Source: www.medscape.com
Author: staff

Immunization with a vaccine that targets the E6 and E7 oncoproteins of human papillomavirus-16 (HPV-16) prevents mice with HPV-16-positive head and neck squamous cell cancers (HNSCCs) from expressing these two oncoproteins by mounting a potent immune response.

The vaccine may become part of a treatment regimen, along with surgery, chemotherapy or radiotherapy, in patients with HPV-16-positive HNSCCs, investigators report in the December issue of the Archives of Otolaryngology, Head and Neck Surgery.

Dr. John H. Lee and colleagues at the Veterans Administration Medical Center in Iowa City generated an adenoviral recombinant vaccine expressing HPV-16 E6/E7 oncoproteins (adenovirus 5 (Ad5) E6/E7). Mice inoculated with the vaccine “completely cleared E6/E7-expressing tumor cells implanted 2 weeks after immunization.” (Dr. Lee is now at the Sanford School of Medicine, University of South Dakota, Sioux Falls.)

“A time course of interferon-gamma response showed that E6/E7-specific interferon-gamma production is significantly increased in the first 2 weeks after administration of the vaccine and is substantially maintained for up to 70 days,” the investigators report.

“At all dosages of vaccine, mice inoculated with Ad5 E6/E7 completely cleared E6/E7-expressing tumor cells implanted 2 weeks after either intratracheal or submucosal inoculation, with significant E6/E7-specific interferon-gamma production,” the team reports. “Inoculated mice cleared E6/E7-expressing tumor 70 days after implantation.”

“In accord with this, our data show that immunization with HPV-16 E6/E7 is an effective method for protecting a host from E6/E7-expressing HNSCCs via generation of a potent immune response,” Dr. Lee and colleagues write.

“Therapeutic vaccines may also be a practical option for patients with HPV-associated cancers such as those of the head and neck,” they conclude. “Combining immunotherapy with traditional treatment such as surgery, chemotherapy, or radiotherapy may be another option for improving the prognosis and quality of life of individuals with HPV-16-associated HNSCCs.”

Source:
Arch Otolaryngol Head Neck Surg 2008;134:1316-1323.

Source: American Association for Cancer Research
Author: staff

A study published in the journal Clinical Cancer Research, a journal of the American Association for Cancer Research, validates a non-invasive screening method with future potential for detection of human papillomavirus (HPV)-positive head and neck cancers.

In the study, researchers at Johns Hopkins University used oral rinses and targeted DNA amplification to track and identify oral HPV infections in patients with HPV16-positive and negative head and neck carcinomas (HNSCC) before and after therapy.

Findings showed detection of high-risk HPV infections in patients with HPV16-positive HNSCC for up to five years after therapy, indicating a high rate of persistent infection and reaffirming the connection between high-risk types of HPV and HPV-positive head and neck cancer.

“There is no question of cause,” said the study’s co-author Maura Gillison, M.D., Ph.D. associate professor of oncology. “It has now become a question of tracking the infection over time to identify those at risk of developing HPV-positive cancer, and for those who have had it, the risk of recurrence and risk of transmission. This is the first study in which we have been able to track the disease and related oral infections for an extended period of time.”

Researchers obtained oral rinse samples from a group of 135 patients with head and neck carcinomas. Tissue analysis showed that 44 of these patients had HPV16-positive tumors. Both the tissue and oral rinse samples were genetically sequenced to specify the HPV variants in each. Patients with HPV16-positive tumors were significantly more likely to have oral HPV16 infections, with an almost ten-fold increase prior to therapy and a fourteen-fold increase after. Patients with high-risk oral HPV infections prior to therapy also had a 44-fold increase of post-treatment infection.

Findings showed no significant odds of tumor recurrence among those with post treatment infections and no association between these infections and the development of second primary tumors at two years. However, this possibility cannot be excluded as longer observation may be needed.

Future studies will be able to use the data and methodology to further explore the connection between HPV and head and neck cancer formation, as well as the biological factors, such as HLA type, that are involved, Gillison said.

“The big question in HPV research is centered on biological factors that cause one person to have a medical consequence from an oral HPV infection and another to be able to clear the infection without any consequences,” Gillison said.

Funding for this study was provided by the Oral Cancer Foundation and the National Cancer Institute.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 28,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and 80 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. The AACR’s most recent publication and its sixth major journal, Cancer Prevention Research, is dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Source: www.reuters.com
Author: Reporting by Maggie Fox, editing by Will Dunham and Philip Barbara

The human wart virus HPV caused 25,000 cases of cancer in the United States between 1998 and 2003, including not only cervical cancer but also anal and mouth cancers, the U.S. Centers for Disease Control and Prevention reported on Monday.

The study suggests a broad need for screening both men and women for human papillomavirus, or HPV, another team of researchers, who did a similar survey, said.

HPV includes about 100 different viruses, and they are the leading cause of cervical cancer. The viruses, transmitted sexually and by skin-to-skin contact, can also cause anal and penile cancers, as well as cancers of the mouth and throat. HPV also causes common warts.

Both Merck and Co. and GlaxoSmithKline make vaccines against some of the strains of HPV most strongly linked with cervical cancer. They are recommended for girls and young women who have not begun sexual activity.

“This gives us baseline data to measure the impact of HPV vaccine and cervical cancer screening programs in reducing the incidence of cervical cancer and other HPV-associated cancers and precancers,” the CDC’s Dr. Mona Saraiya, who led the study, said in a statement.

Dr. Maura Gillison of Johns Hopkins University in Baltimore, who has studied the link between HPV and oral cancers, said the findings suggest a wider use of the cervical cancer vaccines may be justified.

“Currently available HPV vaccines have the potential to reduce the rates of HPV-associated cancers, like oral and anal cancers, that are currently on the rise and for which there is no effective or widely applied screening programs,” Gillison said in a statement.

Last month researchers said their computer model indicated that vaccinating women as old as 45 could prevent some cases of cervical cancer, even though the vaccines do not protect anyone who has already been infected with one of the strains of HPV.

An estimated 11,070 new cases of cervical cancer will be diagnosed in 2008 in the United States, and 3,870 women will die of it.

Cervical cancer is even more widespread globally where regular Pap smear and HIV tests are not available. An estimated 500,000 women globally are diagnosed with cervical cancer each year and 300,000 die of it.

The CDC survey of 38 states and Washington, D.C., found nearly 7,400 cancers of the mouth and throat that could be linked with HPV — nearly 5,700 among men and about 1,700 among women

“There were more than 3,000 HPV-associated anal cancers per year — about 1,900 in women and 1,100 in men,” the CDC said.

Source: www.canceraids.org
Author: staff

Professor Vivien Chen, PhD,. Associate Professor Xiao Cheng Wu, MD, PhD and Assistant Professor Edward Peters, DMD, SM, ScD, at LSU Health Sciences Center New Orleans School of Public Health contributed five papers to the largest most comprehensive assessment of the burden of human papillomavirus (HPV)-associated cancers in the United States to date. The report, “Assessing the Burden of Human Papillomavirus (HPV)-Associated Cancers in the United States (ABHACUS),” is available now online and will be published in the November 15, 2008 supplement to the journal Cancer.

The publication reports that 25,000 cases of HPV-associated cancers were diagnosed in 38 states and the District of Columbia from 1998-2003. These include cancers of the cervix, vagina, vulva, penis, anus, oral cavity and oropharynx. Human papillomaviruses comprise about 100 different types, more than 30 of which are sexually transmitted. As the data were collected prior to the development of the HPV vaccine, they will provide baseline incidence rates to determine the effectiveness of the vaccine as well as cervical cancer screening programs in reducing the incidence of HPV-associated cancers and precancers.

The most comprehensive analysis studied data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) cancer registries, including the Louisiana Tumor Registry at LSU Health Sciences Center New Orleans, and the Centers for Disease Control’s National Program of Cancer Registries.

The papers on which the LSUHSC public health faculty are co-authors are Incidence of in situ and invasive vulvar cancer in the US, 1998-2003 (p 2865-2872), Descriptive epidemiology of vaginal cancer incidence and survival by race, ethnicity, and age in the United States (p 2873-2882), Understanding the burden of human papillomavirus-associated anal cancers in the US (p 2892-2900), Burden of potentially human papillomavirus-associated cancers of the oropharynx and oral cavity in the US, 1998-2003 (p 2901-2909), and Cancer registries and monitoring the impact of prophylactic human papillomavirus vaccines: The potential role (p 3047-3057).

“The Louisiana Tumor Registry, housed in the LSUHSC School of Public health, has the academic infrastructure and expertise to monitor and evaluate the impact of HPV vaccination on the community,” notes Vivien W. Chen, PhD, Director of Louisiana Tumor Registry at LSU Health Sciences Center New Orleans School of Public Health.

“Incidence and mortality rates among African American women in Louisiana are significantly higher than both the rates of Louisiana white women and other African American women in the United States,” said Xiao Cheng Wu, MD, MPH, Associate Professor of Public Health and Associate Director of the Louisiana Tumor Registry at LSU Health Sciences Center New Orleans. “This observed black-white disparity can be reduced by equal access to and utilization of HPV vaccination.”

“As the Principal Investigator of two CDC funded projects in LA to examine the impact on cancer after introduction of the HPV vaccine I expect we will observe a decrease in HPV related cancers such as cervical and oral cancer,” said Edward Peters, DMD, ScD, Assistant Professor of Public Health at LSU Health Sciences Center New Orleans. “For example, about a third of oral cancers are due to HPV infection (the rest due to smoking and drinking) and oral cancers are twice as common in men than women. However, we currently do not vaccinate boys against HPV. We have tremendous opportunity to increase the level of cancer prevention for HPV associated cancers if our current HPV vaccination recommendations expand to include boys and young men .”

Source:
1. LSUHSC Public Health Contributes To Estimate Of HPV-Related Cancers

Source: Tampa Bay Online (www2.tbo.com)
Author: staff

Ten years ago, most of Brian Nussenbaum’s oral cancer patients were men older than 60 who used tobacco and drank heavily.

Today, his patients look different, as does the risky behavior that seems to be leading to their cancer.

Nussenbaum, an ear, nose and throat doctor at Washington University in St. Louis, estimates 70 percent of his cancer patients have tumors on the back of their tongues and tonsils caused by human papillomavirus-16. Most of those patients are between ages 45 and 55. About half are women.

And experts suspect that all of them - men and women - got the HPV from oral sex.

“We know now that 98 percent of cervical cancer is caused by HPV, and mostly HPV-16,” he says. “But no one talks about how you can also get mouth cancer from it.”

Researchers at Johns Hopkins Kimmel Cancer Center reported a link between HPV and these specific throat cancers in 2000. The increase in HPV oral cancer stems from a shift in sexual behaviors, combined with a dramatic decrease in the number of tonsillectomies performed. Cancer from the HPV virus often develops on the tonsils.

In a Johns Hopkins study, researchers concluded that people with HPV infections were 32 times more likely to develop oral cancer than those without HPV. These findings have ramifications for anyone who is sexually active.

Parents have another reason to think hard about whether they want their adolescent daughters, and perhaps even sons, vaccinated with Gardasil, a drug that helps protect against human papillomavirus. And even baby boomers who thought they had dodged the STD bullet, may not have after all.

Experts think the HPV lies dormant for years, perhaps decades, before causing the cancer. No one knows for how long because there’s so little data on the disease. The National Cancer Institute determined recently that the rate of oral cancer caused by HPV has risen steadily since 1973.

Source: www.sciencedaily.com
Author: staff

The human papillomavirus (HPV) allows infected cervical and head and neck cancer cells to maintain internal molecular conditions that make the cancers resistant to therapy and more likely to grow and spread, resulting in a poor prognosis for patients, researchers with UCLA’s Jonsson Cancer Center found.

Virtually all human cancers experience a state called intratumoral hypoxia, or a low amount of oxygen within the tumor. In the UCLA study, researchers showed that the HPV-positive cancers adapted to and took advantage of the hypoxic environment by expressing a protein that activates a cell signaling pathway that helps the cancers survive, grow and spread.

The study is published in the Nov. 4, 2008 issue of the journal Cancer Cell.

The research, done on cells in culture and in animal models, may lead to the development of new therapies that target the cell signaling pathway, thereby interrupting ability of the cancer cells to thrive, said Dr. Matthew Rettig, senior author of the study and a researcher at UCLA’s Jonsson Comprehensive Cancer Center.

“There is potential for therapeutic intervention based on this finding,” said Rettig, an associate professor of urology and medicine.

The finding is crucial because 90 to 98 percent of cervical cancers are caused by HPV. Cervical cancer is the second most common cancer in women worldwide, with more than 500,000 cases diagnosed annually. In all, 200,000 women die from cervical cancer every year. In oral cavity and pharynx cancers, the HPV virus is linked to about 20 to 40 percent of cases, caused by sexual behavior. About 400,000 cases of head and neck cancer are diagnosed worldwide each year, and more than half of those patients die of the disease.

In those cases where the cancer is HPV-positive, which number in the hundreds of thousands, the virus will make the disease more aggressive and deadly. Finding a way to stop the virus from prompting the cancers to grow and spread more quickly could save lives, Rettig said.

“The virus appears to be regulating the expression of genes that control all of the characteristics of hypoxic tumors, those that promote survival, drug resistance and the spread of the cancers,” Rettig said. “It’s good for the tumor, bad for the patient.”

In HPV-associated cancers, the HPV DNA is integrated into the cancer cell’s genome, where it expresses a protein called E6. In the cancer cell’s hypoxic environment, the protein targets a cell signaling pathway called NF-B, heightening its activation, Rettig said. This is the first time an association has been shown between the virus and hypoxia-induced activation of the cell signaling pathway.

The findings in the study happened by coincidence, Rettig said. He and his team were screening different cancer cell types for hypoxia-induced activation of the cell signaling pathway. When he looked at the results, Rettig noted that only the cancer cell types that were HPV-positive had heightened activation of the NF-B pathway. Cervical and head and neck cancers not caused by HPV did not have heightened activation of the pathway.

“The cells had to have the virus to have the activation,” he said.

The next step for Rettig and his team is to confirm the findings in additional animal models to gain broader understanding of the potential correlation of hypoxia and activation of the cell signaling pathway in humans. He hopes to have a drug to test in human clinical studies in about five years.

HPV is the most common sexually transmitted disease in the world. About 20 million Americans currently are infected with HPV, according to the Centers for Disease Control, and another 6.2 million people become newly infected each year. At least 50 percent of sexually active men and women will acquire genital HPV infection at some point in their lives.

In addition to cervical and head and neck cancers, HPV infection has been linked to vulvar, vaginal and other female genital cancers, as well as anal, penile and other male genital cancers.

Note:
Adapted from materials provided by University of California - Los Angeles, via EurekAlert!, a service of AAAS.

Source: healthhearsay.blogspot.com
Author: staff

A call to explore a broader use of HPV (human papillomavirus) vaccines and the validation of a simple oral screening test for HPV-caused oral cancers are reported in two studies by a Johns Hopkins Kimmel Cancer Center investigator.

Leading HPV expert Maura Gillison, M.D., Ph.D., the first to identify HPV infection as the cause of certain oral cancers and who identified multiple sex partners as the most important risk factor for these cancers, reports her latest work in the November 3, 2008, journal Clinical Cancer Research and in a Centers for Disease Control and Prevention (CDC) monograph. The CDC report on HPV-associated cancers appears on line November 3 and in the November 15, 2008, supplement edition of Cancer.

In the CDC report, believed to be the first and most comprehensive assessment of HPV-associated cancer data in the United States, investigators analyzed cancer registry data from 1998-2003 and found 25,000 cancer cases each year occurred at cancer sites associated with HPV infection. In additional analysis, Gillison and colleagues at the National Cancer Institute identified HPV infection as the underlying cause of approximately 20,000 of these cancers.

Gillison and team found approximately 20,000 cases of cancer in the United States each year are caused by HPV infection. Oral cancers are the second most common type of HPV-associated cancers and are increasing in incidence in the U.S., particularly among men. Add to that anal, penile, vaginal, and vulvar cancers that are also linked to HPV infection, and Gillison says these cancers, when combined, equal the number of cervical cancers, the most common and well known of the cancers caused by HPV.

While about one-quarter of HPV-linked cancers occur in men, vaccines are currently approved only for use in girls and young women for cervical cancer prevention. “We need to have a more comprehensive discussion of the potential impact the HPV vaccine could have on cancer rates among men and women in this country,” says Gillison, associate professor of oncology. “Currently available HPV vaccines have the potential to reduce the rates of HPV-associated cancers, like oral and anal cancers, that are currently on the rise and for which there no effective or widely-applied screening programs.” Gillison notes, however, that studies are needed to confirm that the vaccine effectively prevents HPV infections that lead to oral and anal cancers.

Gillison’s findings were part of a project known as ABHACUS (Assessing the Burden of Human Papillomavirus-Associated Cancers). The data studied came from the CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program. More than 80 investigators from across the country participated in the project, which addressed a variety of HPV-cancer associated issues, including racial disparity, economic impact, behavioral risk factors, and cancer mortality.

Other then prevention, early detection is held by cancer experts as the best way to control cancer. In the Clinical Cancer Research study, the first to track the disease and related oral infections over an extended period, Gillison found that simple “swish and spit” oral rinses can successfully track oral HPV infection over time. These findings open the door to a potential, non-invasive screening test to detect the disease and monitor for tumor recurrence. Head and neck cancer is the broad term for a variety of cancers of the oral cavity, including the tonsils, base of the tongue, and the side and back wall of the throat.

The study found that oral rinses successfully detected high-risk HPV infections in patients with HPV 16-positive head and neck cancers for up to five years after treatment for their cancer. Gillison says the findings indicate a high rate of persistent infection and reaffirms the connection between high-risk types of HPV and HPV-positive head and neck cancers.

In the study, the researchers used oral rinses to collect cells shed from inside the mouths of 135 head and neck cancer patients. The researchers genetically sequenced the DNA obtained from the rinses and tumor samples to identify those with HPV-positive cancers and determine the HPV type. There are approximately 120 types of HPV, but HPV 16 is one of the two most common associated with cancer.

The analysis revealed 44 patients with HPV 16-positive tumors and found that these patients were more likely to have continuing oral HPV 16 infections both before and after cancer treatment. While this study did not link the continued post-treatment infections to tumor recurrence, it was noted that patients with high-risk oral HPV infections prior to therapy, maintained high rates of infection after completing therapy. The team plans further, long-term research to determine if this continued infection leads to cancer recurrence.

In 2000, Gillison identified HPV-positive head and neck cancer as a distinct subtype of the disease and linked it to improved survival.

“There is no question of cause,” says Gillison. “It has now become a question of tracking the infection over time to identify those at risk of developing cancer or cancer recurrence.”

Other researchers participating in the study include Yuri Agrawal, Wayne M. Koch, Weihong Xiao, William H. Westra, Anna L. Trivett, and David E. Symer.

The research was funded by the Oral Cancer Foundation, the National Institute of Dental and Craniofacial Research, and the National Cancer Institute.

Source: newswire.ascribe.org
Author: staff

A call to explore a broader use of HPV (human papillomavirus) vaccines and the validation of a simple oral screening test for HPV-caused oral cancers are reported in two studies by a Johns Hopkins Kimmel Cancer Center investigator.

Leading HPV expert Maura Gillison, M.D., Ph.D., the first to identify HPV infection as the cause of certain oral cancers and who identified multiple sex partners as the most important risk factor for these cancers, reports her latest work in the November 3, 2008, journal Clinical Cancer Research and in a Centers for Disease Control and Prevention (CDC) monograph. The CDC report on HPV-associated cancers appears on line November 3 and in the November 15, 2008, supplement edition of Cancer.

In the CDC report, believed to be the first and most comprehensive assessment of HPV-associated cancer data in the United States, investigators analyzed cancer registry data from 1998-2003 and found 25,000 cancer cases each year occurred at cancer sites associated with HPV infection. In additional analysis, Gillison and colleagues at the National Cancer Institute identified HPV infection as the underlying cause of approximately 20,000 of these cancers.

Gillison and team found approximately 20,000 cases of cancer in the United States each year are caused by HPV infection. Oral cancers are the second most common type of HPV-associated cancers and are increasing in incidence in the U.S., particularly among men. Add to that anal, penile, vaginal, and vulvar cancers that are also linked to HPV infection, and Gillison says these cancers, when combined, equal the number of cervical cancers, the most common and well known of the cancers caused by HPV.

While about one-quarter of HPV-linked cancers occur in men, vaccines are currently approved only for use in girls and young women for cervical cancer prevention. “We need to have a more comprehensive discussion of the potential impact the HPV vaccine could have on cancer rates among men and women in this country,” says Gillison, associate professor of oncology. “Currently available HPV vaccines have the potential to reduce the rates of HPV-associated cancers, like oral and anal cancers, that are currently on the rise and for which there no effective or widely-applied screening programs.” Gillison notes, however, that studies are needed to confirm that the vaccine effectively prevents HPV infections that lead to oral and anal cancers.

Gillison’s findings were part of a project known as ABHACUS (Assessing the Burden of Human Papillomavirus-Associated Cancers). The data studied came from the CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program. More than 80 investigators from across the country participated in the project, which addressed a variety of HPV-cancer associated issues, including racial disparity, economic impact, behavioral risk factors, and cancer mortality.

Other then prevention, early detection is held by cancer experts as the best way to control cancer. In the Clinical Cancer Research study, the first to track the disease and related oral infections over an extended period, Gillison found that simple “swish and spit” oral rinses can successfully track oral HPV infection over time. These findings open the door to a potential, non-invasive screening test to detect the disease and monitor for tumor recurrence. Head and neck cancer is the broad term for a variety of cancers of the oral cavity, including the tonsils, base of the tongue, and the side and back wall of the throat.

The study found that oral rinses successfully detected high-risk HPV infections in patients with HPV 16-positive head and neck cancers for up to five years after treatment for their cancer. Gillison says the findings indicate a high rate of persistent infection and reaffirms the connection between high-risk types of HPV and HPV-positive head and neck cancers.

In the study, the researchers used oral rinses to collect cells shed from inside the mouths of 135 head and neck cancer patients. The researchers genetically sequenced the DNA obtained from the rinses and tumor samples to identify those with HPV-positive cancers and determine the HPV type. There are approximately 120 types of HPV, but HPV 16 is one of the two most common associated with cancer.

The analysis revealed 44 patients with HPV 16-positive tumors and found that these patients were more likely to have continuing oral HPV 16 infections both before and after cancer treatment. While this study did not link the continued post-treatment infections to tumor recurrence, it was noted that patients with high-risk oral HPV infections prior to therapy, maintained high rates of infection after completing therapy. The team plans further, long-term research to determine if this continued infection leads to cancer recurrence.

In 2000, Gillison identified HPV-positive head and neck cancer as a distinct subtype of the disease and linked it to improved survival.

“There is no question of cause,” says Gillison. “It has now become a question of tracking the infection over time to identify those at risk of developing cancer or cancer recurrence.”

Notes:
1. Other researchers participating in the study include Yuri Agrawal, Wayne M. Koch, Weihong Xiao, William H. Westra, Anna L. Trivett, and David E. Symer.
2. The research was funded by the Oral Cancer Foundation, the National Institute of Dental and Craniofacial Research, and the National Cancer Institute.

Source: www.newswise.com
Author: staff

The human papillomavirus (HPV) allows infected cervical and head and neck cancer cells to maintain internal molecular conditions that make the cancers resistant to therapy and more likely to grow and spread, resulting in a poor prognosis for patients, researchers with UCLA’s Jonsson Cancer Center found.

Virtually all human cancers experience a state called intratumoral hypoxia, or a low amount of oxygen within the tumor. In the UCLA study, researchers showed that the HPV-positive cancers adapted to and took advantage of the hypoxic environment by expressing a protein that activates a cell signaling pathway that helps the cancers survive, grow and spread.

The study is published in the Nov. 4, 2008 issue of the journal Cancer Cell.

The research, done on cells in culture and in animal models, may lead to the development of new therapies that target the cell signaling pathway, thereby interrupting ability of the cancer cells to thrive, said Dr. Matthew Rettig, senior author of the study and a researcher at UCLA’s Jonsson Comprehensive Cancer Center.

“There is potential for therapeutic intervention based on this finding,” said Rettig, an associate professor of urology and medicine.

The finding is crucial because 90 to 98 percent of cervical cancers are caused by HPV. Cervical cancer is the second most common cancer in women worldwide, with more than 500,000 cases diagnosed annually. In all, 200,000 women die from cervical cancer every year. In oral cavity and pharynx cancers, the HPV virus is linked to about 20 to 40 percent of cases, caused by sexual behavior. About 400,000 cases of head and neck cancer are diagnosed worldwide each year, and more than half of those patients die of the disease.

In those cases where the cancer is HPV-positive, which number in the hundreds of thousands, the virus will make the disease more aggressive and deadly. Finding a way to stop the virus from prompting the cancers to grow and spread more quickly could save lives, Rettig said.

“The virus appears to be regulating the expression of genes that control all of the characteristics of hypoxic tumors, those that promote survival, drug resistance and the spread of the cancers,” Rettig said. “It’s good for the tumor, bad for the patient.”

In HPV-associated cancers, the HPV DNA is integrated into the cancer cell’s genome, where it expresses a protein called E6. In the cancer cell’s hypoxic environment, the protein targets a cell signaling pathway, heightening its activation, Rettig said. This is the first time an association has been shown between the virus and hypoxia-induced activation of the cell signaling pathway.

The findings in the study happened by coincidence, Rettig said. He and his team were screening different cancer cell types for hypoxia-induced activation of the cell signaling pathway. When he looked at the results, Rettig noted that only the cancer cell types that were HPV-positive had heightened activation of this pathway. Cervical and head and neck cancers not caused by HPV did not have heightened activation of the pathway.

“The cells had to have the virus to have the activation,” he said.

The next step for Rettig and his team is to confirm the findings in additional animal models to gain broader understanding of the potential correlation of hypoxia and activation of the cell signaling pathway in humans. He hopes to have a drug to test in human clinical studies in about five years.

HPV is the most common sexually transmitted disease in the world. About 20 million Americans currently are infected with HPV, according to the Centers for Disease Control, and another 6.2 million people become newly infected each year. At least 50 percent of sexually active men and women will acquire genital HPV infection at some point in their lives.

In addition to cervical and head and neck cancers, HPV infection has been linked to vulvar, vaginal and other female genital cancers, as well as anal, penile and other male genital cancers.

UCLA’s Jonsson Comprehensive Cancer Center comprises about 235 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation’s largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2008, the Jonsson Cancer Center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for nine consecutive years.

Source: www.washingtonpost.com
Author: staff

Gardasil, the two-year-old vaccine that’s designed to prevent cervical cancer, is safe, U.S. officials said Wednesday. The U.S. Centers for Disease Control and Prevention’s Immunization Safety Office said a study of 370,000 doses given to girls and young women over the past two years found no evidence that the vaccine causes an increased risk of blood clots or other serious conditions, Bloomberg News reported.

The CDC, which recommends the vaccine for girls starting at ages 11 and 12, based its findings on statistics from the Vaccine Safety Datalink, which uses medical data to test hypotheses about vaccine safety, the news service said.

“There were no associations found that suggested an elevated risk,” said John Iskander, acting director for the Immunization Safety Office, toldBloomberg.

Critics of the vaccine, including some groups that worry that the inoculation could promote promiscuity, have contended that Gardasil may not be safe and could give women a false sense of security about sexually transmitted diseases.

Gardasil protects against four types of genital human papillomavirus, HPV, which is spread through sexual contact and can cause cervical cancer in women.

The U.S. study covered 190,000 girls and young women who received at least one dose of the vaccine’s three-shot regimen. The CDC researchers compared medical data on those girls who got the vaccine with data for girls and young women who received other vaccines or none.

“The results are really reassuring,” said Dr. Paul Offit, chief of the infectious diseases division at Children’s Hospital of Philadelphia. “There’s a public perception that the vaccine is not safe. This is important for countering negative information.”

CDC officials had announced earlier this month that an estimated 25 percent of girls aged 11 to 17 have gotten the vaccine.

“This is very good for a first-year measurement of a new vaccine,” Dr. Lance Rodewald, director of the Division of Immunization Services at the CDC’ National Center for Immunization and Respiratory Diseases, said during a Oct. 9 teleconference announcing the survey. “It usually takes six to nine years to achieve the desired 90 percent coverage.”

Rodewald noted that because the survey covered only young teens, many more young women have probably received the vaccine. The vaccine has been very well-tolerated, and its protection, especially when given at a younger age, is expected to last at least six years, he noted. Whether a booster shot will be needed isn’t known yet.

The hope for the vaccine is that it will reduce the almost 4,000 cervical cancer deaths each year in the United States. Barriers to getting the vaccine include cost, which is about $375, although it is covered under many health insurance plans.

One side effect associated with the vaccine, fainting, resulted in the U.S. Food and Drug Administration last month requiring that vaccine manufacturer Merck & Co. add a warning to the package insert, advising doctors to watch patients for 15 minutes after the shot to be sure they don’t faint.

In July, news stories said that almost 8,000 reports of adverse reactions to Gardasil — including injection site pain and nausea — had been filed with the CDC.

The reactions included 15 reports of death and 10 confirmed deaths, but none of the deaths has been tied to the vaccine, according to aCNNreport.

After the CDC study results were released Wednesday, Merck issued the following statement: “Gardasil is an important tool to help prevent cervical cancer caused by HPV types 16 and 18 for girls and young women. About 30 women every day are diagnosed with cervical cancer in the United States. An estimated 8 out of 10 women will become infected with HPV in their lifetime. For most people, HPV clears on its own. But for some women who don’t clear certain types of the virus, cervical cancer can develop. And there’s no way to predict who will or won’t clear the virus.”

Sources:
U.S. Centers for Disease Control and Prevention, Atlanta;Bloomberg News; Oct. 22, 2008, news release, Merck & Co.