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.
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.
“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 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.”
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.
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.
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.
“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.
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.
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.
