News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel

News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel
Sign In

Australia’s HPV Vaccination Program Could Eliminate Cervical Cancer If Its National HPV Vaccination and Screening Programs Remain on Current Pace

CDC estimates that 92% of cancers caused by HPV could be eliminated in the US if HPV vaccination recommendations in this country are followed

Medical laboratories in the United States once processed as many as 55-million Pap tests each year. However, the need for cervical cancer screening tests is diminishing. That’s primarily because the human papilloma virus (HPV) vaccination effectively eliminates new cases of cervical cancer. At least, that’s what’s happening in Australia.

When it was introduced in 2007, Australia’s nationwide publicly-funded HPV vaccination program only included girls, but was extended to boys in 2013. Today, it is being credited with helping slash the country’s cervical cancer rates.

Research published in The Lancet Public Health (Lancet) predicts cervical cancer could be eliminated in Australia by 2028 if current vaccination rates and screening programs continue. Cervical cancer would be classified as effectively eliminated once there are four or fewer new cases per 100,000 women each year. These developments will be of interests to pathologists and cytotechnologists in the United States.

“From the beginning, I think the [Australian] government successfully positioned the advent of HPV vaccination as a wonderful package that had a beneficial effect for the population,” Karen Canfell, PhD, Director, Cancer Research Division at Cancer Council New South Wales, Australia, and Adjunct Professor, University of Sydney, told the Texas Tribune. “It was celebrated for that reason, and it was a great public health success.”

In addition to high vaccination rates, the Lancet study notes that last year Australia transitioned from cytology-based cervical screening every two years for women aged 18 to 69 years, to primary HPV testing every five years for women aged 25 to 69 and exit testing for women aged 70 to 74 years.

“Large-scale clinical trials and detailed modelling suggest that primary HPV screening is more effective at detecting cervical abnormalities and preventing cervical cancer than screening with cytology at shorter intervals,” the Lancet study states.

The incidence of cervical cancer in Australia now stands at seven cases per 100,000. That’s about half the global average. The country is on pace to see cervical cancer officially considered a “rare” cancer by 2020, when rates are projected to drop to fewer than six new cases per 100,000 women.

US Cervical Cancer Rates

In Texas, meanwhile, the state’s failure to embrace HPV vaccination is being blamed for slowing potential improvements in cervical cancer rates. In 2007, Texas lawmakers rejected legislation that would have mandated girls entering sixth grade be vaccinated for HPV. The Texas Tribune reports that, in the decade that followed, vaccination rates remained stagnant with only about 40% of Texans between 13 and 17 years old having been vaccinated for HPV by 2017.

Though Texas has a similar size population as Australia, the state’s low vaccination rates have meant cervical cancer rates have shown little improvement. Statistics compiled by the federal Centers for Disease Control and Prevention (CDC) show that Texas’ age-adjusted rate of new cervical cancer cases sits at 9.2 per 100,000 women—unchanged since 2006.

Texas has the fifth highest rate of cervical cancer in the nation, according to the CDC.

Texas State Rep. Jessica Farrar, a Democrat from Houston, maintains Texas should have followed the example of Australia, which in 2007 began a publicly funded HPV vaccination program that has the country on the verge of eliminating cervical cancer by 2028. Texas rejected mandatory HPV vaccinations and now has one of the highest cervical cancer rates in the US. “This is a preventable disease, and we should and can be doing more,” she told the Texas Tribune. “Here we are 12 years later, and look where we could’ve been, but because of certain beliefs, we’re suffering from cancers that could have been avoided.” (Photo copyright: The Texas Tribune.)

Lois Ramondetta, MD, Professor of Gynecologic Oncology at MD Anderson Cancer Center in Houston, told the Texas Tribune the state ignored an opportunity that Australia seized. “[Australia] embraced the vaccine at that time, and our fear kind of began around then,” Ramondetta said. “Really, vaccination in general has just gone down the tube since then.”

CDC Study Pushes HPV Vaccination Recommendations in US

Texas is not the only state failing to capitalize on the HPV vaccine’s cancer-curing promise. The CDC recently stated in a news release announcing a recent study that 92% of cancers caused by HPV could be eliminated if HPV vaccine recommendations were followed. CDC published the study in its Morbidity and Mortality Weekly Report.

HPV is a common virus that is linked to not only cervical cancer but also cancers of the penis, head, and neck, as well as conditions like genital warts. Though the CDC recommends children get the two-dose vaccine at ages 11-12, the study findings indicate that only 51% of teens ages 11 to 17 have received the recommended doses of HPV vaccine, a 2% increase from 2017 to 2018.

“A future without HPV cancers is within reach, but urgent action is needed to improve vaccine coverage rates,” Brett Giroir, MD, Assistant Secretary for Health, US Department of Health and Human Services (HHS), stated in the CDC news release. “Increasing HPV vaccination overage to 80% has been and will continue to be a priority initiative for HHS, and we will continue to work with our governmental and private sector partners to make this a reality.”

Can Australia Eliminate Cervical Cancer?

University of Queensland Professor Ian Frazer, MD, who co-authored the Lancet Public Health study, believes Australia is on the verge not only of eliminating cervical cancer, but also eradicating the HPV virus itself.

“Because this human papillomavirus only infects humans, and the vaccine program prevents the spread of the virus, eventually we’ll get rid of it, like we did with smallpox,” Frazer told The Age.

“It’s not going to happen in my lifetime,” he added. “But it could happen in the lifetime of my kids if they go about it the right way.”

If Australia’s combination of high HPV vaccination rates and new HPV screening program succeeds in effectively eliminating cervical cancer, clinical laboratories in this country should expect stepped-up efforts to increase HPV vaccination rates in the United States. A renewed focus on reducing—and ultimately eliminating—cervical cancer, could lead to fewer or less-frequently performed Pap tests as part of cervical cancer screening protocols.

—Andrea Downing Peck

Related Information:

The Projected Timeframe Until Cervical Cancer Elimination in Australia: A Modelling Study

Years after Texas Backed Off HPV Vaccine Mandate, Cervical Cancer Rate Soars

Cervical Cancer Set to Be Eliminated from Australia in Global First

An Estimated 92% of Cancers Caused by HPV Could be Prevented by Vaccine

Morbidity and Mortality Weekly Report

University Researchers Develop Microfluidic Device That Partitions Cancer Cells According to Size in Effort to Create a Useful Liquid Biopsy Method

Could a fast, cheap, and accurate liquid biopsy diagnostic cancer test soon be available to clinical laboratories and anatomic pathology groups?

What if medical laboratories worldwide could perform a simple liquid biopsy diagnostic test that detected cancer in its various forms? Such a test, if affordable and accurate, would be a boon to histopathology and clinical pathology laboratories. Until now, though, such a test has proven to be elusive. But, researchers at the University of Illinois at Chicago (UIC) and Queensland University of Technology (QUT) in Australia think they may have such a technology in hand.

The researchers unveiled a diagnostic device that uses microfluidic technology to identify cell types in blood by their size. The device also “can isolate individual cancer cells from patient blood samples,” according to a news release.

The ability to isolate circulating tumor cells could enable clinical laboratories to perform diagnostic cancer tests on liquid biopsies and blood samples. Dark Daily reported on various studies involving liquid biopsies—an alternative to invasive and costly cancer diagnostic procedures, such as surgery and tissue biopsies—in previous e-briefings.

The new device differs from other microfluidic technologies that rely on biomarkers to attach to tumor cells (aka, affinity separation), New Atlas reported. Papautsky co-authored a research paper on their findings published in Nature: Microsystems and Nanoengineering.

“This new microfluidics chip lets us separate cancer cells from whole blood or minimally diluted blood. Our device is cheap and doesn’t require much specimen preparation or dilution, making it fast and easy-to-use,” said Ian Papautsky, PhD, Professor of Bioengineering at University of Illinois at Chicago, in the news release. He is shown above with members of the Papautsky Lab, which has been developing “microfluidic systems and point- of-care sensors for public health applications.” (Photo copyright: University of Illinois at Chicago.)

Searching for ‘Purity’

The UIC and QUT researchers were motivated by the information-rich nature of circulating tumor cells. They also saw opportunity for escalated “purity” in results, as compared to past studies.

In the paper, they acknowledged the work of other scientists who deployed microfluidic technology affinity-based methods to differentiate tumor cells in blood. Past studies (including previous work by the authors) also explored tumor cells based on size and difference from white blood cells.

“While many emerging systems have been tested using patient samples, they share a common shortcoming: their purity remains to be significantly improved. High purity is in strong demand for circulating tumor cell enumeration, molecular characterization, and functional assays with less background intervention from white blood cells,” the authors wrote in their paper.

How the Device Works

The scientists say their system leverages “size-dependent inertial migration” of cells. According to the news release:

  • Blood passes through “microchannels” formed in plastic in the device;
  • “Inertial migration and shear-induced diffusion” separate cancer cells from blood;
  • Tiny differences in size determine a cell’s attraction to a location; and
  • Cells separate to column locations as the liquid moves.

In other words, the device works as a filter sorting out, in blood samples, the circulating tumor cells based on their unique size, New Atlas explained.

93% of Cancer Cells Recovered by Device

When the researchers tested their new device:

  • Researchers placed 10 small-cell-lung cancer cells into five-milliliter samples of healthy blood;
  • The blood was then flowed through the device; and
  • 93% of the cancer cells were recovered.

“A 7.5 milliliter tube of blood, which is typical volume for a blood draw, might have 10 cancer cells and 35- to 40-billion blood cells. So, we are really looking for a needle in a haystack,” Papautsky stated in the news release.

The graphic above illustrates how, in the lab, the microfluidic device enabled the researchers to separate out cancer cells in six of the eight lung cancer samples they studied. (Graphic copyright: Ian Papautsky, PhD/University of Illinois at Chicago/New Atlas.)

“We report on a novel multi-flow microfluidic system for the separation of circulating tumor cells with high purity. The microchannel takes advantage of inertial migration of cells. The lateral migration of cells strongly depends on cell size in our microchannel, and label-free separation of circulating tumor cells from white blood cells is thus achieved without sophisticated sample predation steps and external controls required by affinity-based and active approaches,” the researchers wrote in their paper.

The device could one day aid physicians in precision medicine and the development of targeted treatment plans for patients, reported Genetic Engineering and Biotechnology News.

Other Microfluidic Diagnostic Devices

The researchers plan wider trials and the addition of biomarkers to enable cancer DNA detection, New Atlas reported, which described the UIC/QUT study as part of a “new wave of diagnostics.”

Another novel liquid biopsy approach to cancer detection is under development at the University of Queensland. It involves a unique nano-scale DNA signature that appeared in breast cancer and other cancer studies. (See, “University of Queensland Researches May Have Found a Universal Biomarker That Identifies Cancer in Various Human Cells in Just 10 Minutes!Dark Daily, May 20, 2019.)

And researchers developed a “labyrinth” label-free microfluidic device that enabled white blood cells and circulating tumor cells to separate during a study at the University of Michigan. (See, “University of Michigan Researchers Use ‘Labyrinth’ Chip Design in Clinical Trial to Capture Circulating Tumor Cells of Different Cancer Types,” Dark Daily, February 2, 2018.)

With so much focus on liquid biopsy research, it may be possible for medical laboratories to one day not only diagnose cancer through blood tests, but also to find the disease earlier and in a more precise way than with traditional tissue sample analysis.

—Donna Marie Pocius

Related Information:

New Microfluidic Device Can Detect Cancer Cells in Blood

Microfluidic Device Promises Cheap and Fast Detection of Cancer Cells in Blood

Isolation of Circulating Tumor Cells in Non-Small-Lung Cancer Patients Using a Multi-Flow Microfluidic Channel

Liquid Biopsies Become Cheap and Easy with New Microfluidic Device

University of Queensland Researchers May Have Found a Universal Biomarker that Identifies Cancer in Various Human Cells in Just 10 Minutes

University of Michigan Researchers Use Labyrinth Chip Design in Clinical Trial to Capture Circulating Tumor Cells of Different Cancer Types

Dark Daily: Liquid Biopsy

University of Queensland Researches May Have Found a Universal Biomarker That Identifies Cancer in Various Human Cells in Just 10 Minutes!

This research could lead to a useful liquid biopsy test that would be a powerful new tool for clinical laboratories and anatomic pathologists

Cancer researchers have long sought the Holy Grail of diagnostics—a single biomarker that can quickly detect cancer from blood or biopsied tissue. Now, researchers in Australia may have found that treasure. And the preliminary diagnostic test they have developed reportedly can return results in just 10 minutes with 90% accuracy.

In a news release, University of Queensland researchers discussed identifying a “simple signature” that was common to all forms of cancer, but which would stand out among healthy cells. This development will be of interest to both surgical pathologists and clinical laboratory managers. Many researchers looking for cancer markers in blood are using the term “liquid biopsies” to describe assays they hope to develop which would be less invasive than a tissue biopsy.

“This unique nano-scaled DNA signature appeared in every type of breast cancer we examined, and in other forms of cancer including prostate, colorectal, and lymphoma,” said Abu Sina, PhD, Postdoctoral Research Fellow at the Australian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland (UQ), in the news release.

“We designed a simple test using gold nanoparticles that instantly change color to determine if the three-dimensional nanostructures of cancer DNA are present,’ said Matt Trau, PhD, Professor of Chemistry at the University of Queensland, and Deputy Director and Co-Founder of UQ’s AIBN, in the news release.

The team’s test is preliminary, and more research is needed before it will be ready for Australia’s histopathology laboratories (anatomic pathology labs in the US). Still, UQ’s research is the latest example of how increased knowledge of DNA is making it possible for researchers to identify new biomarkers for cancer and other diseases.

“We certainly don’t know yet whether it’s the holy grail for all cancer diagnostics, but it looks really interesting as an incredibly simple universal marker of cancer, and as an accessible and inexpensive technology that doesn’t require complicated lab-based equipment like DNA sequencing,” Trau added.

Such a diagnostic test would be a boon to clinical laboratories and anatomic pathology groups involved in cancer diagnosis and the development of precision medicine treatments.

One Test, 90% Accuracy, Many Cancers

The UQ researchers published their study in the journal Nature Communications. In it, they noted that “Epigenetic reprogramming in cancer genomes creates a distinct methylation landscape encompassing clustered methylation at regulatory regions separated by large intergenic tracks of hypomethylated regions. This methylation landscape that we referred to as ‘Methylscape’ is displayed by most cancer types, thus may serve as a universal cancer biomarker.”

While methyl patterning is not new, the UQ researchers say they were the first to note the effects of methyl pattern in a particular solution—water. With the aid of transmission electron microscopy, the scientists saw DNA fragments in three-dimensional structures in the water. But they did not observe the signature in normal tissues in water.

Methylation are marks that indicate whether pieces of DNA should be read,” Dino DiCarlo, PhD, Professor in the Department of Bioengineering and Biomedical Engineering, University of California Los Angeles (UCLA) and Director of Cancer Nanotechnology at UCLA’s Jonsson Comprehensive Cancer Center, told USA Today.

“To date, most research has focused on the biological consequences of DNA Methylscape changes, whereas its impact on DNA physicochemical properties remains unexplored,” UQ scientists Matt Trau, PhD (left), Abu Sina, PhD (center), and Laura Carrascosa (right), wrote in their study. “We exploit these Methylscape differences to develop simple, highly sensitive, and selective electrochemical or colorimetric one-step assays for the detection of cancer.” (Photo copyright: University of Queensland.)

Their test averaged 90% accuracy during the testing of 200 human cancer samples. Furthermore, the researchers found the DNA structure to be the same in breast, prostate, and bowel cancers, as well as lymphomas, noted The Conversation.

“We find that DNA polymeric behavior is strongly affected by differential patterning of methylcytosine leading to fundamental differences in DNA solvation and DNA-gold affinity between cancerous and normal genomes,” the researchers wrote in NatureCommunications.“We exploit these methylscape differences to develop simple, highly sensitive, and selective electrochemical or one-step assays for detection of cancer.”

Next Steps for the “Gold Test”

“This approach represents an exciting step forward in detecting tumor DNA in blood samples and opens up the possibility of a generalized blood-based test to detect cancer, Ged Brady, PhD, Cancer Research UK Manchester Institute, told The Oxford Scientist. “Further clinical studies are required to evaluate the full clinic potential of the method.”

Researchers said the next step is a larger clinical study to explore just how fast cancer can be detected. They expressed interest in finding different cancers in body fluids and at various stages. Another opportunity they envision is to use the cancer assay with a mobile device.

DiCarlo told USA Today that such a mobile test could be helpful to clinicians needing fast answers for people in rural areas. However, he’s also concerned about false positives. “You don’t expect all tumors to have the same methylation pattern because there’s so many different ways that cancer can develop,” he told USA Today. “There are some pieces that don’t exactly align logically.”

The UQ researchers have produced an intriguing study that differs from other liquid biopsy papers covered by Dark Daily. While their test may need to be used in combination with other diagnostic tests—MRI, mammography, etc.—it has the potential to one day be used by clinical laboratories to quickly reveal diverse types of cancers.  

—Donna Marie Pocius

Related Information:

Nano-Signature Discovery Could Revolutionize Cancer Diagnosis

Epigentically Reprogrammed Methylation Landscape Drives the DNA Self-Assembly and Serves as a Universal Cancer Biomarker

One Test to Diagnose Them All: Researchers Exploit Cancers’ Unique DNA Signature

Cancer Researchers in Australia Develop Universal Blood Test

Universal 10-Minute Cancer Test in Sight

A 10-Minute, Universal Blood Test for Cancer

University of Queensland Researchers Isolate DNA and RNA with New ‘Dipstick Technology’ That May Allow Medical Laboratory Testing in Extremely Remote Locations such as Jungles

Researchers successfully isolated both plant and human RNA and DNA in the field, demonstrating the potential for their new dipstick technology to identify deadly bacteria, pathogens, and diseases in water, food, and even humans

Australian researchers at the University of Queensland (UQ) have developed an intriguing “dipstick” technology that might make it possible to use simple equipment to sequence DNA and RNA in the field. Among the potential applications that will interest clinical laboratory professionals is the ability for this technology to identify pathogens, both in humans and the environment.

Medical laboratories and anatomic pathologists are aware that gene sequencing (AKA, Nucleic Acid Sequencing) is the coming revolution in diagnostics. But the process is still costly and anchored to immovable technology that requires controlled environments and reliable resources. This promising new technology could make it simpler, cheaper, and faster to extract human DNA and RNA in settings outside a sophisticated core medical laboratory.

The UQ researchers developed technology that could affect how and where diagnostic tests for a whole range of pathogens are performed. For example, tests for bacteria such as E. coli in water supplies, pathogens in food, and diseases in humans currently are conducted in environmental and clinical laboratories. This new technology may allow such diagnostics to be done in extremely remote environments.

Isolating DNA/RNA in the Field

Jimmy Botella, PhD, Professor of Plant Biotechnology, and Michael Mason, PhD, Senior Post-doctoral researcher, both at the University of Queensland, led a team of researchers who published their findings in the journal PLOS Biology. The team developed a process they called “dipstick technology,” which allows DNA and RNA to be isolated quickly and without the use of specialized equipment.

They began by using the technology on particular plants, but soon found it could be used in many other situations.

“We found it had much broader implications as it could be used to purify DNA or RNA from human blood, viruses, fungi, and bacterial pathogens from infected plants or animals,” Botella noted in a press release.

The researchers’ objective was to investigate whether or not several different materials could be used to extract nucleic acids. “The first step in any application aiming to amplify DNA or RNA is the extraction of nucleic acids from a complex biological sample; a task traditionally requiring specialized equipment, trained technicians, and multiple liquid handling steps,” they wrote in the published study.

Holding the dipstick technology (from left) Dr. Michael Mason, Professor Jimmy Botella, and Yiping Zhou, all researchers at the University of Queensland in Brisbane, Australia. (Caption and photo copyright: University of Queensland.)

Their aim was to find a simpler process that required far less personnel and equipment. They found that cellulose-based filter paper could be used to bind nucleic acids. The filter paper, which was the control early in their investigation, even retained the nucleic acids through a purification process that removed contaminants. “We then adapted the cellulose filter to create a dipstick that can be used to purify nucleic acids from a wide range of plant, animal, and microbe samples in less than 30 seconds without the need for specialized equipment,” the researchers reported.

The team conducted its first tests on the plant species A. thaliana, a flowering plant found in Africa and Eurasia. However, wanting their dipstick technology to be useful in the field, they expanded their experiments to include various species of wheat, rice, soybean, tomato, and other plants. Citrus plants, known to be challenging, also were successfully tested.

The researchers then tested if their new technology would be useful for applications in humans, which is more complicated. HIV and hepatitis can be diagnosed using commercial kits, but those kits are not useful in many settings because the samples often require sophisticated manipulation. The researchers’ method—using cellulose paper and a one-minute wash—succeeded in amplification of the nucleic acid.

Performing Diagnostics in Hospitals, on Farms, and Even in the Jungle!

The University of Queensland’s commercialization company, UniQuest, has filed a patent application for the new technology. They are currently seeking partners to commercialize and sell the dipstick technology worldwide.

“Our dipsticks, combined with other technologies developed by our group, mean the entire diagnostic process from sample collection to final result could be easily performed in a hospital, farm, hotel room, or even a remote area such as a tropical jungle,” Botella noted in the press release.

The team conducted much of their field research on remote plantations in Papua New Guinea. They conducted tests on trees, livestock, human diseases, and to detect pathogens in food and water. “The dipstick technology makes diagnostics accessible to everyone,” Botella told Technology Networks.

Dipstick Diagnostics Not New to Point-of-Care Testing

As Modern Healthcare Executive noted, dipstick technology for various diagnostic purposes is not new, even though this particular application is, potentially, revolutionary. There are dipstick tests for everything from pregnancy to cholera. Also referred to as point-of-care testing (POCT), research and development of this technology has steadily grown, and as the UQ study shows, will likely continue.

In a paper published in Clinical Biochemistry Reviews, authors Andrew St. John, PhD, of ARC Consulting, and Christopher Price, MD, of the University of Oxford, noted, “Healthcare is changing, partly as a result of economic pressures, and also because of the general recognition that care needs to be less fragmented and more patient-centered.”

While there are certainly advantages to quick diagnostic tests that can be conducted in the field, there are some challenges, as well. Julie L. V. Shaw, PhD, Assistant Professor, Department of Pathology and Laboratory Medicine at The University of Ottawa, argues that “there are many challenges associated with POCT, mainly related to quality assurance,” in a paper she published in the journal Practical Laboratory Testing.

Technology will continue to develop and drive innovation and change in how diagnostics are performed and thus in how clinical laboratories operate. Various initiatives driving the industry toward personalized medicine and value-based care are sure to play a role, alongside new technology and other advancements.

With all of those changes, one thing remains critically important and that is the value of human understanding and innovation.

—Jillia Schlingman

Related Information:

Nucleic Acid Purification from Plants, Animals and Microbes in Under 30 Seconds

UQ Dipstick Technology Could Revolutionize Disease Diagnosis

Dipstick Technology Enables Rapid Diagnosis Anywhere

Existing and Emerging Technologies for Point-of-Care Testing

Practical Challenges Related to Point of Care Testing

The March of Technology Through the Clinical Laboratory and Beyond