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Clinical Laboratories and Pathology Groups

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Iranian Study Shows Staggering Carcinogenic Risk in Hospital Laboratories from Occupational Exposure to Deadly Chemicals

Study found highest incidences of occupational carcinogenesis among clinical laboratory and histology technicians, followed by pathologists

It has been known for years that formalin (a form of formaldehyde used as a disinfectant and preservative in the handling of tissues samples in anatomy, pathology, and microbiology labs), as well as xylene and toluene, are dangerous to clinical laboratory workers. Nations around the world have taken steps to minimize exposure to these dangerous chemicals. However, a recent study in Iran found that those measures may not have gone far enough to protect histology and clinical laboratory technicians, pathologists, and medical laboratory scientists.

The study conducted by researchers in the Department of Occupational Health Engineering, School of Public Health, at Tehran University of Medical Sciences, showed that levels of exposure to these chemicals is still significantly higher than recommended, resulting in a higher risk for cancer among lab workers in Iran’s hospitals.

The scientists published their findings in the journal Nature Scientific Reports titled, “Occupational Exposure, Carcinogenic and Non-Carcinogenic Risk Assessment of Formaldehyde in the Pathology Labs of Hospitals in Iran.”

“Employing risk assessment techniques as a complementary tool in monitoring programs for respiratory exposure in the different work setting should be considered to protect the staffs against both non-cancerous and cancer-related hazards,” the study authors wrote.

Lessons learned from the Iranian hospital lab study could benefit clinical laboratory workers in US hospitals and help those who work with formaldehyde, toluene, and xylene worldwide to reduce their chances of developing a vascular condition known as Raynaud’s phenomenon (shown above) which can lead to necrosis and gangrene, as well as other dangerous health conditions affecting the lungs, brain, and other systems and organs in the body. (Photo copyright: Wikipedia.)

Study Details

The Iranian study considered the carcinogenic and non-carcinogenic impact of occupational exposure to formaldehyde in the pathology laboratories of four Tehran hospitals. The researchers “used a quantitative risk assessment method proposed by the United States Environmental Protection Agency (EPA), along with its provided database known as the Integrated Risk Information System (IRIS). Respiratory symptoms were assessed using the American Thoracic Society (ATS) questionnaire,” the study authors wrote in Nature Scientific Reports.

The scientists found that “91.23% of exposure levels in occupational groups exceed the NIOSH [National Institute for Occupational Safety and Health] standard of 0.016 ppm.” They determined that “41.03% of all the studied subjects were in the definite carcinogenic risk range (LCR > 10−4), 23.08% were in the possible carcinogenic risk range (10−5 < LCR < 10−4), and 35.90% were in the negligible risk range (LCR < 10−6),” they wrote.

“The highest index of occupational carcinogenesis was observed in the group of lab technicians with a risk number of 3.7 × 10-4, followed by pathologists with a risk number of 1.7 × 10-4,” the scientists wrote. “Furthermore, 23.08% of the studied subjects were within the permitted health risk range (HQ < 1.0), while 76.92% were within the unhealthy risk range (HQ > 1.0),” they added.

“Formaldehyde exhibits high solubility in water and is rapidly absorbed by the nasal cavity, sinuses, throat, and mucous membrane of the upper respiratory tract upon exposure,” the study authors wrote. “Consequently, due to the elevated potential for both carcinogenic and non-carcinogenic formaldehyde exposure among pathology staff—particularly laboratory technicians—the implementation of management measures … becomes imperative to lower the exposure levels of all employees below permissible limits.”

Those management measures include:

  • “Strict guideline adherence and safe work protocols,
  • “Increasing staff numbers to decrease exposure duration,
  • “Adoption of engineering solutions such as localized ventilation systems, and
  • “Use of respiratory protective equipment during sample handling and tissue processing.”

Previous Reports on Exposure Risk to Clinical Lab Workers

The knowledge of the danger behind these chemicals isn’t new.

In “National Academy of Sciences Confirms That Formaldehyde Can Cause Cancer in a Finding That Has Implications for Anatomic Pathology and Histology Laboratories,” Dark Daily covered how, in 2011, the US Department of Health and Human Services (HHS) National Toxicology Program’s (NTP) “Report on Carcinogens” was the first instance where formaldehyde was upgraded to “known to be a human carcinogen.”

In 2017, a pathology lab in Auckland, New Zealand, lost its accreditation because formaldehyde levels were so high the lab had to be evacuated nearly every day, The New Zealand Herald reported.

And in “Health of Pathology Laboratory Technicians at Risk from Common Solvents like Xylene and Toluene,” we reported on a 2011 study conducted in Wellington, New Zealand, that linked exposure to these chemicals with increased auto immune connective tissue diseases, notably doubling likelihood of developing Raynaud’s phenomenon.

“In epidemiological studies on industrial workers, pathologists and anatomists, the relationship between exposure to formaldehyde and an increased risk of various types of cancer including nasal cavity, nasopharynx, lung, brain, pancreas, prostate, colon and atopic lymphoma system has been determined,” the Iranian scientists wrote in Nature Scientific Reports.

Call for Stronger Regulations

“The Food and Drug Administration (FDA), the Consumer Product Safety Commission (CPSC), and the Environmental Protection Agency have expressed serious concern about the carcinogenicity of formaldehyde,” the Iranian scientists noted, adding that “the potential carcinogenic risk to humans has been studied in a number of cohort and case-control studies.”

There is room for more studies looking at the health effects of exposure to these chemicals among lab workers, as well as continued evaluation of the risks and preventative measures that could be taken. Perhaps tightened regulations will make its way to US labs, echoing more stringent ones of the European Union.

“It is imperative to implement control measures across various hospital departments to mitigate occupational formaldehyde exposure levels proactively. These findings can be valuable for policymakers in the health sector, aiding in the elimination or reduction of airborne formaldehyde exposure in work environments,” the Iranian scientists wrote.

Managers of histology and clinical laboratories may find useful advice in hospital laboratory studies like that coming out of Iran. Protecting the health of lab workers worldwide starts with reducing their exposure to deadly chemicals.

—Kristin Althea O’Connor

Related Information:

Occupational Exposure, Carcinogenic and Non-Carcinogenic Risk Assessment of Formaldehyde in the Pathology Labs of Hospitals in Iran

National Academy of Sciences Confirms That Formaldehyde Can Cause Cancer in a Finding That Has Implications for Anatomic Pathology and Histology Laboratories

Pathology Lab Loses Accreditation Because of High Levels of Formaldehyde

Health of Pathology Laboratory Technicians at Risk from Common Solvents like Xylene and Toluene

NTRL Report on Carcinogens. Twelfth Edition, 2011

Lancet Study Finds Urgent Need for Improvement in Clinical Laboratory Prostate Cancer Screening Worldwide

Ongoing increases in the global number of prostate cancer cases expected to motivate test developers to deliver better screening tests to pathologists and clinical lab scientists

No less an authority than the peer-reviewed healthcare journal The Lancet is drawing attention to predictions of increasing prostate cancer cases across the globe, triggering calls for the development of cheaper, faster, and more accurate assays that pathologists and medical laboratories can use to screen for—and diagnose—prostate cancer.

Swift population growth and rising life expectancy will cause the prostate cancer death rate to nearly double in the next 20 years, according to a new study that has led scientists to call for immediate, critical improvements in clinical laboratory testing for cancer screening, Financial Times (FT) reported.

The International Agency for Research on Cancer (IARC) partnered with The Lancet Commission for the study. They found the strongest need is with underserved populations.

“Low- and middle-income countries need to prepare to prevent a sharp rise in fatalities while richer nations should pay more attention to young men at higher risk of the disease,” FT noted. The study, titled, “The Lancet Commission on Prostate Cancer: Planning for the Surge in Cases,” predicts cases will jump from 1.4 million in 2020 to 2.9 million by 2040.

“Prostate cancer is the most common cancer in men in 112 countries, and accounts for 15% of cancers. In this Commission, we report projections of prostate cancer cases in 2040 on the basis of data for demographic changes worldwide and rising life expectancy. … This surge in cases cannot be prevented by lifestyle changes or public health interventions alone, and governments need to prepare strategies to deal with it,” the study authors wrote.

“The findings in this Commission provide a pathway forward for healthcare providers and funders, public health bodies, research funders, governments, and the broader patient and clinical community,” the authors noted. In their Lancet paper, the researchers define clear areas for improvement.

Given the shortage worldwide of pathologists—especially highly-trained pathologists—the gap between the demand/need for expanded prostate cancer testing as screens (along with prostate biopsies) and the available supply of pathologists will encourage companies to develop screening and diagnostic tests that are accurate and automated, thus increasing the productivity of the available pathologists.

“As more and more men around the world live to middle and old age, there will be an inevitable rise in the number of prostate cancer cases. We know this surge in cases is coming, so we need to start planning and take action now,” said Nick James, PhD (above), Professor of Prostate and Bladder Cancer Research at The Institute of Cancer Research, in a press release. Pathologists and medical laboratories worldwide will want to monitor progress of The Lancet Commission’s recommendations. (Photo copyright: Institute of Cancer Research.)

Focus on Outreach, AI, Research/Development

“The only thing you can do to mitigate the damage … is to set up programs that diagnose it earlier to allow earlier treatment,” Nick James, PhD, The Lancet Commission study’s lead author, told the Financial Times. James is Professor of Prostate and Bladder Cancer Research at The Institute of Cancer Research (IRC) and The Royal Marsden NHS Foundation Trust, London.

“Evidence-based interventions, such as improved early detection and education programs, will help to save lives and prevent ill health from prostate cancer in the years to come. This is especially true for low- and middle-income countries (LMICs) which will bear the overwhelming brunt of future cases,” he said in a press release.

Communication is key. “Improved outreach programs are needed to better inform people of the key signs to look out for and what to do next,” James N’Dow, MD, Professor and Chair in Surgery and Director of the Academic Urology Unit at the University of Aberdeen in the UK, told the Financial Times. “Implementing these in tandem with investments in cost-effective early diagnostic systems will be key to preventing deaths,” he added.

Capitalizing on artificial intelligence (AI) analysis to help translate results was another area The Lancet Commission researchers focused on, Financial Times noted.

AI could “subdivide disease into potentially valuable additional subgroups to help with treatment selection. In environments with few or no pathologists, these changes could be transformational,” the study authors wrote.

High Income Countries (HICs) would benefit from AI by empowering patients. “Linking cloud-based records to artificial intelligence systems could allow access to context-sensitive, up-to-date advice for both patients and health professionals, and could be used to drive evidence-based change in all settings,” the study authors added. Such a trend could lead to specialist prostate cancer pathologists being referred cases from around the world as digital pathology systems become faster and less expensive.

Effective treatment strategies and bolstering areas of need is also key, the study notes. “Many LMICs have urgent need for expansion of radiotherapy and surgery services,” the study authors wrote. The researchers stress the need to immediately implement expansion programs to keep up with anticipated near-future demand.

Cancer drug therapy should follow suit.

“Research and the development of risk-stratified regulatory models need to be facilitated,” the study authors noted, citing a focus on drug repurposing and dose de-escalation. “Novel clinical trial designs, such as multi-arm platforms, should be supported and expanded,” they added.

Unique Needs of LMICs, HICs

The Lancet Commission researchers’ recommendations shift depending on the financial health of a specific area. HICs are experiencing a 30-year decline in the number of deaths resulting from prostate cancer, presumably from additional testing measures and public health campaigns that may be lacking in LMICs, Financial Times reported. And as population growth soars, low-to-middle income populations “will need to be prepared for the strain the expected surge in cases will put on health resources.”

For HICs, the study dissected the limitations of prostate-specific antigen (PSA) testing. The researchers pointed out that PSA’s inaccuracies in screening symptomless patients can pinpoint “cancers that may never cause symptoms and need no treatment,” Financial Times reported.

Missing high-risk cases was also a cause for concern. “Diagnostic pathways should be modified to facilitate early detection of prostate cancer while avoiding overdiagnosis and overtreatment of trivial disease,” the study notes.

Screenings for high-risk younger men, and continuing public campaigns about prostate cancer, should be a focus for HICs, the study authors noted. “These would include people who have a family history of the disease, are of African ancestry, or carry a genetic mutation known as BRCA2,” Financial Times reported.

While the undertaking may sound intimidating—there is already such a heavy impact worldwide from prostate cancer—the researchers are optimistic of their recommendations.

“Options to improve care are already available at moderate cost. We found that late diagnosis is widespread worldwide, but especially in LMICs, where it is the norm. Early diagnosis improves prognosis and outcomes, and reduces societal and individual costs, and we recommend changes to the diagnostic pathway that can be immediately implemented,” the study authors wrote.

What Comes Next

“More research is needed among various ethnic groups to expand understanding of prostate cancer beyond the findings from studies that were largely based on data from white men,” The Lancet Commission told the Financial Times.

Astute pathologists and medical laboratories will want to monitor efforts to develop assays that are inexpensive, more accurate, and produce faster answers. Demand for these tests will be substantial—both in developed and developing nations.

—Kristin Althea O’Connor

Related Information:

Prostate Cancer Rise Sparks Call for Overhaul of Testing

The Lancet Commission on Prostate Cancer: Planning for the Surge in Cases

Lancet Commission Predicts Sharp Increase in Global Prostate Cancer Cases

The Lancet: Prostate Cancer Cases Expected to Double Worldwide Between 2020 and 2040, New Analysis Suggests

Prostate Cancer Cases Might Rise to 3 Million Globally by 2040

WHO/IARC Study Projects Increase of 77% in Global Cancer Cases by 2050, Reports 20 Million Global Cancer Cases in 2022

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.

According to the published study, titled, “Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries,” there were 20 million new cancer cases and 9.7 million cancer-related deaths in 2022.

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:            

  • Lung:                                12.4% (2.5 million cases).
  • Female breast:                  11.6% (2.3 million cases).
  • Colorectum:                       9.6% (1.9 million cases).
  • Prostate:                             7.3% (1.5 million cases).
  • Stomach:                            4.9% (968,350 cases).
  • Liver:                                 4.3% (865,269 cases).
  • Thyroid:                             4.1% (861,173 cases).
  • Cervix:                               3.3% (661,021 cases).
  • Bladder:                             3.1% (613,791 cases).
  • Non-Hodgkin lymphoma: 2.8% (553,010 cases).

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.  

—Donna Marie Pocius

Related Information:

Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

New Report on Global Cancer Burden in 2022 by World Region and Human Development Index

Global Cancer Burden Growing Amidst Mounting Need for Services

Cancer Cases Could Increase 77% as Global Population Balloons. These Types Are Most Common

Examining the Worldwide Pathologist Shortage; How Many Pathologists Are Needed in Different Countries?

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