Research could lead to new biomarkers for clinical laboratory tests that spot disease early in patients
As we have covered in previous Dark Daily ebriefs, there are ongoing efforts to develop diagnostic assays that use human breath as the specimen. One early example was the breath specimen for Helicobacter pylori (H. pylori) testing—the bacteria that causes peptic ulcers—in the 1990s. Thus, a new sensor developed by scientists at Zhejiang University in China that can detect the presence of lung cancer in human breath will be of interest to medical laboratory scientists and clinical laboratories working on such testing.
In a proof-of-concept study, the Zhejiang University researchers “developed ultrasensitive nanoscale sensors that in small-scale tests distinguished a key change in the chemistry of the breath of people with lung cancer,” according to an American Chemical Society (ACS) news release.
The new research exemplifies how instruments are becoming increasingly sensitive to detection of smaller specimen quantities, making it possible to even use exhaled breath to diagnose lung cancer, noted a review article published in Science Direct.
“This study presents a novel Pt@InNiOx [platinum (Pt), indium (In), nickel (Ni)] nanoflake isoprene sensor that achieves an exceptionally low limit of detection at two parts per billion (2ppb)—the lowest reported for isoprene sensor to date,” wrote study lead author, Pingwei Liu, PhD (above), distinguished research fellow, Zhejiang University, et al, in ACS Sensors. “Our work not only provides a breakthrough in low-cost, noninvasive cancer screening through breath analysis but also advances the rational design of cutting-edge gas sensing materials.” Clinical laboratories working with breath sample biomarkers will be intrigued by this new advancement in the technology. (Photo copyright: Zhejiang University.)
Finding the Breakthrough Sensor
The Zhejiang University researchers were motivated by the potential for rapid gas sensing in diagnostics. Many gases, including carbon dioxide, are exhaled. But one particular gas, isoprene, they found “can indicate the presence of lung cancer,” the news release states.
However, while breath is readily available, it is not easy to isolate breath biomarkers. That is because a detector needs to “differentiate between volatile chemicals, withstand the natural humidity of exhaled breath, and detect tiny quantities of specific chemicals,” New Atlas explained.
To detect small specimen quantities of isoprene, a highly sensitive sensor needed to be developed—one that would be a step up from standard indium oxide-based breath sensors.
The scientists experimented with a series of indium (III) oxide (In203)-based nanoflake sensors until they found the sensor that performed consistently in nine experiments. They called it Pt@InNiOx for the platinum (Pt), indium (In), and nickel (Ni) it contained.
According to the news release, the Pt@InNiOx sensor:
Had “sensitivity that far surpassed earlier sensors” as evidenced by detection of isoprene as low as 2ppb.
Emphasized isoprene attraction over other volatile compounds in breath.
Has advanced sensitivity due to “Pt nanoclusters uniformly anchored on the nanoflakes” activating the isoprene sensing.
Gadget Review described the innovation as a “significant advance in diagnostic capability” that uses nanoscale technology along with “indium oxide nanoflakes with platinum-based nanoclusters.”
Developing the Lung Cancer Diagnostic Device
The scientists put their Pt@InNiOx nanoflakes into a portable sensing device for breath analysis. They then inserted breath samples from 13 people including five who had lung cancer. They found that:
In samples from people with cancer, the device enabled detection of isoprene levels lower than 40 ppb.
In samples from cancer-free participants, the device found isoprene levels more than 60 ppb.
“We integrate these ultrasensitive Pt@InNiOx nanoflakes into a miniaturized portable electronic device that successfully distinguishes lung cancer patients with expiratory isoprene below 40ppb, from the healthy population with isoprene above 60 ppb, enabling an accurate diagnosis in clinics,” wrote study lead author, Pingwei Liu, PhD, distinguished research fellow, Zhejiang University, et al, in ACS Sensors.
“As the isoprene hits the nanoflakes, electron release is sparked in a way that can be measured,” MSN Health reported, adding that the nanoflakes were also able to find isoprene in other chemicals and operate even in humid conditions.
Breath as Lab Test Biomarker for Cancer
In the United States, more people die from lung cancer than any other form of cancer, according to US Centers for Disease Control and Prevention statistics. The CDC data show there were 209,500 new lung and bronchus cancer cases in 2022, the most recent year for available data.
The Zhejiang University scientists reportedly plan to continue their research on the sensing materials and link between isoprene and lung cancer.
Studies continue to show many components in human breath can be used as clinical laboratory test biomarkers. Assays that use the breath as specimen may one day play an important role in early diagnosis of lung cancer and other diseases.
Trend will likely lead to physicians ordering more clinical laboratory screening tests for cancer among all age groups, including young patients
Upticks in colorectal cancer cases among younger populations, as reported in recent news stores, is an issue that has implications for clinical laboratories. According to a study conducted at the University of Missouri-Kansas City (UMKC), the number of colorectal cancer cases in the US has increased greatly since 1999 with the “most dramatic jumps” seen in children, teens, and young adults, a Digestive Disease Week (DDW) news release reported.
“Colorectal cancer is no longer considered just a disease of the elderly population,” said lead researcher Islam Mohamed, MD, an internal medicine resident physician at UMKC. “It’s important that the public is aware of signs and symptoms of colorectal cancer.”
The researchers noted in the DDW news release that “colorectal cancer cases, over about two decades, increased by 500% among children, ages 10 to 14; 333% in teens, ages 15 to 19; and 185% among young adults, ages 20 to 24.”
“[The results of the UMKC study] means that there is a trend. We don’t know what to make of it yet. It could be lifestyle factors or genetics, but there is a trend,” lead researcher Islam Mohamed, MD (above), Internal Medicine Resident, University of Missouri-Kansas City, told NBC News. If proved, this trend could lead to increased demand for clinical laboratory screening tests for colorectal and other cancers among young people. (Photo copyright: Digestive Disease Week.)
0.6/100,000 children ages 10 to 14 (a 500% increase).
1.3/100,000 teens ages 15 to 19 (a 333% increase).
Two/100,000 young adults ages 20 to 24 (a 185% increase).
Albeit small numbers, the cases are growing at a rate that is troublesome, according to experts. As NBC put it, “any increase can take on a larger significance” when rates begin at low points.
The study also found incidence of colorectal cancer up in people in their 30s and 40s, reaching by 2020:
6.5/100,000 people ages 30 to 34 (a 71% increase).
11.7/100,000 people ages 35 to 39 (a 58% increase).
20/100,000 people ages 40 to 44 (a 37% increase).
Screening Guidelines May Need to Change
Further research based on UMKC’s study findings could lead to changes in cancer screening guidelines.
“We were screening people from the age of 60 for colon cancer. This has now been lowered to 55, and that is due to be lowered again to 50 over the next few months,” Jude Tidbury, RN, nurse endoscopist and clinical nurse specialist, gastroenterology and endoscopy, at the UK’s East Sussex Healthcare NHS Trust, told Healthline.
In the US, the American Cancer Society advises people of average risk for cancer to start screening for colorectal cancer at age 45. The test options ACS recommends annually include:
What is behind early-onset colorectal cancer among certain age groups? An international study led by Fred Hutchinson Cancer Center (Fred Hutch), Seattle, found “strong correlations” with consuming alcohol and being obese with early-onset colorectal cancer in adults under age 50, according to a news release.
The researchers set out to explore the common genetic variants and causal modifiable risk factors that are behind early-onset colorectal cancer, according to a paper they published in the journal Annals of Oncology.
To do so they used big databases, pulling out 6,176 early-onset colorectal cancer cases and 65,829 controls from sources including:
They focused on “lifestyle factors increasing risk” by comparing the genetic variations in those with colorectal cancer to healthy people, the Fred Hutch news release explained.
“It’s important to see that alcohol and obesity are linked to early-onset colorectal cancer. Also, insulin signaling and infection-related biological pathways. These are all really important to understand—it’s helping us to develop interventions,” said Ulrike Peters, PhD, Professor and Associate Director, Public Health Services Division, Fred Hutch, who co-led the research, in the news release.
Peters noted future research may aim to address data gaps relating to racial and ethnic groups.
More Colorectal Cancer Tests
As studies continue to explore the notion that cancer may not be a disease of aging,
clinical laboratories could see more primary care physicians and healthcare consumers using colorectal cancer screening tests, which require analysis and reporting by labs.
Medical laboratory leaders may want to proactively encourage lab sales and service representatives to educate physician office staff about using the lab’s available resources for screening young adults for colorectal cancer.
Predicted steady increase in the number of new cancer cases globally will stress pathologist and clinical laboratories to process specimens and issue timely cancer diagnoses to referring physicians and patients
In many nations today, it is recognized that the demand for cancer testing services outstrips the capacity of anatomic pathology laboratories to perform cancer testing in a timely manner. Now a new report published in CA, a journal of the American Cancer Society, estimates that the number of new cancers globally will increase substantially during the next few decades.
With today’s cancer diagnostic technologies and standards of practice, it is anatomic pathologists who will typically receive biopsies or patient specimens, perform the tests, and confirm/report whether a patient has cancer. Thus, this new report projecting that the disease will grow 77% to 35 million cases by the year 2050 should be of interest to pathology groups and clinical laboratories worldwide.
The report is a collaboration between the World Health Organization’s International Agency for Research on Cancer (WHO/IARC) and the American Cancer Society (ACS). The report called for “global escalation of cancer control measures” and paying close attention to risk factors such as smoking, obesity, and infections, according to an IARC statement.
Unfortunately, the news about increasing cancer cases comes at a time when worldwide demand for pathologists already far exceeds available supply.
“The impact of this increase will not be felt evenly across countries of different HDI [human development index] levels. Those who have the fewest resources to manage their cancer burdens will bear the brunt of the global cancer burden,” said epidemiology of cancer researcher Freddie Bray, PhD (above), Head of the Cancer Surveillance Branch at the IARC in Lyon, France, in a press release. Bray “specializes in estimating the global cancer burden and predicting future trends,” according to the organization’s website. He also “leads the Global Initiative for Cancer Registry Development (GICR), which is aimed at expanding the coverage and quality of population-based cancer registries in low- and middle-income countries.” Clinical laboratories and anatomic pathologists in the United States and abroad would be wise to keep an eye on the coming cancer burden. (Photo copyright: IARC.)
Top Diagnosed Cancers
To complete their study, the WHO/IARC researchers tapped GLOBOCAN [Global Cancer Observatory] estimates of cancer incidence and mortality, the disease’s geographical variability, and predictions based on global demographic projections.
The 10 most frequently diagnosed cancers for men and women (combined) by percent of cancer sites and number of new cases in 2022 include:
For women, the cancer most often diagnosed was at the breast site. It was also the leading cause of death from cancer, the CA study noted, adding that lung and colorectal cancer cases and deaths in women followed breast cancer.
For men, lung cancer was the top cancer diagnosed in terms of cases and deaths, ahead of prostate and colorectal cancer for new cases.
Geographic HDI Affects Cancer of Citizens
The geographic areas with the highest distribution of new cancer cases and mortality rates in 2022, according to the CA paper, are:
Asia: 49.2% of cases, 56.1% of deaths.
Africa: 5.9% of cases, 7.8% of deaths.
Oceania: 1.4% of cases, 0.8% of deaths.
Euro: 22.4% of cases, 20.4% of deaths.
Americas: 21.2% of cases, 14.9% of deaths.
The WHO/IARC report also associated a country’s human development index (HDI)—a measure of health, longevity, and standard of living—with the likelihood of its residents developing cancer, USA Today reported.
“From a global perspective, the risk of developing cancer tends to increase with increasing HDI level. For example, the cumulative risk of men developing cancer before age of 75 years in 2022 ranged from approximately 10% in low HDI settings to over 30% in very high HDI settings,” the researchers wrote in their CA paper.
This suggests that a lack of resources to diagnose and treat cancer can hinder response and treatment.
In a news release, the WHO pointed out examples of what it termed “striking cancer inequity by HDI.”
“Women in lower HDI countries are 50% less likely to be diagnosed with breast cancer than women in high HDI countries, yet they are at much higher risk of dying of the disease due to late diagnosis and inadequate access to quality treatment,” said medical epidemiologist Isabelle Soerjomataram, MD, PhD, Deputy Head of the Cancer Surveillance Branch, WHO/IARC, in the news release.
Additionally, lung cancer-related resources were four to seven times more likely to be offered in a high-income country than a lower-income country, the WHO noted.
“WHO’s new global survey sheds light on major inequalities and lack of financial protection for cancer around the world, with populations—especially in lower income countries—unable to access the basics of cancer care,” said Bente Mikkelsen, MD, Director of the WHO’s Department of Noncommunicable Diseases, in the news release.
Current State of Pathology Demand
Is the pathology industry prepared for a global cancer burden? Hardly.
In “Examining the Worldwide Pathologist Shortage,” Dark Daily’s sister publication The Dark Report found that demand for pathology services is growing faster than the number of pathologists available to meet that demand. This is true for the United States and most other nations. Consequently, efforts are underway to more accurately measure the number of pathologists practicing in each country. Early data support the claim of an inadequate number of pathologists.
Thus, aligning clinical laboratory and anatomic pathology resources with cancer projections is especially important in light of the WHO/IARC’s recent report which suggests the number of cancer diagnoses and different types of cancer will increase dramatically in coming years.
The data could be helpful to diagnostic leaders seeking evidence to support training of more anatomic pathologists and expansion of AP laboratories, where cancer is most often confirmed and reported.
Accurate blood-based clinical laboratory testing for cancer promises to encourage more people to undergo early screening for deadly diseases
One holy grail in diagnostics is to develop less-invasive specimen types when screening or testing for different cancers. This is the motivation behind the creation of a new assay for colorectal (colon) cancer that uses a blood sample and that could be offered by clinical laboratories. The data on this assay and its performance was featured in a recent issue of the New England Journal of Medicine(NEJM).
The company developing this new test recognized that more than 50,000 people will die in 2024 from colon cancer, according to the American Cancer Society. That’s primarily because people do not like colonoscopies even though the procedure can detect cancer in its early stages. Similarly, patients tend to find collecting their own fecal samples for colon cancer screening tests to be unpleasant.
But the clinical laboratory blood test for cancer screening developed by Guardant Health may make diagnosing the deadly disease less invasive and save lives. The test “detects 83% of people with colorectal cancer with specificity of 90%,” a company press release noted.
“Early detection could prevent more than 90% of colorectal cancer-related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer-related mortality,” the study authors wrote in the NEJM.
As noted above, this is the latest example of test developers working to develop clinical laboratory tests that are less invasive for patients, while equaling or exceeding the sensitivity and specificity of existing diagnostic assays for certain health conditions.
“I do think having a blood draw versus undergoing an invasive test will reach more people, My hope is that with more tools we can reach more people,” Barbara H. Jung, MD (above), President of the American Gastroenterological Association, told NPR. Clinical laboratory blood tests for cancer may encourage people who do not like colonoscopies to get regular screening. (Photo copyright: American Gastroenterology Association.)
Developing the Shield Blood Test
Colorectal cancer is the “third most common cancer among men and women in the US,” according to the American Gastrological Association (AGA). And yet, millions of people do not get regular screening for the disease.
To prove their Shield blood test, Guardant Health, a precision oncology company based in Redwood City, Calif., enrolled more than 20,000 patients between the ages of 45-84 from across the US in a prospective, multi-site registrational study called ECLIPSE (Evaluation of ctDNA LUNAR Assay In an Average Patient Screening Episode).
“We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions,” the study authors wrote in the NEJM.
In March, Guardant completed clinical trials of its Shield blood test for detecting colorectal cancer (CRC) in men and women. According to the company press release, the test demonstrated:
83% sensitivity in detecting individuals with CRC.
88% sensitivity in detecting pathology-confirmed Stages I-III.
Additionally, the Shield test showed sensitivity by stage of:
65% for pathology-confirmed Stage I,
55% for clinical Stage I,
100% for Stage II, and
100% for Stage III.
“The results of the study are a promising step toward developing more convenient tools to detect colorectal cancer early while it is more easily treated,” said molecular biologist and gastroenterologist William M. Grady, MD, Medical Director, Gastrointestinal Cancer Prevention Program at Fred Hutchinson Cancer Center and corresponding author of the ECLIPSE study in the press release. “The test, which has an accuracy rate for colon cancer detection similar to stool tests used for early detection of cancer, could offer an alternative for patients who may otherwise decline current screening options.”
Are Colonoscopies Still Needed?
“More than three out of four Americans who die from colorectal cancer are not up to date with their recommended screening, highlighting the need for a more convenient and less invasive screening method that can overcome barriers associated with traditional options,” Daniel Chung, MD, gastroenterologist at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School, said in the Guardant press release.
Barbara H. Jung, MD, President of the American Gastroenterological Association, says that even if Guardant’s Shield test makes it to the public the “dreaded colonoscopy” will still be needed because the procedure is used to locate and test polyps. “And when you find those you can also remove them, which in turn prevents the cancer from forming,” she told NPR.
There is hope that less invasive clinical laboratory testing will encourage more individuals to get screened for cancer earlier and regularly, and that the shift will result in a reduction in cancer rates.
“Colorectal cancer is highly treatable if caught in the early stages,” said Chris Evans, President of the Colon Cancer Coalition, in the Guardant press release.
Guardant Health’s ECLIPSE study is a prime example of the push clinical laboratory test developers are making to create user-friendly test options that make it easier for patients to follow through with regular screening for early detection of diseases. It echoes a larger effort in the medical community to think outside the box and come up with creative solutions to reach wider audiences in the name of prevention.
Lack of regular clinical laboratory screenings in this age group at least partially to blame, researchers say
While cervical cancer rates have seen a 50-year decline overall, that trend is shifting among 30- to 40 year-olds who have experienced a near 2% increase from 2012-2019. This finding comes from a 2024 American Cancer Society (ACS) report that is eyeing the timeline of the human papillomavirus (HPV) vaccines and the lack of clinical laboratory cancer screenings as possible contributors to this new trend.
Though a 2% increase is significant, the study, which was published in CA: ACancer Journal for Clinicians, titled “Cancer Statistics, 2024,” noted that these cancers were “mostly early, curable tumors,” epidemiologist Ahmedin Jemal DVM, PhD, Senior Vice President Surveillance and Health Equity Science at ACS, and senior author of the new report, told NBC News.
To understand how the increase in cancer rates impacts this age group, consider the numbers: “About 13,800 American women are diagnosed with cervical cancer each year and 4,360 die from the disease,” NBC reported.
US vaccination programs for youths have lagged behind nations that have embraced HPV vaccination to positive results.
Australia, for example, has vaccinated a high proportion of its youth since the vaccine was first released in 2006. In 2023, the nation created its National Strategy for the Elimination of Cervical Cancer in Australia program and expects cervical cancer to be fully eliminated there by 2035.
For lab professionals, this demonstrates how new technologies like the HPV test and vaccine can alter how individuals are screened for diseases, and how vaccines can reduce and even eliminate diseases that were once common.
“We need to make sure we are not forgetting about that generation that was a little too old for HPV vaccination,” Jennifer Spencer, PhD (above), Assistant Professor, Department of Population Health and Department Internal Medicine, Dell Medical School, University of Texas at Austin, told NBC News. “The onus is on the healthcare system to think about who is slipping through the cracks,” she added. Lack of clinical laboratory screenings among the 30-40 age group may be contributing to the increase in cervical cancer rates. (Photo copyright: Dell Medical School.)
Lack of Clinical Laboratory Screenings
Research points to a lag in cervical cancer screenings as a possible cause for the recent rise in cases. Timely screening allows doctors to both identify and remove any worrisome lesions before they become cancerous, Jennifer Spencer, PhD, Assistant Professor of the Department of Population Health, Dell Medical School, University of Texas at Austin, told NBC News.
Screenings for women ages 21-65 have fallen 15% since 2000, according to data from the National Cancer Institute. Also, more than half of women with cervical cancer have “either never been screened or haven’t been screened in the past five years, according to the Centers for Disease Control and Prevention,” NBC reported.
The US Preventative Services Task Force recommends that women 21-29 years of age should receive Pap smears every three years. Women 30-65 years of age should do the same, or every five years with an HPV test or combo test.
Despite a decrease in cervical cancer, 29% of women in their 20s are overdue to get screening, NBC noted. This was the age group most likely to be lagging on getting screened. Spencer says that this delay in screening could explain the resulting increase in cervical cancer among the 30-40 age group.
Causes for Lack in Screenings
Regardless of age group, women who were uninsured, in a rural area, non-white, or identifying as lesbian, bisexual, or gay were also more likely to be overdue on screenings, according to Spencer’s study.
In addition, women who just moved to the United States may have missed their screenings, thus increasing risk, epidemiologist Nicholas Wentzensen, MD, PhD, Deputy Director, Senior Investigator, and Head of the Clinical Epidemiology Unit at the National Cancer Institute, told NBCNews.
Additionally, Spencer found in her research that confusion exists by both patients and doctors on when cervical screening should take place. Some participants in her study did not have screening recommended by their doctors, while others simply did not recognize it was necessary.
“When women in one of Spencer’s studies were asked why they hadn’t been screened recently, they commonly said that they didn’t know they needed to be screened or that a health provider hadn’t recommended it. Only 1% [of] women ages 21 to 29 said they had skipped screening because they had received the HPV shot,” NBC News reported.
A 2022 Journal of American Medicine (JAMA) report also looked at screenings as a possible cause. Those researchers found that “only 73% of women with abnormal screening results received follow-up care,” NBC reported.
“If the increase (in cases) is real, it could be a result of missed screening opportunities at earlier ages, as suggested by the increase in squamous cell carcinoma and localized disease. It may also stem from a decrease in screening at younger ages,” the JAMA study authors wrote.
HPV Vaccine and Cervical Cancer Prevention
The HPV vaccine is another important area of research to be considered. Approved in 2006, HPV vaccines were beneficial because HPV “causes six types of cancer, including cervical cancer,” NBC reported.
Women in their early 20s at that time were the first generation to benefit from HPV vaccines, NBC noted. It may be that they continue to benefit in a decrease in cervical cancer among their cohort.
Countries that have emphasized HPV vaccines and stringent screenings in their cancer prevention efforts are reaping the benefits of that policy.
Though cancer screening and the HPV vaccine are important first steps women should take to prevent cervical cancer, follow-through clinical laboratory testing and diagnosis is crucial, Spencer added. This would include additional testing and treatment for any abnormal results of the cancer screening.
However, according to Spencer, “only 73% of women with abnormal screening results received follow-up care,” NBC reported.
Healthcare policymakers today are emphasizing the need for providers to identify and close gaps in care as a way to improve patient outcomes and help control the cost of care. Women who are overdue for a cervical cancer screening test—whether an HPV test or Pap smear—have this care gap. This creates an opportunity for clinical labs to add value.
Clinical laboratories could be helpful during this period by looking at patient files to note which patients are overdue for screenings and then alerting their doctors. Medical labs also could work directly with doctors to establish a program to reach out to patients. Labs would thus be adding value as well as benefitting patients.
