Oral cancer screening outcomes in the Latin American region with special relevance to Brazil and Cuba: a systematic review.

BACKGROUND:  The Latin American region represents a hotspot for oral cancer incidence and mortality. To reduce oral cancer mortality rates, screening for early detection of subjects with suspicious or innocuous oral lesions has been promoted. A systematic review was performed to assess the outcomes of oral cancer screening in the Latin American region. MATERIAL AND METHODS:  An electronic search was conducted in eight databases and grey literature. The eligibility criteria included screening where adult participants underwent any screening test during an organized screening program. Screening programs were assessed to understand trends in oral cancer diagnosis. Rates of oral cancers diagnosed in screening programs were classified as increase, decrease, or stable based on each year assessed. RESULTS:  Following our searches, twelve studies conducted in Brazil and Cuba were included. The screening tests reported were visual oral examination (VOE) and in one study in addition light-based fluorescence testing. 13,277,608 individuals were screened and a total of 1,516 oral cancers were detected (0.01%). Only two studies aimed to screen high-risk individuals (smokers and drinkers). Oral cancer cases diagnosed during screening programs were proportionately stable over the years 1997 to 2009 but increased from 2010 to 2021. The fluorescence-associated VOE test demonstrated a sensitivity of 100% and a specificity of 90%. Similarly, the VOE test alone exhibited a sensitivity of 100%, with specificity ranging from 75% to 90%. CONCLUSIONS:  Screening studies conducted in Latin American countries had serious limitations both in methodology (lack of examiner training) and in reporting data (lack of description of clinical categories of screen positives). Capacitation of health workers to perform VOE in well-designed screening programs should be implemented.

Radiation-related superficial oral mucoceles: An under-recognized acute toxicity in head and neck cancer patients.

BACKGROUND: Acute toxicity is usually defined as adverse changes occurring immediately or a short time after the start of oncological treatment. MATERIAL AND METHODS: Cross-sectional retrospective study performed with head and neck cancer patients who underwent radiotherapy from 2013 to 2016. RESULTS: Ten (1.2%) patients developed SOMs during radiotherapy, most (80%) of which were men with a mean age of 59.5 years at diagnosis. SOMs mainly affected the floor of the mouth (60%) between the fourth and the sixth weeks of radiation therapy. All lesions were asymptomatic and spontaneously ruptured approximately 9 days after diagnosis. CONCLUSIONS: Although rare, SOMs may be regarded as an acute oral toxicity of head and neck radiotherapy.

Alcohol and cigarette consumption predict mortality in patients with head and neck cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.

BACKGROUND: This study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC. PATIENTS AND METHODS: We conducted a pooled analysis, including 4759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis. RESULTS: Five-year OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined: 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR = 2.54, 95% CI 1.01-6.38, for high school or lower versus college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR = 1.73, 95% CI 1.16-2.58) and HNC-specific survival (current drinkers HR = 2.11, 95% CI 1.22-3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity (>20 cigarettes/day HR = 1.41, 95% CI 1.03-1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity. CONCLUSIONS: OS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, whereas pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low educational level is an unfavourable prognostic factor for OS in laryngeal cancer patients.

Uncommon oral manifestation of lichen sclerosus: critical analysis of cases reported from 1957 to 2016.

BACKGROUND: Lichen sclerosus is a mucocutaneous autoimmune disease which might be initiated by infectious pathogens as Borrelia Bugrdorferi and HPV. This disease shows destructive potential and is rarely diagnosed in oral mucosa. The purpose of this paper is to evaluate the characteristics of cases described in literature from 1957 to 2016, looking to provide valuable evidence about clinicopathologic features of this disease. MATERIAL AND METHODS: A MedLine search was performed aiming to find oral lichen sclerosus cases in literature and discuss its demographical and pathological characteristics as well as treatment methods performed for these cases. RESULTS: 34 oral lichen sclerosus cases with histological confirmation and one clinicopathologic study linked with this disease were found in literature. Oral lichen sclerosus affected most commonly female patients, were asymptomatic and not associated to skin or genital lesions. Furthermore, affected patients in a range of 7 - 70-years old (Average age = 31.81). CONCLUSIONS: Oral lichen sclerosus is a rare pathologic process with slight predilection for prepubertal girls, for which topical corticosterois have demonstrated satisfactory therapeutic value.

Role of medical history and medication use in the aetiology of upper aerodigestive tract cancers in Europe: the ARCAGE study.

BACKGROUND: The study aimed to investigate the role of medical history (skin warts, Candida albicans, herpetic lesions, heartburn, regurgitation) and medication use (for heartburn; for regurgitation; aspirin) in the aetiology of upper aerodigestive tract (UADT) cancer. METHODS: A multicentre (10 European countries) case-control study [Alcohol-Related CAncers and GEnetic susceptibility (ARCAGE) project]. RESULTS: There were 1779 cases of UADT cancer and 1993 controls. History of warts or C. albicans infection was associated with a reduced risk [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.68-0.94 and OR 0.73, 95% CI 0.60-0.89, respectively] but there was no association with herpetic lesions, heartburn, regurgitation or medication for related symptoms. Regurgitation was associated with an increased risk for cancer of the oesophagus (OR 1.47, 95% CI 0.98-2.21). Regular aspirin use was not associated with risk of UADT cancer overall but was associated with a reduced risk for cancer of oesophagus (OR 0.51, 95% CI 0.28-0.96), hypopharynx (OR 0.53, 95% CI 0.28-1.02) and larynx (OR 0.74, 95% CI 0.54-1.01). CONCLUSIONS: A history of some infections appears to be a marker for decreased risk of UADT cancer. The role of medical history and medication use varied by UADT subsites with aspirin use associated with a decreased risk of oesophageal cancer and suggestive of a decreased risk of hypopharyngeal and laryngeal cancers.

The relationship between ambient particulate matter and respiratory mortality: a multi-city study in Italy.

The association of air pollutants with natural and respiratory mortality has been consistently reported. However, several aspects of the relationship between particulate matter with a 50% cut-off aerodynamic diameter of 10 µm (PM(10)) and respiratory mortality require further investigation. The aim of the present study was to assess the PM(10)-respiratory mortality association in Italy and examine potentially susceptible groups. All deaths from natural (n=276,205) and respiratory (n=19,629) causes among subjects aged ≥ 35 yrs in 10 northern, central and southern Italian cities in 2001-2005 were included in the study. Pollution data for PM(10), nitrogen dioxide and ozone were also obtained. A time-stratified case-crossover analysis was carried out. Different cumulative lags were selected to analyse immediate, delayed, prolonged and best-time effects of air pollution. The shape of the exposure-response curve was analysed. Age, sex, chronic conditions and death site were investigated as potential effect modifiers. We found a 2.29% (95% CI 1.03-3.58%) increase in respiratory mortality at 0-3 days lag. The increase in respiratory mortality was higher in summer (7.57%). The exposure-response curve had a linear shape without any threshold. Sex and chronic diseases modified the relationship between particular matter (PM) and respiratory mortality. The effect of PM on respiratory mortality was stronger and more persistent than that on natural mortality. Females and chronic disease sufferers were more likely to die of a respiratory disease caused by air pollution than males and healthy people.

Personal exposure to particulate matter is associated with worse health perception in adult asthma.

BACKGROUND: Epidemiological studies have shown positive associations between particulate matter (PM) air pollution and short-term mortality and morbidity for asthma. The hypothesis that lung inflammation is responsible for these effects has been tested in panel and controlled exposure studies in asthmatic adults, with inconsistent results. OBJECTIVES: We investigated whether personal exposure to PM10 and PM2.5 were related to changes in the clinical course of asthma and to lung inflammatory responses in adult asthmatics. METHODS: A cohort of 32 asthmatic patients was followed for 2 years. Asthma control test (ACT) and St George's Respiratory Questionnaire (SGRQ) scores, forced expired volume in the first second (FEV1), exhaled nitric oxide (Fe(NO)), and pH of exhaled breath condensate (EBC) were determined on 6 occasions during different seasons. Personal exposure to PM was measured for 24 hours prior to clinical assessments. RESULTS: A 10 microg/m3 increase in PM10 personal exposure was associated with an increase in SGRQ scores (regression coefficient beta = 0.22; 95% confidence interval [CI], -0.005 to 4.451; P =.055) and with a decrease in ACT scores (beta = -0.022; 95% CI, -0.045 to 0.001; P = .060), whereas no associations were found between PM10 and FEV1, Fe(NO), or EBC pH. A positive association was detected between Fe(NO) and outdoor O3 (P = .042) and SO2 (P = .042) concentrations in the subgroup of nonsmoking asthmatics. CONCLUSIONS: We concluded that increments in personal exposure to PM10 are associated with a decrease in asthma control and health-related quality of life. However, this study does not provide evidence that 24-hour exposures to PM are associated with short-term changes in lung function or inflammatory responses of the lung.

Carbon monoxide pollution is associated with decreased lung function in asthmatic adults.

The aim of the present study was to test the effects of exposure to air pollutants on lung function. A panel of 19 adult asthmatics living in Padua (Italy) was followed for five 30-day periods during 2 yrs consecutively (1,492 morning and 1,434 evening measures analysed). Peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV(1)) were measured using a pocket electronic meter. Daily levels of air pollutants and meteorological variables were collected at outdoor city monitoring sites. Significant inverse associations were observed between morning and evening PEF and carbon monoxide level (p = 0.01-0.03), without clear differences between lags (0-3 days). An increment of 1 mg.m(-3) CO was associated with a PEF variation ranging -2.6- -2.8%. All effect estimates on PEF for CO remained significant and even increased after controlling for particles with a 50% cut-off aerodynamic diameter of 10 microm (PM(10)), nitrogen dioxide and sulphur dioxide in single and multi-pollutant models. A similar trend was observed for FEV(1), but the associations were nonsignificant. A nonsignificant inverse relationship between evening PEF and SO(2) was also detected. PEF and FEV(1) were not related to PM(10) and NO(2) concentrations. The present results indicate that, in this panel of adult asthmatics, the worsening of lung function is associated with exposure to gaseous pollutants and occurs at levels of CO and SO(2) lower than current European standards.

Life course social mobility and risk of upper aerodigestive tract cancer in men.

The aim of this study was to explore associations between social mobility and tumours of the upper aero-digestive tract (UADT), focussing on life-course transitions in social prestige (SP) based on occupational history. 1,796 cases diagnosed between 1993 and 2005 in ten European countries were compared with 1585 controls. SP was classified by the Standard International Occupational Prestige Scale (SIOPS) based on job histories. SIOPS was categorised in high (H), medium (M) and low (L). Time weighted average achieved and transitions between SP with nine trajectories: H --> H, H --> M, H --> L, M --> H, M --> M, M --> L, L --> H, L --> M and L --> L were analysed. Odds ratios (ORs) and 95%-confidence intervals [95%-CIs] were estimated with logistic regression models including age, consumption of fruits/vegetables, study centre, smoking and alcohol consumption. The adjusted OR for the lowest versus the highest of three categories (time weighted average of SP) was 1.28 [1.04-1.56]. The distance of SP widened between cases and controls during working life. The downward trajectory H --> L gave an OR of 1.71 [0.75-3.87] as compared to H --> H. Subjects with M --> M and L --> L trajectories ORs were also elevated relative to subjects with H --> H trajectories. The association between SP and UADT is not fully explained by confounding factors. Downward social trajectory during the life course may be an independent risk factor for UADT cancers.

Detection of HPV in mouth floor squamous cell carcinoma and its correlation with clinicopathologic variables, risk factors and survival.

The human papillomavirus (HPV) has been historically associated with head and neck cancers, although its role in oral carcinogenesis remains poorly defined. The purpose of this study was to investigate the prevalence of HPV in mouth floor squamous cell carcinoma and correlate it with clinicopathologic variables, risk factors and survival. HPV presence was evaluated by nested polymerase chain reaction (nPCR) in 29 paraffin-embedded specimens of mouth floor squamous cell carcinoma. HPV DNA was detected in 17.2% (5 of 29) of the specimens; the highest prevalence was observed in non-smoking patients over the age of 60 years. All HPV DNA positive specimens were detected in men with clinical stage III and IV lesions, being most of which were moderately differentiated. Despite this correlation there were no statistically significant differences observed among the analyzed variables, including patients' survival. The relatively low incidence of HPV DNA present in these tumors suggests that this virus does not, by itself, have a significant role in the development of mouth floor squamous cell carcinoma.

Predictors of oropharyngeal cancer survival in Europe.

OBJECTIVES: HPV16-positive oropharyngeal cancer (OPC) patients experience better outcomes compared to HPV16-negative patients. Currently, strategies for treatment de-escalation are based on HPV status, smoking history and disease stage. However, the appropriate cut-point for smoking and the role of other non-clinical factors in OPC survival remains uncertain. MATERIALS AND METHODS: We examined factors associated with OPC outcome in 321 patients recruited in a large European multi-center study. Seropositivity for HPV16 E6 was used as a marker of HPV16 positive cancer. Hazard ratios (HR) and confidence intervals (CI) were estimated using Cox proportional models adjusted for potential confounders. RESULTS: Overall 5-year survival following OPC diagnosis was 50%. HPV16-positive OPC cases were at significantly lower risk of death (aHR = 0.51, 95% CI: 0.32-0.80). A significant effect on OPC survival was apparent for female sex (aHR 0.50: 95% CI: 0.29-0.85) and being underweight at diagnosis (aHR: 2.41, 95% CI: 1.38-4.21). A 10 pack year smoking history was not associated with overall survival. Higher stage at diagnosis appeared as the only factor significantly associated with OPC recurrence (aHR: 4.88, 95% CI: 2.12-11.21). CONCLUSION: This study confirms that HPV16 status is an independent prognostic factor for OPC survival while female sex lowers risk of death and being underweight at diagnosis increases the risk of death. Smoking was not an independent predictor of OPC survival.

Cigar and pipe smoking and lung cancer risk: a multicenter study from Europe.

BACKGROUND: Because limited information is available on the quantitative association between consumption of tobacco products other than cigarettes and lung cancer risk, we undertook a case-control study of this relationship. METHODS: We investigated lung cancer risk among smokers of cigars and/or cigarillos only and of pipes only and compared these risks with the risk of smokers of cigarettes only in a case-control study conducted in seven European areas. Our study population consisted of 5621 male case patients with lung cancer and 7255 male control subjects. Each subject or his proxy was interviewed with respect to the subject's smoking history and other risk factors for lung cancer. RESULTS: The odds ratio (OR) for smoking cigars and cigarillos only was 9.0 (95% confidence interval [CI] = 5.8-14.1), based on 43 exposed case patients and 77 exposed control subjects, and the OR for smoking a pipe only was 7.9 (95% CI = 5.3-11.8), representing 61 case patients and 129 control subjects. The OR for smoking cigarettes only was 14.9 (95% CI = 12.3-18.1), based on 4204 case patients and 3930 control subjects. A dose-response relationship was present for duration of use and cumulative consumption both for cigars and cigarillos and for pipe tobacco. An effect was also suggested for inhalation of cigar and cigarillo smoke. The dose-response relationships between lung cancer risk and either duration of smoking or average and cumulative consumption were similar for cigar and cigarillo smoking, pipe smoking, and cigarette smoking. CONCLUSION: Our results suggest that smoking of European cigars, cigarillos, and pipe tobacco might exert a carcinogenic effect on the lung comparable to that of cigarettes.

Multicenter case-control study of exposure to environmental tobacco smoke and lung cancer in Europe.

BACKGROUND: An association between exposure to environmental tobacco smoke (ETS) and lung cancer risk has been suggested. To evaluate this possible association better, researchers need more precise estimates of risk, the relative contribution of different sources of ETS, and the effect of ETS exposure on different histologic types of lung cancer. To address these issues, we have conducted a case-control study of lung cancer and exposure to ETS in 12 centers from seven European countries. METHODS: A total of 650 patients with lung cancer and 1542 control subjects up to 74 years of age were interviewed about exposure to ETS. Neither case subjects nor control subjects had smoked more than 400 cigarettes in their lifetime. RESULTS: ETS exposure during childhood was not associated with an increased risk of lung cancer (odds ratio [OR] for ever exposure = 0.78; 95% confidence interval [CI] = 0.64-0.96). The OR for ever exposure to spousal ETS was 1.16 (95% CI = 0.93-1.44). No clear dose-response relationship could be demonstrated for cumulative spousal ETS exposure. The OR for ever exposure to workplace ETS was 1.17 (95% CI = 0.94-1.45), with possible evidence of increasing risk for increasing duration of exposure. No increase in risk was detected in subjects whose exposure to spousal or workplace ETS ended more than 15 years earlier. Ever exposure to ETS from other sources was not associated with lung cancer risk. Risks from combined exposure to spousal and workplace ETS were higher for squamous cell carcinoma and small-cell carcinoma than for adenocarcinoma, but the differences were not statistically significant. CONCLUSIONS: Our results indicate no association between childhood exposure to ETS and lung cancer risk. We did find weak evidence of a dose-response relationship between risk of lung cancer and exposure to spousal and workplace ETS. There was no detectable risk after cessation of exposure.

Clinical evaluation of an ointment with 10% metronidazole and 2% lidocaine in the treatment of alveolitis.

AIM: In this study, the authors evaluate the use of a 10% metronidazole and 2% lidocaine ointment, using a lanolin base and mint as flavoring, to treat alveolitis in humans. METHODS: Twenty-five patients, with a diagnosis of alveolitis, were treated in the following way: locoregional anesthesia; surgical cleaning of the socket with alveolar curettes; saline solution irrigation with a 20 ml disposable syringe; and complete filling of the socket with the ointment. RESULTS: The analysis of the results showed that the painful symptoms were severe before and on the day of the treatment in 17 (68%) of the 25 patients treated. Post-treatment analysis presented 2 patients (18%) with severe painful symptoms after 24 h of the treatment and complete remission of painful symptoms after 48 h of the treatment with the ointment. CONCLUSIONS: Based on the results, it is possible to conclude that the 10% metronidazole and 2% lidocaine ointment, with mint flavoring and lanolin as a base, can be used to treat alveolitis.

Target organs for carcinogenicity of chemicals and industrial exposures in humans: a review of results in the IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans.

Epidemiological observations indicate that cancers affecting different organs and systems in humans have different causes. At the descriptive level, cancer incidence and mortality rates exhibit patterns of geographic and temporal variation which are distinct and separate for each cancer site and even, at a given site, for different histological types (for instance, increasing squamous cell carcinoma of the lung and decreasing stomach cancer in most developed countries in recent decades). The existence of these distinct patterns in itself indicates that different causes are at the origin of cancers at different sites. Hence, it is of scientific and practical importance not only to identify agents that are carcinogenic to humans but also to specify as definitely as possible the target organ(s) of their action. This is done in the present review of results in the International Agency for Research on Cancer Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans.

Effect of different approaches to treatment of smoking as a potential confounder in a case-control study on occupational exposures.

AIM: To evaluate the effect of different approaches to treatment of smoking as a potential confounder in an occupational study of lung cancer. METHODS: Data were used from a case-control study on 956 men with lung cancer and 1253 population controls recruited in two northern Italian areas during 1990-1992. The risk of lung cancer associated with 11 selected job titles and eight selected industrial activities was estimated using seven different methods to treat smoking history. To evaluate the confounding effect of smoking, odds ratios obtained using the first six models were compared with estimates from the seventh and most complex model, in which cumulative tobacco consumption and time since cessation were considered. RESULTS: Although crude odds ratios for some of the occupational categories were biased by up to 25%, such bias decreased to less than 10% when a simple model including smoking status (never, ex-, current) was used. CONCLUSIONS: In occupational studies on lung cancer risk, information on smoking status may allow satisfactory control of the potential confounding effect of the habit.

Lung cancer risk in nonsmokers and GSTM1 and GSTT1 genetic polymorphism.

Glutathione S-transferase (GST) polymorphism may contribute to the individual variability in detoxifying lung carcinogens. This effect might be particularly relevant at low-level exposure to environmental carcinogens, such as in nonsmokers exposed to environmental tobacco smoke (ETS). We conducted a case-control study among 122 nonsmoking lung cancer cases and 121 nonsmoking controls from eight countries. Information on environmental exposures was obtained through a personal interview. The presence of GSTM1 and GSTT1 genes was determined using multiplex PCR. GSTM1-positive samples were then analyzed for *1A and *1B polymorphism using an allele-specific amplification-PCR method. GSTM1*2 (null) individuals had an odds ratio (OR) of lung cancer of 1.5 [95% confidence interval (CI), 0.9-2.7]; the risk associated with this genotype was higher for cases with squamous and small cell carcinomas (OR, 2.3; 95% CI, 0.9-6.1) than for cases with adenocarcinomas. It was also elevated in individuals with long-term exposure to indoor wood combustion (OR, 3.1; 95% CI, 0.9-9.9), in subjects who mainly lived in a rural setting (OR, 3.6; 95% CI, 1.0-13), and in cases exposed to occupational carcinogens (OR, 10.7; 96% CI, 0.4-260) but not in subjects exposed to ETS. GSTT1*2 subjects did not show a risk of lung cancer. Our study suggests that the effect of GSTM1 polymorphism in nonsmokers is similar to that found in smokers. It does not seem to interact with ETS exposure, although we cannot exclude that it does in association with exposure to other specific environmental carcinogens.

Updating lung cancer mortality among a cohort of man-made mineral fibre production workers in seven European countries.

A historical cohort of 21,967 workers ever employed in 13 European factories manufacturing various types of man-made mineral fibres (MMMF) was observed until 1982. Overall there were 2719 deaths (standardised mortality ratio (SMR) = 111) of which 189 were from lung cancer (SMR = 125). For the glasswool and rockwool/slagwool production subcohorts the lung cancer SMRs rose with time since first exposure, exceeding 170 for the period of 30 or more years. Adjustment for regional variations in mortality substantially reduced the excess in the glasswool group, but not in the rockwool/slagwool. In neither subgroup was there any relationship of lung cancer mortality with length of employment. During the early years of rockwool/slagwool production there was the potential for much higher fibrous dust exposure than at present, because of the absence of dust suppressing oil and/or the use of a batch production process. In addition slag was widely used as a raw material. Amongst workers employed during the early phase, there were 10 lung cancer deaths giving SMRs of 270 and 244 for the periods 20-29 and 30 or more years since first exposure. This group accounts for most of the absolute excess of lung cancer for the rockwool/slagwool plants.

Development and use of a welding process exposure matrix in a historical prospective study of lung cancer risk in European welders.

A welding process exposure matrix has been developed relating 13 welding process-welded metal combinations to average exposure levels for total welding fumes, total chromium, chromium (VI) and nickel. Quantitative estimates were derived from consultation of literature sources and of some company data. This matrix was applied to the welding histories of 11,092 welders in the framework of an IARC multicentre study. When detailed welding history was not available at the individual level the average company welding practice profile was applied. No dose-response relationship emerged for lung cancer risk with cumulative dose of the carcinogens chromium (VI) and nickel for stainless steel welders. Dilution of the dose-response relationship could result from between-plant and within-plant variability, and exposure in jobs not accounted for in the study, but not from the partial use of company versus individual data. It is also possible that there is no increased risk related to chromium and nickel exposure in this group of workers. Matrix exposure estimates would need to be validated and the matrix possibly refined by comparison with a variety of comprehensive welding exposure data sets.