shah, M.D., chief of the head and neck service at Memorial Sloan-Kettering Cancer Center in New York, “but it remains to be proven that these are distinct pathological entities.” Tissue samples from HPV-positive and HPV-negative tumors look alike, he argues. And although HPV-positive patients have a better chance of responding to chemoradiation, the reasons are unknown. “This is a very provocative question,” he said. “We need more research in the lab to answer it.”

The question is particularly urgent in oropharyngeal cancer because of the acute and prolonged toxicity of current treatments, Shah said. The treatment can result in lifelong problems with swallowing and speech. And for HPV-positive patients, who are more likely to be young, that can mean many decades of severely impaired quality of life.

Still Hypothetical

Nevertheless, Shah and others warn against modifying the standard treatment now. Forastiere, who chairs the head and neck committee of the National Comprehensive Cancer Network, said that “it would be premature to make practice changes … quite dangerous, really.” The cancer network’s 2008 treatment guidelines for orophyryngeal cancer will not mention HPV status, she said. “The next steps are really in clinical trials.”

The link between HPV and oropharyngeal cancer also raises the possibility of targeting those tumors with a therapeutic vaccine. At Hopkins, Gillison and her colleagues have completed a phase I trial with an experimental treatment vaccine and are now analyzing the data. After 2 years of follow-up, she said, all 18 patients in the trial were doing well.

And if further studies confirm that HPV-positive patients have better response rates and survival, their improved prognosis could affect the staging system for head and neck cancers. Though a long way off, that possibility is already the subject of conjecture. Gillison said that, someday, HPV-positive and HPV-negative tumors might be staged as two separate diseases, in the way that small-cell and non–small-cell lung cancer are.

Shah, who chairs the head and neck section of the American Joint Committee on Cancer, which develops, maintains, and revises the tumor–node–metastasis staging system used in most cancers, said that one possibility would be to consider HPV status as an additional factor that influences prognosis. This factor may be considered in the future, he said, and could be similar to the way additional factors affect stage in other cancers. In thyroid cancer, for instance, anyone younger than 45 years is downstaged to a stage 1 or 2, even with distant metastases.

But HPV’s effect on oropharyngeal staging is still hypothetical, Shah emphasized. The joint committee is not considering any changes to the current system. “The time may come when HPV status will be a factor,” he said, “but there needs to be a lot more science before that.”

Prevention and Screening?

The link between HPV and oropharyngeal cancer also has potential implications for prevention. Will it ever be possible, for instance, to detect precancerous changes in the oropharynx, as in the cervix, with the help of HPV-based screening?

Detecting signs of oral HPV infection is not difficult—in oral rinses, for instance. But finding evidence that the viral DNA has been integrated into oropharyngeal basal cells and identifying submucosal, premalignant changes before they become visible is “a bit trickier,” Gillison said.

An even more fundamental barrier to screening is a lack of knowledge on how, or even whether, persistent oral HPV infection progresses to premalignant changes in the oropharynx.

“We don’t know what the infection looks like in premalignant cells. We don’t know if premalignant lesions in the oropharynx relate to HPV,” said Aimee Kreimer, Ph.D., in the division of cancer prevention at the National Cancer Institute in Bethesda, Md. “It’s so new. We don’t know the natural history of oral HPV infection.”

Shah said that studies are needed to show whether oral HPV infection progresses to dysplasia, as it does in cervical cancer. Doing so would take a prospective, longitudinal study of people with HPV infection, followed by visual detection of premalignant changes, he said. Or researchers might look for surrogate markers of progression by using random biopsies. “I don’t know if anyone is doing this, but it would be an exciting project,” he said. “It’s the logical next step.”

One smaller step toward understanding the natural history of HPV oral infection is a study, now in a pilot stage, designed to look at the persistence of these infections, Kreimer said. The study will be nested in a larger study—led by Anna Giuliano, Ph.D., at the H. Lee Moffitt Cancer Center in Tampa—which is monitoring men to evaluate anal and penile HPV infections.

Primary prevention of oropharyngeal cancers is another possibility that intrigues HPV researchers. Current HPV vaccines, designed to prevent cervical cancer, could theoretically prevent HPV-positive oropharyngeal cancers as well. Both Merck’s Gardasil and GlaxoSmithKline’s Cervarix (which was approved in Australia but not yet in the U.S.) target HPV16, which is implicated in most HPV-positive oropharyngeal cancers. And animal studies suggest that vaccination will prevent oral cancers. Hopkins researchers have proposed a prevention study to Merck, but when contacted for this article, a company spokesperson said that it is not currently working on plans for such a trial.

However, other studies may provide some data on this issue. Kreimer said that the NCI is considering adding an oral HPV component to its follow-up study of women in Costa Rica who participated in a trial of GlaxoSmithKline’s prevention vaccine. The study would compare the prevalence of oral HPV infection among women who received the vaccine with women who did not.

More studies—of all kinds—are likely. The NCI head and neck steering committee will convene a state-of-the-science meeting in November to help identify and prioritize research needs, said Claudio Dansky Ullmann, M.D., NCI’s lead for head and neck cancer trials, who serves on the steering committee. “We will bring the top experts in this area to discuss the current status of things and, we hope, to lay a platform plan for the development of future translational and clinical studies to advance the field,” he said.

And there seems little doubt that some of those studies, such as the proposed treatment trial, will explore whether HPV-positive and HPV-negative patients should be treated differently. “We find the data indicating that HPV-positive and HPV-negative cancers are distinct disease entities to be compelling,” Forastiere wrote in an e-mail. “Consequently, we are factoring this into clinical research questions and trial designs going forward.”

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June, 2008|Archive|

Researchers blame HPV for rise in throat cancer

  • 6/16/2008
  • Chicago, IL
  • staff
  • Newsday.com

For five grueling months in 2006 and 2007, Carol Kanga suffered through treatment for a life-threatening case of throat cancer linked to an unlikely source: a sexually transmitted viral infection.

Unable to swallow food or water during chemotherapy and radiation treatment, Kanga was fed through a stomach tube. Her one respite came on Thanksgiving, when she savored a single spoonful of weak broth.

“The radiation basically burns the skin off the outside and inside of your throat,” said Kanga, 52, a Rockville, Md., artist. “It’s like there’s a fire inside your neck.”

Kanga’s treatment was successful, but the virus that struck her is causing increasing concern among some researchers who think it is causing a small-scale epidemic of throat cancer.

That virus, scientists have proved only in the last two years, is human papillomavirus, or HPV — the same virus that’s behind most cases of cervical cancer.

With 6,000 cases per year and an annual increase of up to 10 percent in men younger than 60, some researchers say the HPV-linked throat cancers could overtake cervical cancer in the next decade.

“It’s almost a new disease, in a sense,” said Dr. Ezra Cohen, an oncologist at the University of Chicago Medical Center. “It’s now becoming a dominant sub-type of the disease that we see in our clinic.”

The HPV infections likely took root decades ago as the Baby Boomers were reaching adulthood, and only now are spurring a rise in throat cancer cases, mostly among men and women in their 50s.

No one understands the precise reason for the increase, though experts suspect it’s linked to changes in sexual practices that emerged in the 1960s and ’70s. For example, oral sex is a known risk factor for HPV-related throat cancers, and studies have shown that people who have come of age since the 1950s are more likely to have engaged in oral sex than those who were born earlier.

“Those people were in their teens during the sexual revolution, so they may be leading the wave,” said Dr. Maura Gillison, a professor of oncology and epidemiology at the Johns Hopkins Kimmel Cancer Center who has published numerous studies indicating that HPV-related throat cancer is a distinct type of disease.

The virus targets a specific portion of the upper throat called the oropharynx, which includes the tonsils and base of the tongue. Just a decade ago, doctors believed nearly all such cancers were linked with smoking or extremely heavy drinking.

Last year, however, Gillison’s team published a major study that found stark differences between the risky behaviors of throat cancer patients with HPV and those without. The HPV-positive cancer patients tended to have had higher numbers of sex partners than the others and were far more likely to have had multiple oral-sex partners.

Although Gillison had been methodically testing the HPV link to throat cancer since the late 1990s, she did not expect to see such clear signs that the cancer was hitting a distinct set of patients. The HPV-positive cancers even looked subtly different under a microscope.

“I realized it’s an absolutely different disease,” Gillison said.

Scientists think the virus causes cancer by commandeering part of a cell’s molecular machinery. It seems to interfere with the function of a key gene that normally would cause cells with potentially cancerous mutations to self-destruct.

The virus-linked cancer appears somewhat less deadly than throat cancers that arise from smoking or drinking. A paper published this year found that 96 percent of HPV-positive patients survived at least two years after diagnosis, compared with 62 percent survival for HPV-negative cancers.

“They have a better prognosis, but these are still very aggressive cancers,” said Dr. Marshall Posner, medical director of head and neck oncology at the Dana-Farber/Harvard Cancer Center in Boston.

While doctors had hoped for an overall drop in throat cancer as the percentage of Americans who smoke declined, the rise of HPV-related throat cancers seems to be offsetting any such benefit.

Gillison’s group tested hundreds of head and neck tumors that doctors began saving in the early 1970s, long before anyone knew such cancers might be linked to HPV. The work showed that the number of HPV-positive tumors increased by about 1 percent a year on average, though the trend has quickened in the last decade, especially in men younger than 60.

The virus thrives in the outer layer of skin and is transmitted mostly by skin-to-skin contact, researchers think. Sexual transmission tends to cause infection near the site of contact; intercourse is linked with cervical cancer, while oral sex can cause cancer of the upper throat.

Recent increases in HPV-positive throat cancers could be an aftershock of changes in sexual behavior that began decades ago. A landmark 1994 study of sexual behavior showed that oral sex had become commonplace only in the generations born in the 1950s or later. Fewer than 60 percent of people born in the 1930s were found to have had oral sex, compared with more than 80 percent of people born since 1950.

“The older people simply did not do it as much,” said Edward Laumann, a University of Chicago professor of sociology who led the National Health and Social Life Survey.

“It’s a very complicated social story that nobody’s really worked out in detail,” he said.

Other causes may have contributed to the spread of HPV cancers, including the increased movement of people around the country and the world in the last half-century, experts said. Scientists aren’t even sure yet whether the virus might be spread by kissing, though data suggest oral sex is a major route of transmission.

One implication of the cancer trend is that oral sex does not constitute “safe sex,” Kanga said.

“We can’t be afraid to talk about this,” Kanga said. “The message that oral sex carries risks is just not out there.”

Conservative groups say the emergence of HPV-related throat cancer is an additional argument for abstaining from sex until marriage.

But many researchers focus on expanded use of the HPV vaccine, which since 2006 has been recommended for girls ages 11 to 12. Just as the vaccine lessens the risk of cervical cancer for those girls, it may offer protection from HPV-positive throat cancer, though studies have not yet addressed that question.

Vaccine maker Merck & Co. Inc. hopes to submit an application this year to the U.S. Food and Drug Administration for use of its HPV vaccine in males. Although the company’s studies will not show specifically whether the vaccine protects against throat cancer, they should reveal whether the shots prevent infection with HPV.

“We expect the vaccine to work just as well in male and female populations,” said Dr. Richard Haupt, director of Merck’s clinical program for the vaccine, called Gardasil.

The prospect of one day wiping out an entire class of cancers with a vaccine is tantalizing to Gillison. The virus, while dangerous, also represents a sort of Achilles’ heel that is a rare find in cancer research.

“You know, most other cancers are going to be far more complicated than this,” Gillison said. “We found a cancer for which just one factor is necessary, and we’re pretty sure how to prevent that.”

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June, 2008|Archive|

HPV Vaccine for Boys – It Just Might Happen

  • 6/16/2008
  • Washington, D.C.
  • Dennis Thompson
  • US News & World Report (health.usnews.com)

More than half of all people will have a sexually transmitted disease or infection at some point in their life, the American Social Health Association reports.

Most HPV carriers are never diagnosed and never realize they carry the virus.

“It’s never detected, they are never aware of it, and their immune system suppresses it before they ever know about it in the vast majority of cases,” said Fred Wyand, spokesman for the American Social Health Association.

In this way, HPV is a silent killer. It’s the leading cause of cervical cancer and has become the second-leading cause of cancer death for women around the globe.

Doctors have responded to the threat of HPV by fighting it in a way unusual among sexually transmitted diseases — through a vaccine. The vaccine, Gardasil, is proven to prevent infection from four particularly dangerous strains of HPV in women. The U.S. Centers for Disease Control and Prevention has recommended that 11- and 12-year-old girls begin receiving the vaccine as part of school vaccination efforts.

Now researchers are looking into whether the vaccine should be given to boys as well, both to prevent the transmission of HPV, and to prevent the rarer, but no less deadly, cancers that can occur in men from the virus.

“There is probably no reason to think it would not be effective in boys, and because HPV is passed back and forth, immunizing a large part of the population would limit transmission,” said Dr. Jonathan L. Temte, associate professor in the Department of Family Medicine at the University of Wisconsin School of Medicine and Public Health.

“However, we’re still very early in the life span of this vaccine. It’s been less than a year since a recommendation was issued. It is premature to discuss giving it to boys until there’s proof of its efficacy,” added Temte, who also serves as the American Academy of Family Practitioners’ liaison to the Advisory Committee on Immunization Practices.

Studies have shown HPV to kill an estimated 240,000 women worldwide each year through cervical cancer. And infection with HPV via oral sex also has been proven to be the leading cause of throat cancer, striking 11,000 American men and women each year.

Research continues to find that Gardasil is very effective in preventing HPV-caused cervical cancer. Two studies last year involving almost 18,000 girls and women found that Gardasil was nearly 100 percent effective in preventing precancerous cervical lesions from the four HPV strains targeted by the vaccine. Though there are at least 15 strains of genital HPV, Gardasil targets the four strains thought to cause 70 percent of cervical malignancies.

The studies also found that Gardasil is much more effective when given to girls or young women before they become sexually active.

Although men don’t risk cervical cancer, they are half of the equation when it comes to sexually transmitted diseases. They also face increased risks for throat, genital and anal cancers from HPV infection.

The maker of Gardasil, Merck & Co., is accumulating data to consider whether boys should receive the inoculation as well.

“Nobody will be surprised if someday it is recommended for boys, but it’s premature to make that call now,” Wyand said. “The early returns I’m aware of with boys are positive. The vaccine appears to trigger an immune response similar to that of girls.”

Gardasil isn’t the only development on the vaccine front — other vaccines for sexually transmitted diseases are being studied as well, Temte said. A second HPV vaccine, this one from GlaxoSmithKline, is currently awaiting FDA approval, he said.

And researchers are also looking at a vaccine that could prevent herpes simplex, the cause of genital herpes. “There are going to be a few years out before we see anything like that,” Temte said.

Other news involving sexually transmitted disease is less encouraging.

The CDC estimates that approximately 19 million new sexually transmitted infections occur each year, almost half of them among young people ages 15 to 24. Direct medical costs associated with STDs consume up to $14.7 billion annually in the United States.

And, in 2006, there were increases in chlamydia, gonorrhea, and syphilis in the United States, according to the CDC.

More than 1.03 million cases of chlamydia were reported in 2006, up from 976,445 in 2005. Gonorrhea has increased for two years in a row, following a 74 percent decline in its reported rate for two decades. And the national syphilis rate increased 13.8 percent between 2005 and 2006, again reversing what had been years of decline.

Doctors are investigating what these increases mean, Wyand said.

“They aren’t sure if those were true increases, or if people are being tested with better and more specific technologies,” he said, noting that each of the STDs tend to be chronically underreported.

More information

To learn more about sexually transmitted diseases, visit the American Social Health Association

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President George W. Bush Names Waun Ki Hong, M.D., to National Cancer Advisory Board

  • 6/13/2008
  • Newport, PA
  • press release
  • PharmaLive.com

President George W. Bush today appointed world-renowned medical oncologist Waun Ki Hong, M.D., professor and head of the Division of Cancer Medicine at The University of Texas M. D. Anderson Cancer Center, to the National Cancer Advisory Board. Hong will serve a six-year term through March 9, 2014.

The function of the NCAB is to advise, assist and make recommendations to the secretary of the Department of Health and Human Services and the director of the National Cancer Institute. The NCAB may make recommendations regarding support grants and cooperative agreements, technical and scientific peer review, and functions pertaining to the NCI.

“I am delighted to be selected to serve on the National Cancer Advisory Board by President Bush. This new opportunity will allow me to share my expertise in translational and clinical research, to learn from and collaborate with so many of my distinguished colleagues around the country, and to continue to do my part to shape cancer policy,” said Hong. “My ultimate challenge, both at M. D. Anderson and soon with my work with the NCAB, is very simple: raising the bar in cancer care for all those with this disease.”

Since joining M. D. Anderson faculty in 1984, Hong has made seminal contributions to cancer medicine through his pioneering research in larynx preservation and chemoprevention in head and neck cancer.

Hong, author or co-author of more than 660 scientific publications, has successfully translated numerous key research findings into effective clinical care during his 30-year career in oncology. He was the first to demonstrate the efficacy of retinoids in reversing oral carcinogenesis, and in preventing secondary primary tumors in patients successfully treated for cancers in the head and neck.

When Hong began his research in the early 1980s, he was among just a handful of researchers exploring the concept of chemical intervention in the processes that lead to cancer, termed chemoprevention. Today, many scientists worldwide are pursuing chemoprevention studies for a number of disease, in part because of his innovative work.

Continuing an active research program in chemoprevention with multidisciplinary clinical trials, he is the principal investigator of BATTLE, a first-of-its kind individualized medicine program that provides the foundation for personalized targeted therapy for lung cancer.

“We are delighted that Dr. Hong has been appointed to the National Cancer Advisory Panel both for the honor it brings to him and M. D. Anderson, and because he will have the opportunity to advise on priorities and strengths that will speed up the effort to reduce mortality from cancer,” said M. D. Anderson President John Mendelsohn, M.D. “His many years as a clinical scientist at the forefront of cancer research and his broad experience at the nation’s leading cancer center, with its strong research, clinical and prevention programs, will help set the future agenda for cancer research and care in the United States.”

A native of South Korea, Hong earned his medical degree from the Yon Sei University of Medicine in Seoul, Korea. He joined M. D. Anderson in 1984 as chief of the Section of Head and Neck Medical Oncology. Dr. Hong became chair of the Department of Thoracic/Head and Neck Medical Oncology in 1993 and became head of M.D. Anderson’s largest clinical division, the Division of Cancer Medicine in 2001.

In 1996, he became the first M. D. Anderson physician to receive an American Cancer Society Clinical Research Professorship, a lifetime honor presented in recognition of his distinguished career. In 2001-2002, he served as president of the American Association for Cancer Research.

His many honors for outstanding achievements in clinical research and patient care include: the AACR’s Joseph H. Burchenal and the Rosenthal Foundation Awards; and the American Society of Clinical Oncology’s most prestigious award, the David A. Karnofsky Award.

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Screening for and diagnosis of oral premalignant lesions and oropharyngeal squamous cell carcinoma

  • 6/13/2008
  • web-based article
  • Joel B. Epstein et al.
  • Can Fam Physician Vol. 54, No. 6, June 2008, pp.870 – 8

Objective:
To describe the role that primary care physicians can play in early recognition of oral and oropharyngeal squamous cell carcinomas (OOSCCs) and to review the risk factors for OOSCCs, the nature of oral premalignant lesions, and the technique and aids for clinical examination.

Quality of Evidence:
Medline and Cancerlit literature searches were conducted using the following terms: oral cancer and risk factors, pre-malignant oral lesions, clinical evaluation of abnormal oral lesions, and cancer screening. Additional articles were identified from key references within articles. The articles contained level I, II, and III evidence and included controlled trials and systematic reviews.

Main Message:
Most OOSCCs are in advanced stages at diagnosis, and treatment does not improve survival rates. Early recognition and diagnosis of OOSCCs might improve patient survival and reduce treatment-related morbidity. Comprehensive head and neck examinations should be part of all medical and dental examinations. The head and neck should be inspected and palpated to evaluate for OOSCCs, particularly in high-risk patients and when symptoms are identified. A neck mass or mouth lesion combined with regional pain might suggest a malignant or premalignant process.

Conclusion:
Primary care physicians are well suited to providing head and neck examinations, and to screening for the presence of suspicious oral lesions. Referral for biopsy might be indicated, depending on the experience of examining physicians.

Authors:
Joel B. Epstein, DMD MSD FRCDC FDS
Professor in the Department of Oral Medicine and Diagnostic Sciences at the College of Dentistry and Director of the Interdisciplinary Program in Oral Cancer for the Illinois Cancer Center of the College of Medicine at the University of Illinois in Chicago

Meir Gorsky, DMD
Professor in the Department of Oral Medicine at Tel Aviv University in Israel and a Visiting Professor at the College of Dentistry at the University of Illinois

Robert J. Cabay, MD DDS
Resident in the Department of Pathology of the College of Medicine at the University of Illinois

Terry Day, MD
Associate Professor and Director of the Division of Head and Neck Oncologic Surgery in the Department of Otolaryngology-Head and Neck Surgery at the Medical University of South Carolina in Charleston

Wanda Gonsalves, MD
Assistant Professor in the Department of Family Medicine at the Medical University of South Carolina

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