Purdue receives $1.35 million grant to develop cervical cancer diagnostic tool

December 10, 2010

WEST LAFAYETTE, Ind. — Purdue University researchers have received a $1.35 million grant from the National Cancer Institute for developing a next-generation biological tool designed to more accurately detect early stages of cervical cancer.

A team led by Purdue professors J. Paul Robinson and Vincent Jo Davisson, whose laboratories are based at Discovery Park's Bindley Bioscience Center, will use the three-year grant to advance the effectiveness of the Pap smear, the common medical test that has been successful in reducing the mortality rate of cervical cancer since it was introduced in the 1940s.

"The Pap smear remains an effective, widely used method for early detection of precancer and cervical cancer. But it can have a false negative rate in the range of more than 30 percent for clinically significant cervical lesions," said Robinson, a Purdue professor of biomedical engineering and veterinary medicine. "And when you have a false negative for whatever reason, that time lost can be deleterious for the patient. Our goal is to reduce that negative figure, helping thousands of women get a more precise initial diagnosis as to whether they do or do not have cervical cancer."

Through the Pap smear, a tool is used to gather cells from the outer opening of the cervix of the uterus and the endocervix. The cells are examined under a microscope to detect abnormalities and potentially precancerous changes — called squamous intraepithelial lesions (SILs) or cervical intraepithelial neoplasias (CINs) — which are usually caused by the sexually transmitted human papillomaviruses (HPVs).

Robinson and his team will combine a method called flow cytometry with a molecular test for high-risk HPVs to improve the overall accuracy and specificity of detection of clinically significant lesions in cervical cytology specimens. Long term, the project goal is to apply emerging technology to develop a high-throughput, cell-based analysis that can provide more specificity to identify cervical cancer.

Robinson and Davisson say the Pap smear has saved the lives of millions of women since its acceptance. They believe their process would improve upon that diagnostic success, creating a tool for identifying precancerous cells sooner. In addition, Robinson and Davisson are working to reduce the number of false positives that result from a Pap smear and require further evaluation to rule out the possibility of advanced stages of cancer.

"More than 4 million women each year in the United States undergo additional, costly procedures because current testing lacks the specificity in analyzing high-grade lesions in patients with low-grade cytologic abnormalities," said Davisson, a Purdue professor of medicinal chemistry and molecular pharmacology. "Thousands of women bear this emotional strain of possibly having cancer, in addition to the costs that these additional medical procedures pose on our health-care system."

The NCI grant will support the research of more than a dozen scientists, engineers, staff and students at Purdue and at partner institutions at the University of Massachusetts and Stony Brook University Medical Center in New York. The Oncological Science Center in Purdue's Discovery Park also is providing support to the project.

"An exciting aspect of this project is its translational impact — a primary goal for Purdue, Discovery Park and the Bindley Bioscience Center," Robinson said. "We are taking discovery science and moving it into the clinic where we can help make a difference. We also are talking to companies that are interested in manufacturing a new device for use in this diagnosis process."

Known as the father of cervical cytology testing, Greek doctor George Papanicolaou spent years developing the Pap test before it was universally accepted in 1943 after he published the research paper "Diagnosis of Uterine Cancer by the Vaginal Smear." Today, the Pap test is the world's most widely used cancer screening method.

Before the implementation of cervical cytology testing, cervical cancer was a leading cause of cancer death in women in the United States and other industrialized nations. Since the introduction of the Pap test, cervical cancer deaths have fallen by up to 99 percent in countries where women are screened regularly. A regular program of Pap test screening, with appropriate follow-up, can reduce cervical cancer incidence by up to 80 percent.

About 4,200 women in the United States will die from cervical cancer this year, the American Cancer Society reports. Cervical cancer also remains the second-most common cancer in women, with 500,000 new cases reported each year and 250,000 deaths worldwide. Eighty percent of the deaths occur in developing countries because of the lack of widespread screening programs.

Davisson said human error in the sampling and screening process poses the biggest hurdles for the test's accuracy. The cells may not always be successfully transferred from the sampling device to the microscope slide. In other cases, a laboratory technician may fail to detect abnormal cells present on the slide, or the cells might be detected but not be accurately classified. In most cases, Davisson said, further evaluation does not identify underlying high-grade lesions in patients with low-grade cytologic abnormalities.

Although HPV testing can play a key role in assessing the severity of a patient's illness, it has limited specificity for clinically significant lesions in women under age 30 because of the high prevalence of infection in the general population, Davisson said.

Complicating the situation is that simple detection of high-risk HPVs does not predict an underlying high-grade lesion. That's because most infections spontaneously clear and do not identify clinically significant cervical lesions, said project partner Dr. Kenneth Shroyer, professor and chair of the Department of Pathology at Stony Brook University.

Through a prior $275,000 research grant from the NCI, Robinson said, the Purdue team developed a technique using high-throughput flow cytometry and cell sorting to identify and capture the rare cancerous cells in cervical specimens. In addition, a multiplexed HPV genotyping assay has been implemented to analyze the rare cells isolated in this approach. The process has been simplified for using common samples with current pathology testing protocols.

"The development of an automated approach for the detection of cervical cancer biomarkers in cervical cytology specimens holds great promise to improve the diagnostic accuracy of cervical cancer screening," Shroyer said.

The Bindley Bioscience Center, a 50,000-square-foot facility that opened to Purdue life sciences researchers in 2005, received $14.9 million in funding this spring from the National Institutes of Health to expand its cancer and life sciences research.

The 29,000-square-foot expansion, designed to establish the university's Multidisciplinary Cancer Research Facility in partnership with the Purdue Center for Cancer Research, will begin in August 2011. Completion is tentatively set for April 2013.

Writer:  Phillip Fiorini, 765-496-3133, pfiorini@purdue.edu

Sources:    J. Paul Robinson, 765-494-0757, jpr@flowcyt.cyto.purdue.edu

                    Vincent Jo Davisson, 765-418-5558, davisson@purdue.edu

                    Kenneth Shroyer, 631-444-3000, kshroyer@notes.cc.sunysb.edu