Oral Cancer Research Articles

The Trend in Age-Adjusted Incidence of Head and Neck Cancer in South Korea over the Past 20 Years.

We aimed to calculate the age-adjusted incidence rate of head and neck cancer (HNC) in South Korea from 1999 to 2020 and investigate the incidence trend of HNC excluding the effect of population aging. Data were obtained from the Cancer Registration Statistics Program. All 12 types of HNCs were analyzed. For each HNC type, the crude incidence rate and number of new cases during 1999-2020 are presented according to sex and age group. Age-adjusted incidence rates were calculated based on the World Standard Population (WHO 2000-2025), and its trends were also measured. Although the crude incidence rates of all HNCs have been steadily increasing from 1999 to 2020, the absolute values were very low in most cases, less than 2/100,000. The male-to-female ratio was 1 or higher for all HNCs except thyroid cancer, and 10 or higher for laryngeal cancer and hypopharyngeal cancer. The trend of age-adjusted incidence was a gradual increase for tongue cancer, tonsil cancer, major salivary gland cancer, and thyroid cancer, a decrease for laryngeal cancer, and no significant change for the remaining HNCs. Excluding the population aging effect, tongue cancer, tonsil cancer, major salivary gland cancer, and thyroid cancer among HNCs have been increasing in South Korea over the past 20 years, while laryngeal cancer has been decreasing.

Artificial Intelligence in Oral Cancer: A Comprehensive Scoping Review of Diagnostic and Prognostic Applications

Artificial Intelligence in Oral Cancer: A Comprehensive Scoping Review of Diagnostic and Prognostic Applications

Potassium titanyl phosphate laser resection of tongue T1/T2 squamous cell carcinoma - a cross-sectional study of quality of life and nutritional outcomes.

Increasing emphasis has been placed on measurement of quality of life (QOL) as a central criterion for assessment of success of any medical treatment. The aim of our study was to assess the nutritional and quality of life of patient-reported outcomes among patients who have undergone laser resection of tongue cancer. A cross-sectional study was undertaken of patients treated with KTP laser resection of T1/T2 tongue squamous cell carcinoma (SCC) between 2011-2019. University of Washington Quality of life 4 questionnaire (UW-QOL) and the abridged scored patient-generated subjective global assessment (AB PG-SGA) were used. Scores were correlated to analyse the QOL and nutritional status. 20 patients participated and were categorised into three groups based on AB PG-SGA score. The physical and social-emotional QOL scores were higher for patients who had a better nutritional status. There was a linear negative correlation between the AB PG-SGA score, physical and social-emotional domains of the QOL. No association was found between histopathological differentiation, neck dissection surgeries and the AB PG-SGA score. The use of the KTP laser to excise tongue T1 and T2 SCC yields acceptable results in terms of QOL and patient-reported nutritional outcomes. There is a significant trend identifying that as a patient's nutritional status improves quality of life is enhanced and vice versa. The QOL and the nutritional status of patients were not affected by the different histopathological grades of SCC or whether they had undergone a neck dissection or not.

Boswellic acid exerts anti-tumor effect in oral squamous cell carcinoma by inhibiting PI3K/AKT1 mediated signaling pathway.

Boswellic acid (BA) is a bioactive compound derived from Boswellia trees. This study aims to investigate the anti-cancer properties of BA against KB oral squamous cancer cells and elucidate the underlying mechanisms. Escalating doses of BA were administered to KB cells, and various analyses were conducted using bioinformatic tools such as GEO, GEO2R, and STITCH database. MTT and trypan blue assays has been validated to measure the cytotoxicity by treating BA in KB Cells. Flow cytometry assessed cell cycle progression, apoptosis induction, and metabolic alterations. Network analysis identified relevant signaling pathways, while RT-PCR validated mRNA expression changes. Docking studies by Autodock evaluated beta-BA's binding affinity with mTOR-mediated pathways. BA effectively hindered KB cell progression, inducing G0/G1 phase cell cycle arrest and apoptosis. It also inhibited aerobic glycolysis, a hallmark of oral cancer cells. Network analysis revealed involvement in apoptosis and mTOR targets. RT-PCR confirmed downregulation of genes associated with aerobic glycolysis and apoptosis. Docking studies indicated strong binding between BA and mTOR pathways. BA shows promise in inhibiting KB oral squamous cancer cell growth. These findings underscore its potential as a treatment for oral cancer. Further research and clinical studies are needed to unlock its full therapeutic potential.

Postoperative Radiotherapy ± Cetuximab for Intermediate-Risk Head and Neck Cancer.

Radiotherapy (RT)/cetuximab (C) demonstrated superiority over RT alone for locally advanced squamous head and neck cancer. We tested this in completely resected, intermediate-risk cancer. Patients had squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx, or larynx, with one or more risk factors warranting postoperative RT. Patients were randomly assigned 1:1 to intensity-modulated RT (60-66 Gy) with once-per-week C or RT alone. The primary hypothesis was that RT + C would improve overall survival (OS) in randomly assigned/eligible patients, with a prespecified secondary plan to test this in the human papillomavirus (HPV)-negative subpopulation. Disease-free survival (DFS) and toxicity were secondary end points. OS and DFS were tested via stratified log-rank test; toxicity was compared via Fisher's exact test. We enrolled 702 patients from November 2009 to March 2018; 577 were randomly assigned/eligible. Most (63.6%) had oral cavity cancer and most (84.6%) had high epidermal growth factor receptor expression. There were fewer deaths (184) than expected. OS (median follow up, 7.2 years) was not significantly improved (hazard ratio [HR], 0.81; one-sided P = .0747; 5-year OS 76.5% v 68.7%), but DFS was (HR, 0.75; one-sided P = .0168; 5-year DFS 71.7% v 63.6%). Benefit of RT + C was only seen in the HPV-negative subpopulation (80.2% of patients in the trial). Grade 3-4 acute toxicity rates were 70.3% (RT + C) versus 39.7% (RT; two-sided P < .0001), mostly skin and/or mucosal effects. Late grade ≥3 toxicity rate was 33.2% (RT + C) versus 29.0% (RT; two-sided P = .3101). There were no grade 5 toxicities in either arm. RT + C significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT + C is an appropriate option for carefully selected patients with HPV-negative disease.

Compartmental Tongue Surgery Revisited: Oncologic Outcomes in Over 100 cT4a Oral Tongue Cancer Patients from a Single Cancer Institute

Compartmental Tongue Surgery Revisited: Oncologic Outcomes in Over 100 cT4a Oral Tongue Cancer Patients from a Single Cancer Institute

Copper-nitrite complexes release nitric oxide and selectively induce oral precancer and cancer cell apoptosis.

Nitric oxide (NO) is a small, short-lived gas molecule that influences various critical functions in living organisms. It involves multiple physiological processes, including cardiovascular function, metabolism, neurotransmission, immunity, and aberrant NO signaling leads to various disorders such as cardiovascular diseases, diabetes, and cancers. In this study, we explored the potential application of copper-nitrite complexes in treating oral precancer and cancer. The copper-nitrite complexes, L1Cu(NO2) and L2Cu(NO2), were shown to release NO into cells and selectively induce cytotoxicity to oral precancer and cancer cells. Notably, L1Cu(NO2) inhibited oral cancer cell proliferation by causing G0/G1 phase cell cycle arrest. Furthermore, L1Cu(NO2) induced cell apoptosis and upregulated the expression of p-PRAS40 (proline-rich Akt substrate of 40kDa) in oral cancer cells. All these results reveal the therapeutic potential of copper-nitrite complexes, especially L1Cu(NO2), to be developed as a targeted therapy against oral precancer and cancer.

Stevioside as a potential therapeutic agent: inhibiting cell growth and regulating epithelial-mesenchymal transitions in oral squamous cell carcinoma.

Oral cancer is a predominant and aggressive form of head and neck cancer with limited treatment options. Stevioside, a naturally occurring biocompatible compound, has gained attention for its potential therapeutic properties, although its molecular mechanistic role in OSCC merely understood. This study aims to elucidate the impact of stevioside on OSCC cells, focusing on its inhibitory effects on cell proliferation and epithelial-mesenchymal transitions (EMT). KB cells, representative of OSCC, were subjected to stevioside treatment in a time-dependent manner. The findings obtained from the MTT assay revealed a notable suppression of KB cell growth following 48 hours of treatment with stevioside. The IC<inf>50</inf> values, which represent the concentration at which the inhibitory effect of stevioside is at 50% at 110.54 µM, as determined by this assay, were subsequently utilized further for the analysis of gene expression through RT-PCR. Furthermore, our investigation involved the examination of EMT-related genes (ECADH, SNAIL1, SLUG, and VIM) using molecular docking analysis. In conclusion, this study sheds light on the significant role of stevioside in oral cancer. The observed inhibition of KB cell proliferation and its pronounced impact on EMT-related gene expression indicate the potential of stevioside as a promising therapeutic agent in the context of OSCC. The multifaceted effects of stevioside on OSCC cells present an exciting avenue for advancing our understanding of this devastating disease and the development of innovative therapeutic strategies.

Associations between cancer-related coping and depressive symptoms in oral cancer patients

ObjectivesSpecific coping styles have been found to influence several aspects of psychological health in various ways among cancer patients. Therefore, the aim of the current study was to examine whether different coping styles are associated with depressive symptoms in oral cancer patients.MethodsThe current cross-sectional study was conducted from May 2021 to October 2022 in Liaoning Province, China. A total of 229 patients were included. In addition to demographic and clinical information, the participants completed questionnaires on different coping styles and depressive symptoms. Multivariate linear regression was conducted to identify the influencing factors of depressive symptoms.ResultsThe prevalence of depressive symptoms was 65.5% in oral cancer patients. Negative emotion and positive attitude coping explained an additional 50.1% of the variance in depressive symptoms. Negative emotion coping was significantly and positively associated with depressive symptoms (β = 0.596, p < 0.001), whereas positive attitude coping was significantly and negatively related to depressive symptoms (β=-0.275, p < 0.001). In addition, distant metastasis was associated with depressive symptoms (β = 0.084, p < 0.047).ConclusionsIn our sample, more than half of the oral cancer patients experienced depressive symptoms. Interventions based on decreasing negative coping and increasing positive coping should be implemented to help patients cope with mental health problems and achieve psychological adaptation after oral cancer diagnosis and treatment.

Unmasking the potential: a historical perspective on the evolution of exfoliative cytology in oral cavity neoplasms.

Exfoliative cytology has proven to be a valuable diagnostic tool in the early detection of malignant neoplasms. However, its application in the oral cavity has been met with skepticism and limited investigation due to the perception that clinical examination alone is sufficient for early diagnosis. Nonetheless, recent research efforts have focused on the utility of exfoliative cytology in oral cavity neoplasms, motivated by the high mortality rate associated with oral cancer. This manuscript reviews the historical development of exfoliative cytology in the oral cavity, highlighting key findings and advancements in the field. Early studies demonstrated the presence of neoplastic cells in oral cavity lesions and emphasized the diagnostic potential of cytology. Subsequent research explored different staining methods and observed the differential reaction of oral cavity cells to radiation therapy. The diagnostic accuracy of exfoliative cytology was reported to be as high as 92%, with a significant number of cases diagnosed as carcinomas without any clinical suspicion. The technique also proved valuable in identifying precancerous and dysplastic lesions and obviating the need for unnecessary biopsies. The manuscript delves into the difficulties encountered in sampling techniques and stresses the significance of appropriate specimen collection and handling. Various staining methods, including Papanicolaou and acridine orange, were utilized for cytological analysis. The manuscript emphasizes the extensive use of exfoliative cytology in oral cavity examinations and stresses the importance of recognizing it as a crucial diagnostic tool. Various studies have reported high positivity rates and the detection of clinically unsuspected malignant lesions. The authors recommend extensive use of exfoliative cytology in routine practice and underscore the necessity of proper sampling and evaluation techniques.

Convolutional neural networks for accurate real-time diagnosis of oral epithelial dysplasia and oral squamous cell carcinoma using high-resolution in vivo confocal microscopy

Oral cancer detection is based on biopsy histopathology, however with digital microscopy imaging technology there is real potential for rapid multi-site imaging and simultaneous diagnostic analysis. Fifty-nine patients with oral mucosal abnormalities were imaged in vivo with a confocal laser endomicroscope using the contrast agents acriflavine and fluorescein for the detection of oral epithelial dysplasia and oral cancer. To analyse the 9168 images frames obtained, three tandem applied pre-trained Inception-V3 convolutional neural network (CNN) models were developed using transfer learning in the PyTorch framework. The first CNN was used to filter for image quality, followed by image specific diagnostic triage models for fluorescein and acriflavine, respectively. Images were categorised based on a histopathological diagnosis into 4 categories: no dysplasia, lichenoid lesions, low-grade dysplasia and high-grade dysplasia/oral squamous cell carcinoma (OSCC). The quality filtering model had an accuracy of 89.5%. The acriflavine diagnostic model performed well for identifying lichenoid (AUC = 0.94) and low-grade dysplasia (AUC = 0.91) but poorly for identifying no dysplasia (AUC = 0.44) or high-grade dysplasia/OSCC (AUC = 0.28). In contrast, the fluorescein diagnostic model had high classification performance for all diagnostic classes (AUC range = 0.90–0.96). These models had a rapid classification speed of less than 1/10th of a second per image. Our study suggests that tandem CNNs can provide highly accurate and rapid real-time diagnostic triage for in vivo assessment of high-risk oral mucosal disease.

Long-term exposure to fine particulate matter constituents and the prognosis of oral cancer patients: A prospective study in Southeastern China.

Evidence on the association of long-term exposure to fine particular matter (PM2.5) and its chemical constituents with the prognosis of oral cancer patients is limited. We identified 1673 oral cancer patients from 2011 to 2021 in Fujian, China. We evaluated annual average concentrations of PM2.5 and constituents, including nitrate, sulfate, ammonium, black carbon (BC), and organic matter (OM), using bilinear interpolation based on the patients' residential address. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95 % confidence interval. We used counterfactual analyses to evaluate the population attributable fractions (PAF). During a median follow-up duration of 3.58 years, 484 (28.93 %) died. For per-SD increase in PM2.5, nitrate, sulfate, ammonium, OM, and BC, the adjusted HRs were 1.18, 1.16, 1.18, 1.19, 1.17, and 1.20 for all-cause mortality, and 1.26, 1.22, 1.27, 1.28, 1.24, and 1.29 for oral cancer-specific mortality, respectively. The corresponding PAFs of PM2.5, nitrate, sulfate, ammonium, OM, and BC were 25.43 %, 24.19 %, 25.73 %, 25.78 %, 25.28 %, and 26.59 % for all-cause mortality, and 26.61 %, 24.19 %, 27.15 %, 27.01 %, 26.19 %, and 28.41 % for oral cancer-specific mortality, respectively. Our study showed that long-term exposure to PM2.5 and constituents might be an important risk factor for mortality among oral cancer patients.

Desmoglein-2 was a novel cancer-associated fibroblasts-related biomarker for oral squamous cell carcinoma

BackgroundOral squamous cell carcinoma (OSCC) is the most common type of oral cancer with alarmingly high morbidity. The cancer-associated fibroblasts (CAFs) play a pivotal role in tumor development, while their specific mechanisms in OSCC remains largely unclear. Our object is to explore a CAFs-related biomarker in OSCC.MethodsSingle-cell RNA sequencing (ScRNA-seq) analysis was used to pinpoint CAF clusters in OSCC samples. Differentially expressed genes and Cox regression analyses were used to identify candidate genes, and their functions were evaluated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The prognostic performance of the identified biomarker was evaluated using receiver operating characteristic analysis. The qPCR and western blot were used to assess gene expression. The hub gene related immune characteristics were analyzed in independent cohorts, and gene expression differences between different immunotherapy response groups were investigated using Pearson correlation analysis.ResultsDesmoglein-2 (DSG2) was identified as a CAFs-related biomarker in OSCC exhibiting elevated expression compared to controls and being associated with poor prognosis. Enrichment analyses revealed that DSG2 was involved in signal transduction pathways like focal adhesion. The Area Under Curve values of DSG2 in predicting prognosis exceeded 0.6 in both training-set and validation-set. Furthermore, patients with low DSG2 expression were more likely to benefit from immunotherapy than those DSG2 highly expressed patients.ConclusionOur study identified DSG2 as a reliable CAFs-related prognostic biomarker in OSCC, providing a new reference for the mechanistic understanding and target therapy of this malignancy.

Predictive Value of the Loss of pRb Expression in the Malignant Transformation Risk of Oral Potentially Malignant Disorders: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to qualitatively and quantitatively evaluate the current evidence on the significance of the loss of early stages of oral carcinogenesis in lesions diagnosed according to clinical and/or histopathological criteria and their evolution to oral cancer. We searched MEDLINE (through PubMed), Embase, Scopus and Web of Science for primary-level studies published before November 2024, designed as prospective or retrospective longitudinal cohorts, and not restricted by language or publication date. The risk of bias was critically assessed using the QUIPS tool. Meta-analyses, heterogeneity exploration, sensitivity and small-study effect analyses were conducted. The inclusion criteria were met by six primary-level studies, which recruited 330 patients with OPMDs with follow-up data. The loss of pRb expression, assessed through immunohistochemistry, was significantly associated with a higher malignant transformation risk of OPMDs (RR = 1.92, 95%CI = 1.25-2.94, p = 0.003). The leukoplakia subgroup retained this significant association (p = 0.006), being the OPMD where the loss of pRb expression showed the best predictive value for malignant transformation (RR = 2.00, 95%CI = 1.22-3.29). Regarding the immunohistochemical technique and scoring methods, better performance and results were achieved by applying a cutoff point > 10% pRb-positive cells with nuclear staining (RR = 2.10, 95%CI = 1.30-3.38, 95%CI = 0.002). The present systematic review and meta-analysis supports that the loss of expression of the tumor suppressor pRb, assessed through immunohistochemistry, is a predictor of the malignant transformation risk of oral leukoplakias. Future studies are needed in other OPMDs following the recommendations provided based on current evidence gaps.

TNF-α polymorphism in oral cancer and oral potentially malignant disorders: meta-analysis and investigation as a potential tool to determine individual susceptibility and the prognosis.

There is increasing evidence that tumour necrosis factor alpha (TNF-α) gene polymorphisms may promote development and spread of cancer through transitions at different loci that lead to its altered expression. However, data on TNF-α gene polymorphisms in oral cancer remain highly controversial. This meta-analysis was performed to determine the impact of TNF-α gene polymorphisms on oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD). An electronic search was conducted in the PubMed, Cochrane Library, Google Scholar, and Web of Science databasesto identify original articles reporting TNF-α polymorphism in OSCC and OPMD. The articles were examined by two independent authors. Data from the included articles were compiled and tabulated. Risk of bias was analysed. Overall, 11 eligible articles that included 1070 cases of OSCC and 641 cases of OPMD in which TNF-α polymorphism was studied, were included for quantitative analysis. It was found that both TNF-α -308 and -238 polymorphisms were significantly associated with the development of oral cancer. TNF-α polymorphism was significantly associated with OSCC and OPMD. Moreover, in polymorphisms of TNF-α at both -308 and -238, the G allele, especially the homozygous form (GG), was found to be associated with oral cancer.

ChatGPT and oral cancer: a study on informational reliability

BackgroundArtificial intelligence (AI) and large language models (LLMs) like ChatGPT have transformed information retrieval, including in healthcare. ChatGPT, trained on diverse datasets, can provide medical advice but faces ethical and accuracy concerns. This study evaluates the accuracy of ChatGPT-3.5's answers to frequently asked questions about oral cancer, a condition where early diagnosis is crucial for improving patient outcomes.MethodsA total of 20 questions were asked to ChatGPT-3.5, selected from Google Trends and questions asked by patients in the clinic. The responses provided by ChatGPT were evaluated for accuracy by medical oncologists and oral and maxillofacial radiologists. Inter-rater agreement was assessed using Fleiss’s and Cohen kappa tests. The scores given by the specialties were compared with the Mann-Whitney U test. The references provided by ChatGPT-3.5 were evaluated for authenticity.ResultsOf the 80 responses from 20 questions, 41 (51.25%) were rated as very good, 37 (46.25%) as good, 2 (2.50%) as acceptable. There was no significant difference between oral and maxillofacial radiologists and medical oncologists in all 20 questions. Of the 81 references to ChatGPT-3.5 answers, only 13 were scientific articles, 10 were fake, and the remaining references were data from websites.ConclusionChatGPT provided reliable information about oral cancer and did not provide incorrect information and suggestions. However, all information provided by ChatGPT is not based on real references.

Exploring dental students' knowledge on oral cancer prevention: a cross-sectional study in Moldova, Armenia, and Belarus

BackgroundSurvival rate of patients with oral cancer (OC) remains to be very low despite advancements in therapy and surgical techniques. This is attributed to the fact that most OC cases are discovered at a late stage. Dentists play a vital role in early detection of OC through oral mucosal examination, and in informing the patients about avoidable risk factors of the disease, such as tobacco and excessive alcohol use. This study aimed at evaluating knowledge about OC among dental students in Moldova, Armenia and Belarus; three former soviet countries with high rates of tobacco use.MethodsThis was a cross-sectional, multi-country study based on self-administered questionnaire. Dental students in their clinical years at three dental faculties in Moldova, Armenia and Belarus were invited to participate in the study. Data collection took place during the period May to September 2019. Association between different categorical variables was investigated using Chi-squared test. A knowledge score ranging from 0–14 was constructed from the obtained data. Differences in the knowledge score between different groups of students was investigated using either student`s t-test whenever comparing two groups, or One-way ANOVA with Bonferroni`s correction for three or more groups. The level of significance was set to 0.05 for all statistical tests.ResultsA total of 642 dental students participated in the study. The mean knowledge score was found to be 6.62 ± 2.61, with 45% of the students scoring below the mean. Students from Belarus had the highest score (7.3 ± 2.14) in comparison to Armenia (6.66 ± 2.64) and Moldova (5.66 ± 2.81), as revealed by ANOVA test. However, we observed a significant increase (p-value < 0.001, ANOVA) in the students` knowledge score as they proceed through study years from third (6.07 ± 2.61) to fifth year (7.49 ± 2.48). In addition, we found that Students with current or previous cigarette smoking habits had significantly (p-value < 0.001, student`s t-test) lower mean knowledge score (5.96 ± 2.82) when compared to students who have never been smokers (6.98 ± 2.42).ConclusionsThe present study reveals notable gaps in OC knowledge and concerning tobacco use behaviors among dental students in Moldova, Belarus, and Armenia. By providing comprehensive education on risk factors and addressing personal habits, dental schools can better prepare future professionals to play a critical role in OC prevention and management.

Development and Evaluation of an Automated Multimodal Mobile Detection of Oral Cancer (mDOC) Imaging System to Aid in Risk-based Management of Oral Mucosal Lesions.

Oral cancer is a major global health problem. It is commonly diagnosed at an advanced stage although often preceded by clinically visible oral mucosal lesions, termed oral potentially malignant disorders associated with an increased risk for oral cancer development. There is an unmet clinical need for effective screening tools to assist front-line healthcare providers to determine which patients should be referred to an oral cancer specialist for evaluation. This study reports the development and evaluation of the mobile Detection of Oral Cancer (mDOC) imaging system and an automated algorithm that generates a referral recommendation from mDOC images. mDOC is a smartphone-based autofluorescence and white light imaging tool that captures images of the oral cavity. Data were collected with mDOC from a total of 332 oral sites in a study of 29 healthy volunteers and 120 patients seeking care for an oral mucosal lesion. A multimodal image classification algorithm was developed to generate a recommendation of "Refer" or "Do Not Refer" from mDOC images, using expert clinical referral decision as the ground truth label. A referral algorithm was developed using cross-validation methods on 80% of the dataset, then retrained and evaluated on a separate holdout test set. Referral decisions generated in the holdout test set had a sensitivity of 93.9% and a specificity of 79.3% with respect to expert clinical referral decisions. The mDOC system has the potential to be utilized in community physicians' and dentists' offices to help identify patients who need further evaluation by an oral cancer specialist.

Strong inorganic acid mists and respiratory tract cancers: a meta-analysis.

Exposure to strong inorganic acid mists (SIAMs) in the workplace has been linked to respiratory tract cancers. We conducted a meta-analysis of cohort and case-control studies examining the association between occupational SIAMs and respiratory tract cancers other than laryngeal cancer, which is already established. Studies mentioned in the 1992 IARC Monograph on carcinogenicity of SIAMs were combined with later studies identified from a systematic search of Scopus, PubMed and Embase. Forest plots of relative risks (RR) and odds ratios were constructed for the 34 identified studies. A random-effects model was used to address heterogeneity. An association between the roles associated with occupational SIAMs exposure and risk of lung (RR = 1.17; 95% confidence interval [CI] = 1.05-1.32), and nasal cancers (RR = 3.30, 95% CI = 1.16-9.41) was found. The risk of oral and pharyngeal cancer was also associated with SIAMs exposure-related roles (RR = 1.59, 95% CI = 0.98-2.57). Results did not differ by study design, gender or outcome for all three cancers. A positive association for lung cancer was found with chemical (RR = 1.25, 95% CI = 1.13-1.38), and metal and steel industries (RR = 1.19, 95% CI = 1.04-1.37), as well as for oral and pharyngeal cancer with chemical industry (RR = 1.72, 95% CI = 1.57-1.89). We checked publication bias for lung (p = 0.35), oral and pharyngeal (p = 0.02) and nasal cancer (p = 0.40). Our study showed an association between occupational SIAM exposure and risk of lung, nasal, and possibly oral and pharyngeal cancers. However, weaknesses in the recording of confounding and exposure data in the currently available literature were found.

Non-smoking, non-drinking, oral squamous cell carcinoma patients are a distinct and clinically significant group.

Carcinogenesis of oral squamous cell carcinoma (OSCC) has long been associated with exposure to tobacco smoke and alcohol consumption. Some centres have reported that non-smoking non-drinking (NSND) patients represent a significant and increasing proportion of OSCC cases with reports of poorer outcomes. Demographic characteristics are variably reported for this group and carcinogenesis is not fully understood. We present the largest cohort study to date in this subject area and sought to better understand demographics and survival. We interrogated 541 OSCC patients by retrospective analysis to assess risk factor status, disease characteristics and survival. Patients were categorised according to smoking and alcohol exposure with non-smoker (NS) status defined as less than five cigarettes per week with no history of use greater than this. Non-drinker (ND) status was defined as less than three standard drinks per week with no history of alcohol consumption greater than this. Those both NS and ND were categorised as NSND. Subsite, tumour stage and treatment were recorded along with evidence of cervical nodal and distant metastasis. These patients were more likely to be female, older and present with early-stage disease. Tumour site was tongue, maxillary alveolus and buccal mucosa, at variance with the smoker drinker groups. NSNDs comprise a significant proportion our OSCC population. These patients were more likely to be female, older and present with early-stage disease. Tumour site was tongue, maxillary alveolus and buccal mucosa, at variance with the smoker drinker groups. Thus, NSNDs are a clinically distinct and significant group in oral cavity cancer management.