Can semi-automated image cytometry on induced sputum become a screening tool for lung cancer?: Evaluation of quantitative semi-automated sputum cytometry on radon- and uranium-exposed workers (2025)

Is it useful to combine sputum cytology and low-dose spiral computed tomography for early detection of lung cancer in formerly asbestos-exposed power industry workers?

Journal of Occupational Medicine and Toxicology, 2014

Background: Low-dose spiral computed tomography (LDSCT) in comparison to conventional chest X-ray proved to be a highly sensitive method of diagnosing early stage lung cancer. However, centrally located early stage lung tumours remain a diagnostic challenge. We determined the practicability and efficacy of early detection of lung cancer when combining LDSCT and sputum cytology. Methods: Of a cohort of 4446 formerly asbestos exposed power industry workers, we examined a subgroup of 187 (4.2%) high risk participants for lung cancer at least once with both LDSCT and sputum cytology. After the examination period the participants were followed-up for more than three years. Results: The examinations resulted in the diagnosis of lung cancer in 12 participants (6.4%). Six were in clinical stage I. We found 10 non-small cell lung carcinomas and one small cell lung carcinoma. Sputum specimens showed suspicious pathological findings in seven cases and in 11 cases the results of LDSCT indicated malignancies. The overall sensitivity and specificity of sputum cytology was 58.0% and 98% with positive (PPV) and negative (NPV) predictive values of 70% and 97%. For LDSCT we calculated the sensitivity and specificity of 92% and 97%. The PPV and NPV were 65% and 99% respectively. Conclusions: Our results confirmed that in surveillance programmes a combination of sputum cytology and LDSCT is well feasible and accepted by the participants. Sputum examination alone is not effective enough for the detection of lung cancer, especially at early stage. Even in well-defined risk groups highly exposed to asbestos, we cannot recommend the use of combined LDSCT and sputum cytology examinations as long as no survival benefit has been proved for the combination of both methods. For ensuring low rates of false-positive and false-negative results, programme planners must closely cooperate with experienced medical practitioners and pathologists in a well-functioning interdisciplinary network.

Histopathologic Analysis of Lung Cancer Incidence Associated with Radon Exposure among Ontario Uranium Miners

International Journal of Environmental Research and Public Health, 2018

Although radon is a well-established contributor to lung cancer mortality among uranium miners, the effects of radon decay products on different histopathologies of lung carcinoma are not well established. Using a retrospective cohort design, this study aims to examine the risks of lung cancer by histological subtypes associated with exposure to radon decay products among the Ontario Uranium Miners cohort. Cases were stratified by histological groups, and associated risks were estimated for cumulative radon exposure after adjustment for attained age and calendar period. Between 1969 and 2005, 1274 incident cases of primary lung cancer were identified. Of these, 1256 diagnoses (99%) contained information on histology. Squamous cell carcinoma was most common (31%), followed by adenocarcinoma (20%), large cells (18%), small cell lung carcinoma (14%), and other or unspecified cell types (17%). Of the histological sub-groups, small cell lung carcinoma had the strongest association with c...

Clinical measures, smoking, radon exposure, and risk of lung cancer in uranium miners

Occupational and Environmental Medicine, 1996

Objectives-Exposure to the radioactive daughters of radon is associated with increased risk of lung cancer in mining populations. An investigation of incidence of lung cancer following a clinical survey of Ontario uranium miners was undertaken to explore whether risk associated with radon is modified by factors including smoking, radiographic silicosis, clinical symptoms, the results of lung function testing, and the temporal pattern of radon exposure. Methods-Miners were examined in 1974 by a respiratory questionnaire, tests of lung function, and chest radiography. A random selection of 733 (75%/6) of the original 973 participants was followed up by linkage to the Ontario Mortality and Cancer Registries. Results-Incidence of lung cancer was increased threefold. Risk of lung cancer among miners who had stopped smoking was half that of men who continued to smoke. There was no interaction between smoking and radon exposure. Men with lung function test results consistent with airways obstruction had an increased risk of lung cancer, even after adjustment for cigarette smoking. There was no association between radiographic silicosis and risk oflung cancer. Lung cancer was associated with exposures to radon daughters accumulated in a time window four to 14 years before diagnosis, but there was little association with exposures incurred earlier than 14 years before diagnosis. Among the men diagnosed with lung cancer, the mean and median dose rates were 2*6 working level months (WLM) a year and 1l8 WLM/year in the four to 14 year exposure window. Conclusions-Risk of lung cancer associated with radon is modified by dose and time from exposure. Risk can be substantially decreased by stopping smoking.

Advances in sputum analysis for screening and early detection of lung cancer

Cancer control : journal of the Moffitt Cancer Center

Screening for lung cancer using currently available techniques is not effective in reducing mortality from the disease. Archived sputum specimens and clinical data linking specimens to lung cancer outcomes from prior screening programs have been reexamined to evaluate altered gene expressing, including specific oncogene activation and tumor suppressor gene deletion, as well as genomic instability and abnormal methylation. Several of these tests allow determination of a molecular diagnosis of cancer years before clinical presentation. These sputum tests provide an impetus to reconsider screening for lung cancer. Prospective trials are required to confirm test performance characteristics, and management and intervention strategies must be developed that are appropriate to the stage at which lung cancer is diagnosed.

Radon Exposure, IL-6 Promoter Variants, and Lung Squamous Cell Carcinoma in Former Uranium Miners

Environmental Health Perspectives, 2015

Risk factors and early detection of lung cancer in a cohort of Chinese tin miners

Annals of Epidemiology, 1997

To examine risk factors and establish a biologic specimen and data hank fr,r tlz <trlciy ,II early markers of lung cancer. METHODS: We designed a dynamic cob ort using an ongoing lung cancer screening program ~w1011:: radon-and .lrsenic-exposed tin miners in Yunnan China. Through the first fnur years of the stuciy, ti,346 miners aged 40 years and older with over 10 years of occupational exposure have been enroiled, risk factors have been assessed, annual sputum and chest radiographs have been obtained, and numcrcw~s biologic specimens have been collected. RESULTS: A total of 243 new lung cancer case5 have been ldcntified through 1995. Radon ,+IKI arsenic exposures ate the predominant risk factors, but lung cancer risk is also associared with chrc:n~c bronchitis and silicosis, as well as a number of measures of exposure to tobacco smoke, mcluding e.lri\ age of first use. duration, and cumulative exposure. Tumor and sputum samples are being exammetl IOT early lnarkers of lung cancer. CONCLUSION: A cohort of occupationally-exposed tin miners with an extensive bi<>logtc spwimcn rcposltory has hettn successfully established to simultaneously stlldy the etioloc,ry and early Jctectioir ',i I ullg cancer.

Sputum analysis by flow cytometry; an effective platform to analyze the lung environment

PLOS ONE

Low dose computed tomography (LDCT) is the standard of care for lung cancer screening in the United States (US). LDCT has a sensitivity of 93.8% but its specificity of 73.4% leads to potentially harmful follow-up procedures in patients without lung cancer. Thus, there is a need for additional assays with high accuracy that can be used as an adjunct to LDCT to diagnose lung cancer. Sputum is a biological fluid that can be obtained non-invasively and can be dissociated to release its cellular contents, providing a snapshot of the lung environment. We obtained sputum from current and former smokers with a 30+ pack-year smoking history and who were either confirmed to have lung cancer or at high risk of developing the disease. Dissociated sputum cells were counted, viability determined, and labeled with a panel of markers to separate leukocytes from non-leukocytes. After excluding debris and dead cells, including squamous epithelial cells, we identified reproducible population signature...

Radon as a risk factor for extra-pulmonary tumours

Medical oncology and tumor pharmacotherapy, 1993

Exposure to radon in uranium and other mines is a well recognised risk factor for lung cancer. There is also increasing evidence of a risk of lung cancer from indoor radon. An excess of stomach cancer has been observed in some mining populations but the role of radon is unclear. A few correlation studies and a case-control study have indicated that exposure to indoor radon could be of some importance as a cause of other tumours, especially acute myeloid leukaemia, melanoma and kidney cancer. Also prostate cancer and some other cancer types have correlated with estimated radon exposure but the relatively few studies are not quite consistent with each other. Nevertheless, the various observations of extra-pulmonary tumours associated with radon exposure may warrant further studies, especially with regard to childhood exposure and cancers.

Automated detection of genetic abnormalities combined with cytology in sputum is a sensitive predictor of lung cancer

Modern Pathology, 2008

Detection of lung cancer by sputum cytology has low sensitivity but is noninvasive and, if improved, could be a powerful tool for early lung cancer detection. To evaluate whether the accuracy of diagnosing lung cancer by evaluating sputa for cytologic atypia and genetic abnormalities is greater than that of conventional cytology alone, automated scoring of genetic abnormalities for 3p22.1 and 10q22.3 (SP-A) by fluorescence in situ hybridization (FISH) and conventional cytology was done on sputa from 35 subjects with lung cancer, 25 high-risk smokers, and 6 healthy control subjects. Multivariate analysis was performed to select variables that most accurately predicted lung cancer. A model of probability for the presence of lung cancer was derived for each subject. Cells exfoliated from patients with lung cancer contained genetic aberrations and cytologic atypias at significantly higher levels than in those from control subjects. When combined with cytologic atypia, a model of risk for lung cancer was derived that had 74% sensitivity and 82% specificity to predict the presence of lung cancer, whereas conventional cytology achieved only 37% sensitivity and 87% specificity. For diagnosing lung cancer in sputum, a combination of molecular and cytologic variables was superior to using conventional cytology alone.

Lung cancer mortality in the European uranium miners cohorts analyzed with a biologically based model taking into account radon measurement error

Radiation and Environmental Biophysics, 2012

The biologically based two-stage clonal expansion (TSCE) model is used to analyze lung cancer mortality of European miners from the Czech Republic, France, and Germany. All three cohorts indicate a highly significant action of exposure to radon and its progeny on promotion. The action on initiation is not significant in the French cohort. An action on transformation was tested but not found significant. In a pooled analysis, the results based on the French and German datasets do not differ significantly in any of the used parameters. For the Czech dataset, only lag time and two parameters that determine the clonal expansion without exposure and with low exposure rates (promotion) are consistent with the other studies. For low exposure rates, the resulting relative risks are quite similar. Exposure estimates for each calendar year are used. A model for random errors in each of these yearly exposures is presented. Depending on the used technique of exposure estimate, Berkson and classical errors are used. The consequences for the model parameters are calculated and found to be mostly of minor importance, except that the large difference in the exposure-induced initiation between the studies is decreased substantially.