"We found that nearly half of the 75 women who had been called HPV-negative by the HC2 test had detectable levels of HPV DNA by the PCR-MS method," said Divya Patel, PhD, MPH, of the University of Michigan, one of the study investigators, and lead author of the recently published paper. "More importantly, because the PCR-MS method also measures the quantity of HPV relative to the number of human cells in the sample, or 'viral load,' we determined that about 15% of these samples had HPV loads comparable to the HPV loads found in women called HPV-positive by the HC2 test. While further work to define clinically meaningful HPV detection thresholds is required, our results suggest that a type-specific, quantitative PCR-MS based test may be an important advance in the early detection of cervical cancer."
-- 199 cervical scrapings from women who had been routinely screened for HPV DNA using the HC2 test, the most widely used clinical HPV test, and 77 tissue samples taken from tumors in confirmed cervical cancer patients were analyzed using a prototype assay developed by the late Dr. David Kurnit at the University of Michigan (subsequently, the assay has been exclusively licensed by SEQUENOM and known as the AttoSense(TM) HPV assay).
-- Utilizing SEQUENOM's proprietary MassARRAY((R)) system that couples standard polymerase chain reaction (PCR) techniques with mass spectrometry (PCR-MS), study samples were simultaneously screened, genotyped and quantified for each of 13 HPV genotypes highly associated with cervical cancer.
-- Nearly half (46.7%) of the 75 cervical scraping samples that were negative for high-risk HPV by the HC2 test were positive by PCR-MS, and approximately 15% of these samples contained a higher viral load than the clinically validated cut-off of the HC2 test.
-- Eighteen (14.5%) of 124 cervical scraping samples that were positive by HC2 for high-risk HPV were negative by PCR-MS. In all these cases, degenerate DNA sequencing failed to detect any of the 13 high-risk HPV types included in the HC2 test, reflecting false positive results in the HC2 test.
"This is another example of how the precision of PCR-MS can be applied to solve important medical and scientific problems," said Charles Cantor, PhD, chief scientific officer of SEQUENOM. "Showing exceptional analytical performance in a proof-of-concept study is a significant step in designing an assay with great clinical performance. The hybridization techniques used today, simply cannot match the state-of-the-art analytical performance found with PCR-MS.
"We are very excited about the future prospects for the AttoSense HPV test, particularly the potential to close the last major gap in screening for cervical cancer and thus possibly saving thousands of lives," Dr. Cantor continued. "We are moving forward to utilize the capabilities of our MassARRAY platform to improve this test further, as having an assay that shows great standalone potential as well as the possibility of combining with other tests for HPV could play a key role in HPV genotyping. We believe that the AttoSense HPV test could be an important addition to our growing women's health portfolio and is another example of our commitment to improving the health of women around the world."
In the US alone, over 55 million women are screened each year for cervical cancer at a cost of more than $2 billion. If detected early, available treatments are extremely effective in preventing the onset of cervical cancer. For more than 60 years, the well known "Pap smear" was the primary method for detecting early signs of cervical cancer. While this test has dramatically reduced the incidence of cervical cancer over the years, it typically misses about 10-20% of cases that should be further evaluated.
Physicians have long known that HPV infection in the cervix is associated with nearly 100% of cervical cancers. A decade ago, the first test for HPV DNA, the HC2 test, was approved by the FDA to be used along with the Pap smear to better identify patients at risk for cervical cancer. Today, more than 10 million HPV DNA tests are conducted annually, and the total number of HPV DNA tests is growing at a rate exceeding 35% per year. Many have predicted a HPV DNA test capable of genotyping and quantifying HPV DNA will one day supplant the Pap smear as the primary screening test for cervical cancer. Yet, although HPV DNA tests have further reduced the incidence of cervical cancer in the US, there are still approximately 9,000 new cases and 4,000 deaths from cervical cancer each year.
The AttoSense HPV assay detects, identifies, and quantifies each of 15 HPV types associated with cervical cancer in a single reaction. Preliminary research studies show that the test can measure and reproducibly detect as few as 50 DNA copies for each of the 15 HPV genotypes in liquid cytology samples from cervical smears and tissue biopsy samples. The AttoSense test is currently available for Research Use Only. SEQUENOM intends to seek FDA and EU approvals as soon as practical. SEQUENOM will continue to collaborate with major medical centers to further validate and demonstrate the performance and value of the AttoSense HPV test.
SEQUENOM's proprietary MassARRAY system is a high performance matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry-based nucleic acid analysis platform that quantitatively measures genetic target material and its variations in a rapid, accurate, and cost efficient manner. SEQUENOM's MassARRAY system facilitates a number of nucleic acid analysis applications including single nucleotide polymorphism (SNP) genotyping and allelotyping, copy number variation analysis, quantitative gene expression analysis, quantitative methylation marker analysis, comparative sequence analysis of haploid organisms, SNP discovery, and oligonucleotide quality control.
SEQUENOM is a life sciences company committed to providing the best genetic analysis products that translate the results of genomic science into solutions for molecular diagnostics, biomedical research, translational research and molecular medicine applications. As an industry innovator in DNA detection technology, SEQUENOM's MassARRAY system allows a direct mass measurement of nucleic acids, providing unparalleled precision and quantification. On the diagnostics front, SEQUENOM is developing a comprehensive portfolio of prenatal test methods by combining the versatility of the MassARRAY system with the company's SEQureDx(TM) technology, which enables the detection of circulating cell-free fetal nucleic acids in a maternal blood sample. The company is also developing tests for oncology, infectious diseases and other disorders. The company was founded in 1994 and is headquartered in San Diego, California.
SEQUENOM((R)), AttoSense(TM), SEQureDx(TM), and MassARRAY((R)) are trademarks of SEQUENOM, Inc. All other trademarks and service marks are the property of their respective owners.
Additional investigators: Yang-Jen Shih, Duane W. Newton, Claire W. Michael, Paul A. Oeth, Michael D. Kane, Anthony W. Opipari, Mack T. Ruffin, IV, Linda M. Kalikin, and David M. Kurnit.
This work was supported in part by grants from the Mary Kay Ash Charitable Foundation (DMK), SensiGen, LLC (DMK), and the National Cancer Institute of the National Institutes of Health [K24 CA080846 (MTR), K07 CA120040 (DAP)].
Except for the historical information contained herein, the matters set forth in this press release, including statements regarding potential false negatives and such potential false negatives leading to cervical cancer, publication of the study in the September 2009 edition of Journal of Virological Methods, further work to define clinically meaningful HPV detection thresholds, the suggestion that a type specific quantitative PCR-MS based test may be an important advance in the early detection of cervical cancer, the future prospects and potential of the AttoSense HPV test, improvements to the test, the potential of the AttoSense HPV test and combining it with other tests and its role in HPV genotyping, the Company's growing women's health portfolio and the addition of the test to that portfolio, whether a HPV DNA test capable of genotyping and quantifying HPV DNA will one day supplant the Pap smear as the primary screening test for cervical cancer, the Company's intentions to seek FDA and EU approval for the test as soon as practical, the Company's plans to continue to collaborate with major medical centers to further validate and demonstrate the performance and value of the test, and the Company's ability to develop prenatal tests and tests for oncology, infectious diseases and other disorders, are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially, including the risks and uncertainties associated with the Company's ability to develop and commercialize new technologies and products, particularly new technologies such as HPV DNA diagnostics and laboratory developed tests, reliance upon the collaborative efforts of other parties, the Company's ability to manage its existing cash resources or raise additional cash resources, competition, intellectual property protection and intellectual property rights of others, government regulation particularly with respect to diagnostic products and laboratory developed tests, obtaining or maintaining regulatory approvals, and other risks detailed from time to time in the Company's Annual Report on Form 10-K for the year ended December 31, 2008 and periodic reports and other documents subsequently filed with or furnished to the Securities and Exchange Commission. These forward-looking statements are based on current information that may change and you are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement, and the Company undertakes no obligation to revise or update any forward-looking statement to reflect events or circumstances after the issuance of this press release.