DNA

HPV data may aid vaccine’s effectiveness

Source: health.usnews.com
Author: staff

The majority of invasive cervical cancers in New Mexico in the 1980s and 1990s contained DNA from human papillomavirus type 16 (HPV16) and HPV type 18 (HPV18), says a new study. It also found that women diagnosed with HPV16- or HPV18-positive cancers were an average of five years younger than those diagnosed with cancers associated with other HPV types. The HPV vaccine (Gardasil) protects against infections caused by HPV16 and HPV18, so the new findings may have implications for future cancer screening programs, the researchers said.

The researchers analyzed U.S. data in the Surveillance, Epidemiology and End Results registry and identified 1,213 cases of in situ cervical cancer diagnosed between 1980 and 1999, as well as 808 cases of invasive cervical cancer diagnosed between 1980 and 1999 in New Mexico.

HPV16 DNA was found in 53.2 percent of invasive cervical cancers, HPV18 DNA was found in 13.1 percent, and HPV45 DNA in 6.1 percent. HPV16 DNA was found in 56.3 percent of in situ cervical cancers, HPV31 DNA in 12.6 percent, and HPV33 DNA in 8 percent.

Patients’ median age at diagnosis of invasive cancer with HPV16 and HPV18 was 48.1 years, and 45.9 years, respectively. Median age at diagnosis of invasive cancer with other HPV genotypes was 52.3 years. The study is in the March 24 online issue of the Journal of the National Cancer Institute.

“To our knowledge, this is the largest study of its kind conducted in a U.S. population,” wrote a team led by Cosette M. Wheeler, of the University of New Mexico Health Sciences Center in Albuquerque.

“This study of HPV genotypes in New Mexico provides important baseline data for evaluating the effectiveness of nearly implemented HPV-based technologies, HPV vaccines, and HPV screening in the prevention of cervical cancer,” she said. “Moreover, these data can guide the future application of these technologies to maximize the cost-effective, public health benefits of these interventions.”

April, 2009|Oral Cancer News|

Discovery may result in new test to determine predisposition to cancer

Source: www.biocompare.com
Author: staff

Researchers at UCLA’s Jonsson Comprehensive Cancer Center have developed an assay that may be used to help identify new genes that can predict a predisposition to cancer. The study, published in the April issue of Radiation Research, was done in yeast and mammalian cells.

Cancer cells show persistent genetic instability and the researchers, led by Robert Schiestl, have discovered a mechanism that switches on that genetic instability. If they can uncover and understand the molecular pathways at work in promoting genetic instability, they may be able to develop ways to switch that mechanism off, restoring stability.

“We all have several hundred cells in our body that go crazy every day, and they’re taken out by our immune system,” said Schiestl, a professor of pathology, radiation oncology and environmental health sciences and a Jonsson Cancer Center scientist. “What’s important is that those cells don’t grow and spread and invade other regions of our body. Cancer cells are able to grow, spread and invade because the continued genetic instability can disturb the cellular program and create a growth advantage. Unfortunately, the immune system is not very effective at taking cancer cells out.”

The assay determines the efficiency of the repair mechanism when DNA suffers a double-strand break, when both strands in the double helix are severed. These breaks cause genetic instability and are particularly dangerous because they can lead to genome rearrangements or deletions of certain genes that, when gone, result in cancer.

“Every cell has double strand breaks all the time,” said Schiestl, senior author of the study. “It is how the cell tries to fix these breaks that is key, the capacity and the efficiency of the repair so no further harm occurs.”

A cell that can’t efficiently repair itself could result in cancer.

In the study, researchers irradiated cells to create double strand breaks. They wanted to determine if a double strand break occurs in one area of the DNA is the instability limited to that area or also evident elsewhere. The standard thinking was that the genetic instability would be localized to the area of the break. However, Schiestl and his team showed that a break in one area has an “in trans” effect, meaning the instability could surface anywhere.

“What we have shown now in this paper is that DNA damage at one position in the genome, causes a certain mechanism of genetic instability all over the genome,” Schiestl said.

Specifically, the team irradiated cells and then transformed them with a DNA fragment that detects the efficiency and the accuracy of double strand break repair. The key in this experiment was that the DNA fragment was not irradiated. In this way, the researchers could demonstrate that the radiation triggered a specific mechanism of double strand break repair in the DNA fragment that did not receive any radiation. The effect was still noticeable after almost all the DNA damage the radiation caused in the cells was repaired, showing that the mechanism that is induced by the radiation is independent of the actual damage caused by the radiation.

Schiestl had previously shown that a single DNA double strand break also induces genetic instability all over the genome at sites that are not damaged, again a proof that double strand breaks induce genetic instability in trans.

Interestingly, many cancer cells show an elevated induction of the specific DNA double strand break repair mechanism found induced in trans in this study, as if the cancer cells had this mechanism somehow induced and were not able to switch it off.

“Now we have to identify the mechanism of the pathway, identify the genes involved in inducing that pathway and that might give us targets that we can inhibit with drugs to try to reduce genetic instability,” Schiestl said. “That could lead to a cancer treatment. Any time you can stop the growth of a cancer, you’ve won. It doesn’t damage other tissues or spread to other organs. We might be able to stop the instability before it results in cancer.”

Note:
1. The research was funded in part by a National Institutes of Health grant and a NASA graduate student fellowship. Other members of Schiestl’s team included Zorica Scuric, Cecilia Chan and Kurt Hafer.

April, 2009|Oral Cancer News|

Genetic Changes Outside Nuclear DNA suspected to trigger more than half of all cancers

Source: www.newswise.com
Author: staff

A buildup of chemical bonds on certain cancer-promoting genes, a process known as hypermethylation, is widely known to render cells cancerous by disrupting biological brakes on runaway growth. Now, Johns Hopkins scientists say the reverse process — demethylation — which wipes off those chemical bonds may also trigger more than half of all cancers.

One potential consequence of the new research is that demethylating drugs now used to treat some cancers may actually cause new cancers as a side effect.

“It’s much too early to say for certain, but some patients could be at risk for additional primary tumors, and we may find that they need a molecular profile of their cancer before starting demethylating therapy,” says Joseph Califano, M.D., professor of otolaryngology–head and neck surgery and oncology at Johns Hopkins.

The findings, based on studies of normal and cancer cells from human mouth, nose and throat tissue, provide more evidence that important regulators of gene activity occur outside as well as inside DNA in a cell’s nucleus.

“While cancer-causing and other mutations alter vital protein-making pathways by rewriting the gene’s DNA code, epigenetic changes affect genes without changing the code itself. The new studies tell us that such changes occur not only when methyl groups bond to a gene’s on-off switch, but also when they come unglued,” says Califano.

Califano says sporadic reports of demethylation as a tool in activating cancer-promoting genes led his team to develop a systematic way to discover these epigenetic changes and show how the process is linked to cancer.

To gather their evidence, Califano and his group treated two cell lines from normal oral tissue with the demethylating drug 5-azacytidine and collected a list of genes that were activated as a result. They used special silicon chips carrying pieces of genetic material that allow thousands of genes to be analyzed at one time to locate genes activated by demethylation.

The list was cross-referenced with genes “turned on” in 49 head and neck cancer samples and 19 normal tissue samples. In all, Califano and his team found 106 genes specific to head and neck cancer that were activated by the demethylation process. “Some of the genes regulate growth, others metabolize sugars and some have already been linked to cancer development,” says Califano, who is director of head and neck cancer research at the Milton J. Dance Jr. Head & Neck Center at Greater Baltimore Medical Center. A report on this work appears on March 23 in PLoS One.

Further analysis by the Johns Hopkins team revealed a single connection among 106 genes: methylation within them is regulated by another gene called BORIS. BORIS acts as a “master regulator,” recruiting other proteins to demethylate a coordinated set of genes and signaling the development of cancer. According to the scientists, nearly 60 percent of a wide range of cancers, including head and neck and lung cancer, have high levels of BORIS expression.

He envisions that agents like 5-azacytidine may need to be combined with a “BORIS blocker,” a drug that has yet to be developed to protect patients who need demethylating therapies.

The research is funded by the Flight Attendant Medical Research Institute, the National Institute of Dental and Craniofacial Research, and the National Cancer Institute.

Research participants included Ian M. Smith, Chad A. Glazer, Suhail K. Mithani, Michael F. Ochs, Wenyue Sun, Sheetal Bhan, Andrew Gray, Chunyan Liu, Steven S. Chang, Kimberly L. Ostrow, William H. Westra, Shahnaz Begum and Mousumi Dhara from Johns Hopkins; and Alexander Vostrov, Ziedulla Abdullaev and Victor Lobanenkov from the National Institutes of Health.

Source:
Johns Hopkins Medicine

March, 2009|Oral Cancer News|

Perceptronix reports clinical study underway to evaluate OralAdvance(TM) for early detection of oral cancer

Source: www.earthtimes.org
Author: press release

Perceptronix Medical Inc. announces that a clinical study of OralAdvance(TM), a test for the early detection of oral cancer, is now underway. The clinical study will assess the performance of OralAdvance(TM) compared to the gold standard biopsy and histology for its ability to differentiate between visually suspicious oral lesions with cancer or pre-cancer and visually suspicious benign oral lesions.

“Unlike many other types of cancer, the incidence and mortality rates of oral cancer have not shown significant improvement over the past 30 years. By the time most oral cancers are diagnosed, they are already symptomatic late-stage disease. At Perceptronix we are dedicated to changing this paradigm towards early detection for better patient outcomes,” says Dr. Bojana Turic, President and CEO of Perceptronix.

Patients for the blinded study will be recruited from the BC Cancer Agency’s Vancouver and Fraser Valley Centres.

“We are pleased to be able to participate in the evaluation of the test in a clinical setting with technology that was developed in partnership with scientists at the BC Cancer Agency’s Research Centre, and we are hopeful that the test will have a positive impact on the early detection of oral cancer,” says Dr. Allan Hovan (Provincial Professional Practice Leader, Program in Oral Oncology/Dentistry, BC Cancer Agency).

Currently, the death rate for oral cancer is higher than that of cervical cancer, Hodgkin’s disease, cancer of the brain, liver, testes, kidney, or malignant melanoma. High death rate associated with oral cancer could be reduced significantly by putting clinical and technological emphasis on early detection.

– When oral cancer is detected in its later stages, the five-year survival rate is approximately 50%

– When oral cancer is detected in its early stage, the five-year survival rate is 80% or higher

– Currently, only 36% of all oral cancers are detected in their early stage.

About OralAdvance(TM)
OralAdvance(TM) is a new quantitative cytology test based on analysis of oral brush specimens. The test provides an objective measure of gross DNA abnormality to determine the pre-malignant or malignant nature of a lesion. OralAdvance(TM) offers a new and useful option to assess suspicious lesions when a biopsy is not warranted or possible.

About Perceptronix Medical Inc.
Perceptronix Medical Inc. (Vancouver, Canada) is a private cancer diagnostics laboratory specializing in the provision of innovative early cancer detection tests based on quantitative cytology. The Company’s DNA image cytometry technology was developed in partnership with the BC Cancer Agency (Canada). Quantitative cytology provides physicians with an innovative cytopathology assessment based on an objective measure of large-scale DNA abnormality that can indicate precancerous or cancerous changes. The company has developed proprietary tests for the early detection of lung cancer and oral cancer using its DNA cytometry technology and offers quantitative cytology analysis of various tissues.

February, 2009|Oral Cancer News|

Variations in gene DNA boost drinkers’ cancer risk

Source: www.washingtonpost.com
Author: staff

Variations in the DNA of certain genes can increase the risk of cancer in people who drink alcohol, according to researchers who reviewed studies on alcohol consumption, genetic polymorphisms and cancer.

Their analysis suggests that such variations, called gene polymorphisms, in two enzymes — alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) — involved in metabolizing alcohol significantly increase alcohol drinkers’ risk of cancers of the head and neck and the esophagus.

The researchers looked at the effect of gene variations in other enzymes involved in alcohol and folate metabolism but found there wasn’t enough data to fully assess the effect of those gene variants on cancer risk.

They said that currently available data does not allow for a quantitative evaluation by meta-analysis of the link between gene variations and cancer risk in people who drink alcohol.

“We have highlighted the need for large, multicenter studies and for approaches to the study of multiple polymorphisms,” wrote Dr. Nathalie Druesne-Pecollo and colleagues at the French National Institute of Agronomical Research.

The review was published in the February issue of the The Lancet Oncology.

Previous research has shown a clear link between alcohol consumption and health risk, according to background information in the review. Recent figures show that drinking alcohol was a major contributing factor in the development of almost 400,000 cancers worldwide in 2002. In that same year, 323,900 cancer deaths (3.6 percent of all cancer deaths) were alcohol-related.

Source:
The Lancet Oncology, news release, Jan. 30, 2009

February, 2009|Oral Cancer News|

HPV testing followed by cytology and repeat HPV testing may improve cervical cancer screening

Source: JNCI Journal of the National Cancer Institute 2009 101(2):69
Author: staff

The use of human papillomavirus (HPV) DNA testing as an initial screening step followed by triage with a standard Pap test (cytology) and repeat HPV DNA testing may increase the accuracy of cervical cancer screening, according to a study in the Jan. 13 online issue of the Journal of the National Cancer Institute. Compared to cytology alone, the screening strategy improved detection of precancerous growths without a substantial increase in the number of false-positive tests.

Randomized trials have shown that using DNA testing for HPV—which is known to cause cervical cancer—in screening programs would increase detection of cervical intraepithelial neoplasia (CIN) compared with cytology. However, HPV DNA testing also results in a substantial increase in false-positive tests, which lead to unnecessary and costly retesting.

In the current study, Joakim Dillner, M.D. of Lund University in Malmö, Sweden, and colleagues compared the efficacy of 11 different screening strategies that used HPV DNA testing, cytology, or a combination of the two. To evaluate the different strategies the investigators retrospectively analyzed data from 6,257 women who were enrolled in the intervention arm of a large randomized screening trial, called Swedescreen, in which HPV DNA testing was used in addition to standard cytology.

As seen in previous trials, the use of HPV DNA testing in conjunction with cytology increased the screening efficacy, detecting 35 percent more cases of CIN grade 3 or worse, compared with cytology alone. The strategy, however, doubled the number of tests required. By contrast, the use of the HPV primary screen with cytology and repeat HPV testing resulted in a 30 percent higher detection rate compared to cytology alone, with only a 12 percent increase in the number of tests required. In this approach, all women with HPV infections detected on the primary screening went on to have a standard Pap test; those with normal cytology then had a repeat HPV DNA test at least 1 year later.

“In conclusion, our data indicate that using HPV DNA testing as primary screening followed by cytological triage and repeat HPV DNA testing of women with normal cytology who are HPV DNA positive after at least 1 year is a feasible strategy for incorporating HPV testing in primary cervical screening because it improves sensitivity and maintains a high [positive predictive value], thus minimizing unnecessary referrals,” the authors write.

Citation:
Naucler P, et al. Efficacy of HPV DNA Testing with Cytology Triage and/or Repeat HPV DNA Testing in Primary Cervical Cancer Screening. J Natl Cancer Inst 2009;101: 88–99.

January, 2009|Oral Cancer News|

SensiGen HPV assay enables major breakthrough in diagnosis and treatment of head and neck cancer

Source: www.marketwatch.com
Author: press release

SensiGen LLC, a privately held biotechnology company focused on developing proprietary gene-based molecular diagnostic tests announced today a new program to make the Company’s AttoSense(TM) HPV assay available to head and neck cancer researchers worldwide after recent studies showed that the success or failure of various treatment options (chemotherapy, radiation, extensive surgery) are largely determined by the viral load of Human Papillomavirus (HPV) in tissue samples from patients.

These studies, carried out by the Head and Neck Oncology Team at the University of Michigan and published in the Journal of Clinical Oncology, demonstrate that head and neck cancer patients with higher concentrations of HPV, a virus long known to be associated with head and neck cancer, cervical cancer, and others, are much more likely to respond to organ-sparing chemotherapy than patients without high concentrations of the virus. This finding could offer significant hope for thousands of head and neck cancer patients facing uncertain and unpleasant treatments.

“The data clearly show the importance of quantitative HPV testing in patients diagnosed with head and neck cancer,” said Dr. Thomas Carey, leader of the University of Michigan based team that reported the breakthrough results this summer. “With the AttoSense(TM) HPV test and other biomarkers, we may soon be able to pinpoint the right therapy for each patient and maximize the chance of success on the first try, thus reducing the number of people who must endure multiple costly and uncomfortable treatments.”

SensiGen’s AttoSense(TM) diagnostic assays are capable of accurately identifying minute quantities — in some cases as little as a single copy — of the biomarkers that signal the onset of major diseases or the pathogens that cause them. AttoSense(TM) HPV is the only assay in the world that can quantify and determine the presence or absence of each of the 15 known cancer causing forms of HPV, as well as calculate the relative “load” of the virus, all in a single, automated step.

“The AttoSense(TM) HPV test is the only assay that can reliably determine viral load for each HPV type at the 65 copies per cell threshold established by Carey et al.,” said Dr. Jay Stoerker, Vice President of Research and Development at SensiGen. “We currently support many such research studies worldwide in the area of cervical cancer, where HPV DNA testing is well established, but after the Michigan team’s breakthrough findings, we decided to launch a new program specifically for head and neck cancer research to bring the promise of the AttoSense(TM) technology to benefit the thousands of patients suffering from this disease.”
SensiGen’s new program will support head and neck cancer studies worldwide by providing education and training on the AttoSense(TM) technology and its application in HPV to research professionals and clinical investigators worldwide SensiGen is also discussing partnerships with independent reference laboratories to offer the AttoSense(TM) HPV test more broadly around the world.
“Since the results of Dr. Carey’s studies were published, interest in the AttoSense(TM) HPV test has been running high,” explained Shawn M. Marcell, President and CEO of SensiGen. “This is another example of an advanced molecular diagnostic test linking directly to targeted therapy, with enormous benefits not only in terms of better health care and reduced patient suffering, but reduced costs as well. We decided it was important to set up a formal program to meet the demands of the market and demonstrate this value.”

AttoSense(TM) HPV test kits are available for research use only (RUO). Parties interested in supporting or participating in the SensiGen head and neck cancer research program should contact the Company at 734-213-7600 or info@sensigen.com.

About Head and Neck Cancer
Head and Neck cancers, which include oral cancer, cancers of the larynx and pharynx and others, account for about 3 to 5 percent of all cancers. In the US, about 40,000 new cases of head and neck cancer are diagnosed each year. The use of tobacco products, particularly “chew” or “snuff” products are highly associated with increased risk of head and neck cancer, along with other factors including alcohol use and HPV infection. Treatment options include chemotherapy, radiation therapy, and radical surgery. Many of the organs and tissues in the head and neck, such as the larynx and the pharynx, are in locations that are difficult to access for targeting radiation, applying chemotherapy, or conducting surgery, and hence, treatments for these conditions tend to damage adjacent tissues and cause increased patient suffering. Many patients are given a series of treatments before achieving desired results.
The AttoSense(TM) HPV test is a highly sensitive (98%+) and specific (99%+) multiplex assay that identifies the presence and quantity of all known oncogenic types of HPV in one step. The extreme accuracy versus conventional methods, attractive customer economics, and seamless fit with current laboratory practice offered by the AttoSense(TM) HPV Test are unmatched by any current or known methods. This assay is currently available for research use, and clinical trials are expected to begin in late 2008.

About SensiGen LLC
SensiGen is a biotechnology company focused on gene-based molecular diagnostics. The Company develops advanced high value diagnostic tests to enable early detection of diseases, aimed at improving standards of care and reducing overall health care costs. Current products in development include tests for early detection of human papillomavirus (HPV), the primary cause of cervical cancer, chronic kidney disease (CKD), Crohn’s disease, Lupus, and others. SensiGen’s proprietary molecular diagnostic assays offer dramatic improvements over current methods. www.sensigen.com

September, 2008|Oral Cancer News|