CyPath® Lung is a noninvasive test to improve the early detection of lung cancer in patients at high risk for the disease.
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Detection of cancer at its earlier stages is key to reducing cancer mortality. At an early stage, cancer is more likely to still be localized, and not spread to other parts of the body yet, which makes treatment easier and more successful. People at high risk for lung cancer are recommended for annual screening with low dose computed tomography (LDCT) to find cancer at earlier stages when it can be successfully treated.
The National Lung Cancer Screening Trial (NLCST) of more than 53,000 high-risk patients showed LDCT screening could lower mortality rates by 20% as compared to screening with traditional x-ray. It is very important for people at high risk for lung cancer to be screened annually for the disease. Early detection of lung cancer is key to increasing the survival rate of patients.
CyPath® Lung investigates the lung micro-environment by analyzing sputum, using antibody staining of cells similar to the flow cytometry analysis of blood for lymphomas and other blood-related cancers. CyPath® Lung uniquely incorporates the porphyrin TCPP to identify cancer and cancer-related populations in sputum. Test results that are provided to the physician ordering CyPath® Lung are generated using automated analysis that is completed in minutes.
CyPath® Lung testing is performed on sputum processed into a single-cell suspension labeled with the fluorescent porphyrin TCPP that preferentially binds to cancer cells and cancer-related cells. Cells are also stained with fluorescently labeled antibodies that identify hematopoietic and epithelial cells within the sputum sample. A viability dye is used to eliminate dead cells. After the sputum sample is run through the flow cytometer and the sample data is acquired, software searches for the presence of pre-defined features that distinguish individuals at high risk who have a high likelihood of lung cancer from those who do not.
This Flow Cytometric assay was developed, and its performance characteristics of Accuracy, Precision, Specificity, and Sensitivity, were determined by Precision Pathology Services Laboratory. This assay detects cell types that are indicative of the presence of lung cancer.
The analysis is based on the following features:
Failure of individual assays may occur due to problems with specimen quality or technical issues. Negative findings do not rule out the presence of an abnormality and not all positive findings are indicative of an abnormality. All findings should be correlated with patients’ clinical history and imaging. This test has not been cleared or approved by the US Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. This test is for diagnostic purposes. It should not be regarded as investigational or for research.
Precision Pathology Services Laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) as certified to perform high complexity clinical laboratory testing.
Exfoliated cells in sputum have long been of interest for lung cancer diagnosis. Traditional slide-based sputum cytology, which looks at only a fraction of the entire sputum sample, has been shown to detect lung cancer in 60% to 82% of cases.
Sputum bathes the lungs, coming into direct contact with a possible tumor that sheds cancerous and cancer-related cells, making sputum an excellent sample for cancer detection.
Sputum can be collected easily at home, either spontaneously or with assistance from a non-invasive, hand-held airway clearing device that helps people expel the sample into a collection cup.
CyPath® Lung interrogates the lung micro-environment by analyzing sputum using flow cytometry. The test acquires information about sputum using a flow cytometer that individually scans and characterizes tens of millions of cells in minutes. CyPath® Lung labels a person’s sputum sample with fluorescent antibodies that uniquely identify different cell types and a fluorescent porphyrin called TCPP that preferentially binds to cancer cells and cancer-related cells.
TCPP fluoresces a bright red color when attached to cancer cells and cancer-associated cells that are visible when the sample is run through a flow cytometer. CyPath® Lung uses automated analysis that looks for pre-set parameters that are predictive of cancer, one of which is the presence of cells that have taken up greater amounts of the TCPP porphyrin label.
A physician orders CyPath® Lung and gives the patient a sputum collection kit to take home. The kit includes one test collection cup; a pre-addressed, overnight envelope for returning the sample; a patient instruction booklet; and a small cold pack to be placed in the freezer during the three-day collection period.
Patients collect a sputum sample at home every day for three consecutive days, expelling sputum and storing the three-day sample in the same collection cup. Sputum is expelled and collected by coughing into the collection cup. The patient stores the collection cup in a refrigerator between collections.
On the third day of collection, the patient places the collection cup containing the sputum sample back into the kit box for return by overnight mail to the laboratory. The patient adds the frozen cold pack to the kit box that contains his or her sputum sample prior to sending it to the laboratory for analysis.
While widespread use of LDCT will help lower the death rate from lung cancer, the NLCST found that LDCT screening has a low positive predictive value of only 3.8%. That means that for every 100 people who were diagnosed by LDCT as positive for lung cancer, less than four of them actually had the disease. The low positive predictive value can lead to more expensive and riskier procedures to diagnose lung cancer.
People may decide not to be screened because of the anxiety, cost, and risk of a positive LDCT result that turns out to be incorrect, but screening for lung cancer is essential if we want to diagnose early-stage cancer and save lives.
A patient-friendly, non-invasive test offers significant benefits. The use of CyPath® Lung after a positive LDCT scan has the potential to increase the positive predictive value of screening and lower the number of people who would otherwise have to undergo unnecessary and invasive procedures and provide physicians with greater confidence when follow-up is necessary.
Please visit our Patient Portal regarding our CyPath® Lung Test Kit, featuring important information about CyPath® Lung, and how to collect and return your sputum sample to the laboratory:
CyPath® Lung is billed as a basic flow cytometry test.
For more information regarding billing, click here.
Current diagnostic methods for lung cancer include PET scans, bronchoscopy, and tissue biopsy. The table below compares the sensitivity and specificity of CyPath® Lung with tests and procedures currently used to diagnose lung cancer. CyPath® Lung compares favorably to these more invasive and expensive tests.
A test validation trial comparing people at high risk for lung cancer to patients with the disease resulted in CyPath® Lung specificity of 88% and sensitivity of 82%, similar to far more invasive procedures currently used to diagnose lung cancer. CyPath® Lung performed even better, with 92% sensitivity and 87% specificity, in the group of cancer and cancer-free high-risk participants who had small nodules less than 20 mm in diameter or displayed no nodules.
The high sensitivity and specificity of CyPath® Lung for smaller nodules are important because nodules between 6 mm and 20 mm can pose more difficulty with diagnosis. CyPath® Lung can provide more certainty to physicians and their patients.
| Diagnostic Method | Specificity* | Sensitivity** |
|---|---|---|
| CyPath® Lung | 88% | 82% |
| CyPath® Lung (Nodules < 20 mm) | 87% | 92% |
| Low Dose CT (LDCT) | 73.4% | 93.8% |
| FDG PET Scan | 82% | 87% |
| Bronchoscopy | 47% | 88% |
| Fine Needle Biopsy | 75.4% | 90.4% |
| Core Needle Biopsy | 88.6% | 89.1% |
* Specificity is a measure of how many times the test correctly indicates that a person who does not have the disease is negative.
** Sensitivity is a measure of how many times the test correctly indicates that a person who does have the disease is positive.
The test validation of CyPath® Lung rests on a solid scientific foundation. Porphyrins have been known for decades to specifically concentrate in many types of cancer cells and cancer-associated cells such as macrophages that are cells that clean debris from the tissues in the body. In addition, certain porphyrins are naturally fluorescent, with a distinct photon emission profile.
Early research conducted at Los Alamos National Laboratory showed 100% accuracy in distinguishing lung cancer patients from healthy individuals by labeling sputum with the synthetic porphyrin TCPP. A later sputum cytology study published in 2015 showed that certain cells in sputum from lung cancer patients labeled by the porphyrin TCPP fluoresce a bright red color that can be measured under a microscope.
In this trial, the results of which were published in 2015, study participants were classified into cancer versus high-risk cohorts with 81% accuracy.
Building on this scientific foundation, the current CyPath® Lung test still uses porphyrins but adds other markers to the analysis. In addition, the test is now performed on a flow cytometry platform which makes it possible to quickly analyze millions of cells in a single sputum sample.
A diagnostic should be tested in the population in which it will be used. In the case of lung cancer, the relevant population is people at high risk for the disease. As LDCT screening shows, it is difficult to tell the difference between someone with cancer and someone at high risk without cancer. Smoking severely damages the lungs, leading to respiratory conditions that confound analysis and can produce nodules that look like cancer on scans.
Many clinical studies of diagnostics on the market or in development compare cancer patients with healthy individuals, resulting in seemingly higher accuracy but lacking clinical relevance. The pathology of a healthy lung is very different from one with cancer, in contrast to the lungs of a high-risk individual without cancer who has endured the insult of smoking in comparison to the lungs of patients with lung cancer. The CyPath® Lung trial compared these two very similar but difficult to distinguish cohorts – those at high risk with and those without cancer – to provide meaningful results for clinical use.
Most liquid biopsies are used after a tissue biopsy has confirmed a diagnosis to identify specific gene mutations in the tumor cells. This information helps inform therapeutic choices by giving physicians the opportunity to select drugs that target the cellular pathways that are affected by the gene mutations. CyPath® Lung detects lung cancer in high-risk individuals prior to a tissue biopsy or other confirmatory tests that establish the person has lung cancer.
Some liquid biopsies seek to find cancer earlier. So far, diagnostic liquid biopsies for early lung cancer show high sensitivity and very low specificity, or vice versa. Low sensitivity means a test misses the majority of cancers for which it is testing, leading to high false negatives. Low specificity means the test misses the majority of people who do not have cancer, instead of calling them positive, leading to many unnecessary follow-up tests. CyPath® Lung is different, showing both high specificity and sensitivity in testing for lung cancer.
CyPath® Lung analyzes the lung micro-environment by looking for pre-set parameters indicative of having lung cancer. Flow cytometry, the platform used by CyPath® Lung for analysis, profiles cell populations, i.e., whole cells, to detect disease. Liquid biopsies most often analyze blood samples. Although some identify whole cells as well (so-called circulating tumor cells), most liquid biopsies look for genetic fragments of cancer cells in blood.
Sputum is much more concentrated with cancer-related cells and cancer-related material than blood, providing a better sample to analyze for lung cancer.
Sputum travels well. A three-day sample overnighted to the laboratory exhibits high viability, with on average more than 60% of cells arriving alive for processing. In comparison, blood can be especially vulnerable to handling and processing problems. DNA, RNA, and proteins tend to degrade quickly when processed inappropriately. Degradation of test targets is a particular concern when the targets are rare, as is the case with early-stage cancers.
Several companies are developing “pan-cancer” blood tests (liquid biopsies), meaning that one blood draw could be used to detect one or more of 50 cancers. This approach limits the search for specific mutations, which is especially problematic for lung cancer since lung cancer is known to be associated with many different types of mutations.
Detection of cancer at its earlier stages is key to reducing cancer mortality. At an early stage, cancer is more likely to still be localized, and not spread to other parts of the body yet, which makes treatment easier and more successful. People at high risk for lung cancer are recommended for annual screening with low dose computed tomography (LDCT) to find cancer at earlier stages when it can be successfully treated.
The National Lung Cancer Screening Trial (NLCST) of more than 53,000 high-risk patients showed LDCT screening could lower mortality rates by 20% as compared to screening with traditional x-ray. It is very important for people at high risk for lung cancer to be screened annually for the disease. Early detection of lung cancer is key to increasing the survival rate of patients.
CyPath® Lung investigates the lung micro-environment by analyzing sputum, using antibody staining of cells similar to the flow cytometry analysis of blood for lymphomas and other blood-related cancers. CyPath® Lung uniquely incorporates the porphyrin TCPP to identify cancer and cancer-related populations in sputum. Test results that are provided to the physician ordering CyPath® Lung are generated using automated analysis that is completed in minutes.
CyPath® Lung testing is performed on sputum processed into a single-cell suspension labeled with the fluorescent porphyrin TCPP that preferentially binds to cancer cells and cancer-related cells. Cells are also stained with fluorescently labeled antibodies that identify hematopoietic and epithelial cells within the sputum sample. A viability dye is used to eliminate dead cells. After the sputum sample is run through the flow cytometer and the sample data is acquired, software searches for the presence of pre-defined features that distinguish individuals at high risk who have a high likelihood of lung cancer from those who do not.
This Flow Cytometric assay was developed, and its performance characteristics of Accuracy, Precision, Specificity, and Sensitivity, were determined by Precision Pathology Services Laboratory. This assay detects cell types that are indicative of the presence of lung cancer.
The analysis is based on the following features:
Failure of individual assays may occur due to problems with specimen quality or technical issues. Negative findings do not rule out the presence of an abnormality and not all positive findings are indicative of an abnormality. All findings should be correlated with patients’ clinical history and imaging. This test has not been cleared or approved by the US Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. This test is for diagnostic purposes. It should not be regarded as investigational or for research.
Precision Pathology Services Laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) as certified to perform high complexity clinical laboratory testing.
Exfoliated cells in sputum have long been of interest for lung cancer diagnosis. Traditional slide-based sputum cytology, which looks at only a fraction of the entire sputum sample, has been shown to detect lung cancer in 60% to 82% of cases.
Sputum bathes the lungs, coming into direct contact with a possible tumor that sheds cancerous and cancer-related cells, making sputum an excellent sample for cancer detection.
Sputum can be collected easily at home, either spontaneously or with assistance from a non-invasive, hand-held airway clearing device that helps people expel the sample into a collection cup.
CyPath® Lung interrogates the lung micro-environment by analyzing sputum using flow cytometry. The test acquires information about sputum using a flow cytometer that individually scans and characterizes tens of millions of cells in minutes. CyPath® Lung labels a person’s sputum sample with fluorescent antibodies that uniquely identify different cell types and a fluorescent porphyrin called TCPP that preferentially binds to cancer cells and cancer-related cells.
TCPP fluoresces a bright red color when attached to cancer cells and cancer-associated cells that are visible when the sample is run through a flow cytometer. CyPath® Lung uses automated analysis that looks for pre-set parameters that are predictive of cancer, one of which is the presence of cells that have taken up greater amounts of the TCPP porphyrin label.
A physician orders CyPath® Lung and gives the patient a sputum collection kit to take home. The kit includes one test collection cup; a pre-addressed, overnight envelope for returning the sample; a patient instruction booklet; and a small cold pack to be placed in the freezer during the three-day collection period.
Patients collect a sputum sample at home every day for three consecutive days, expelling sputum and storing the three-day sample in the same collection cup. Sputum is expelled and collected by coughing into the collection cup. The patient stores the collection cup in a refrigerator between collections.
On the third day of collection, the patient places the collection cup containing the sputum sample back into the kit box for return by overnight mail to the laboratory. The patient adds the frozen cold pack to the kit box that contains his or her sputum sample prior to sending it to the laboratory for analysis.
While widespread use of LDCT will help lower the death rate from lung cancer, the NLCST found that LDCT screening has a low positive predictive value of only 3.8%. That means that for every 100 people who were diagnosed by LDCT as positive for lung cancer, less than four of them actually had the disease. The low positive predictive value can lead to more expensive and riskier procedures to diagnose lung cancer.
People may decide not to be screened because of the anxiety, cost, and risk of a positive LDCT result that turns out to be incorrect, but screening for lung cancer is essential if we want to diagnose early-stage cancer and save lives.
A patient-friendly, non-invasive test offers significant benefits. The use of CyPath® Lung after a positive LDCT scan has the potential to increase the positive predictive value of screening and lower the number of people who would otherwise have to undergo unnecessary and invasive procedures and provide physicians with greater confidence when follow-up is necessary.
Please visit our Patient Portal regarding our CyPath® Lung Test Kit, featuring important information about CyPath® Lung, and how to collect and return your sputum sample to the laboratory:
CyPath® Lung is a new test. Health plan coverage will vary and for some plans may be determined on a patient case basis. Some commercial plans and Medicare Advantage may require prior authorization to make a coverage determination. Payments are established by the health plan based on the payer agreement with the laboratory. “Traditional” Medicare does not prior authorize. If covered, payment will be based on the Medicare Fee Schedule.
To streamline the insurance process, Precision Pathology Laboratory Services (PPLS) and its billing service provider, APS Medical Billing, are providing benefit verification and prior authorization services. For further information, please see the PPLS Billing Questions webpage.
Please note that PPLS cannot guarantee that the health plan will cover the test or reimburse the CyPath® Lung test in part or in full. The patient may be responsible for copayments, co-insurance, or deductibles, or for the payment in full if the test is not covered.
Current diagnostic methods for lung cancer include PET scans, bronchoscopy, and tissue biopsy. The table below compares the sensitivity and specificity of CyPath® Lung with tests and procedures currently used to diagnose lung cancer. CyPath® Lung compares favorably to these more invasive and expensive tests.
A test validation trial comparing people at high risk for lung cancer to patients with the disease resulted in CyPath® Lung specificity of 88% and sensitivity of 82%, similar to far more invasive procedures currently used to diagnose lung cancer. CyPath® Lung performed even better, with 92% sensitivity and 87% specificity, in the group of cancer and cancer-free high-risk participants who had small nodules less than 20 mm in diameter or displayed no nodules.
The high sensitivity and specificity of CyPath® Lung for smaller nodules are important because nodules between 6 mm and 20 mm can pose more difficulty with diagnosis. CyPath® Lung can provide more certainty to physicians and their patients.
| Diagnostic Method | Specificity* | Sensitivity** |
|---|---|---|
| CyPath® Lung | 88% | 82% |
| CyPath® Lung (Nodules < 20 mm) | 87% | 92% |
| Low Dose CT (LDCT) | 73.4% | 93.8% |
| FDG PET Scan | 82% | 87% |
| Bronchoscopy | 47% | 88% |
| Fine Needle Biopsy | 75.4% | 90.4% |
| Core Needle Biopsy | 88.6% | 89.1% |
* Specificity is a measure of how many times the test correctly indicates that a person who does not have the disease is negative.
** Sensitivity is a measure of how many times the test correctly indicates that a person who does have the disease is positive.
A diagnostic should be tested in the population in which it will be used. In the case of lung cancer, the relevant population is people at high risk for the disease. As LDCT screening shows, it is difficult to tell the difference between someone with cancer and someone at high risk without cancer. Smoking severely damages the lungs, leading to respiratory conditions that confound analysis and can produce nodules that look like cancer on scans.
Many clinical studies of diagnostics on the market or in development compare cancer patients with healthy individuals, resulting in seemingly higher accuracy but lacking clinical relevance. The pathology of a healthy lung is very different from one with cancer, in contrast to the lungs of a high-risk individual without cancer who has endured the insult of smoking in comparison to the lungs of patients with lung cancer. The CyPath® Lung trial compared these two very similar but difficult to distinguish cohorts – those at high risk with and those without cancer – to provide meaningful results for clinical use.
Most liquid biopsies are used after a tissue biopsy has confirmed a diagnosis to identify specific gene mutations in the tumor cells. This information helps inform therapeutic choices by giving physicians the opportunity to select drugs that target the cellular pathways that are affected by the gene mutations. CyPath® Lung detects lung cancer in high-risk individuals prior to a tissue biopsy or other confirmatory tests that establish the person has lung cancer.
Some liquid biopsies seek to find cancer earlier. So far, diagnostic liquid biopsies for early lung cancer show high sensitivity and very low specificity, or vice versa. Low sensitivity means a test misses the majority of cancers for which it is testing, leading to high false negatives. Low specificity means the test misses the majority of people who do not have cancer, instead of calling them positive, leading to many unnecessary follow-up tests. CyPath® Lung is different, showing both high specificity and sensitivity in testing for lung cancer.
CyPath® Lung analyzes the lung micro-environment by looking for pre-set parameters indicative of having lung cancer. Flow cytometry, the platform used by CyPath® Lung for analysis, profiles cell populations, i.e., whole cells, to detect disease. Liquid biopsies most often analyze blood samples. Although some identify whole cells as well (so-called circulating tumor cells), most liquid biopsies look for genetic fragments of cancer cells in blood.
Sputum is much more concentrated with cancer-related cells and cancer-related material than blood, providing a better sample to analyze for lung cancer.
Sputum travels well. A three-day sample overnighted to the laboratory exhibits high viability, with on average more than 60% of cells arriving alive for processing. In comparison, blood can be especially vulnerable to handling and processing problems. DNA, RNA, and proteins tend to degrade quickly when processed inappropriately. Degradation of test targets is a particular concern when the targets are rare, as is the case with early-stage cancers.
Several companies are developing “pan-cancer” blood tests (liquid biopsies), meaning that one blood draw could be used to detect one or more of 50 cancers. This approach limits the search for specific mutations, which is especially problematic for lung cancer since lung cancer is known to be associated with many different types of mutations.
Precision Pathology Services laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) as certified to perform high complexity clinical laboratory testing.
Economic evaluation of a novel lung cancer diagnostic in a population of patients with a positive low-dose computed tomography result (Morris, et al, Journal of Health Economics and Outcomes Research, 2024)
Study evaluates the potential significant cost savings of adding CyPath® Lung, a novel diagnostic tool utilizing flow cytometry and machine learning for the early detection of lung cancer, to the standard of care for patients with positive LDCT scans with pulmonary nodules ranging from 6 to 29 mm.
Porphyrin-modified beads for use as compensation controls in flow cytometry (Bauta, et al, Journal of Visualized Experiments, 2023)
TCPP-modified compensation beads for flow cytometry allow TCPP fluorescence in sputum samples to be distinguished from other fluorescent molecules
Automated flow cytometry test distinguishes cancer from non-cancer in sputum with high sensitivity and specificity (Lemieux et al, Respiratory Research, 2023)
Test validation trial using bioAffinity’s automated flow cytometry platform (cancer N=28 / high risk N=122) results in 82% sensitivity and 88% specificity; CyPath Lung sensitivity is 92% and specificity is 87% for patients with nodules smaller than 20 mm
Quality-controlled sputum analysis by flow cytometry to analyze the lung environment (Bederka, et al, PLOS ONE, 2022)
Research confirms that bioAffinity has developed and tested a novel flow cytometry assay including quality controls that analyzes sputum in a high-throughput manner for diagnosis of lung cancer and other lung diseases (N=140)
Quality-controlled sputum analysis by flow cytometry for lung cancer detection (Grayson, et al., Journal of Visualized Experiments, 2021)
Demonstrating the method for sputum processing that can be applied to flow cytometry platforms to analyze the sample for the diagnosis of lung disease including lung cancer, COPD and asthma
Early detection of lung cancer with Meso-Tetra (4-Carboxypheyl) Porphyrin-Labeled Sputum (Patriquin, et al, Journal of Thoracic Oncology, 2015)
Clinical trial of high-risk smokers and cancer patients used microscopy-based assay to identify TCPP-labeled cells in sputum (cancer N=26 / high risk N =102) that resulted in 81% accuracy; 77.9% sensitivity, 65.7% specificity
Internal validation study with microscopy-based assay TCPP labeling of sputum in lung cancer samples
Researchers measured TCPP-labeled cells under a microscope (cancer N= 15 / healthy N=12) resulting in 100% sensitivity and 100% specificity
Blinded study to diagnose lung cancer by labeling sputum with TCPP under a microscope
Study of uranium miners (cancer N=8 / healthy N=4) labeling sputum with TCPP resulted in 100% sensitivity and 100% specificity
TCPP porphyrin localizes more than other porphyrins in cancer cells; higher uptake of TCPP in cancer cells than normal cells
Failure of individual assays may occur due to problems with specimen quality or technical issues. Negative findings do not rule out the presence of an abnormality, and not all positive findings are indicative of an abnormality. All findings should be correlated with patients’ clinical history and imaging.
This test has not been cleared or approved by the US Food and Drug Administration (FDA). The FDA has determined that such clearance or approval is not necessary. This test is for diagnostic purposes. It should not be regarded as investigational or for research.
Precision Pathology Services Laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to perform high-complexity clinical laboratory testing.
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