MEDLINE contains well over 14,000 papers revealed by a search using keywords 'oral squamous cell cancer' or 'oral squamous cell carcinoma', over 27,000 using 'oral carcinoma' and over 48,000 using the keywords 'oral cancer'. It is difficult to see how clinicians could keep abreast of such a subject. This paper attempts to help by providing an overview of the aetiopathogenesis of oral squamous cell carcinoma (OSCC), discussing changes in epidemiology and increasing awareness of the wide range of risk factors, emphasising the genetic background to cancer susceptibility and the genetic changes associated with progression to OSCC and highlighting clinical implications.

Oral squamous cell carcinoma: overview of current understanding of aetiopathogenesis and clinical implications.

Epidemiological data from oral squamous cell carcinoma (OSCC) is mostly derived from North American, European and East Asian populations. OBJECTIVE: The aim of this study was to report the demographic and clinicopathological features from OSCC diagnosed in an Oral Pathology service in southeastern Brazil in an 8-year period. MATERIAL AND METHODS: All OSCC diagnosed from 2005 to 2012 were reviewed, including histological analysis of all hematoxylin and eosin stained slides and review of all demographic and clinical information from the laboratory records. RESULTS: A total of 346 OSCC was retrieved and males represented 67% of the sample. Mean age of the patients was 62.3 years-old and females were affected a decade older than males (p<0.001). Mean time of complaint with the tumors was 10 months and site distribution showed that the border of the tongue (37%), alveolar mucosa/gingiva (20%) and floor of mouth/ventral tongue (19%) were the most common affected sites. Mean size of the tumors was 3.4 cm, with no differences for males and females (p=0.091) and males reported both tobacco and alcohol consumption more frequently than females. Histological grade of the tumors revealed that 27%, 40% and 21% of the tumors were, respectively, classified as well-, moderately- and poorly-differentiated OSCC, 26 cases (7.5%) were microinvasive OSCC and 17 cases were OSCC variants. OSCC in males mostly affected the border of tongue, floor of mouth/ventral tongue and alveolar mucosa/gingival, while they were more frequent on the border of tongue, alveolar mucosa/gingival and buccal mucosa/buccal sulcus in females (p=0.004). CONCLUSIONS: The present data reflect the epidemiological characteristics of OSCC diagnosed in a public Oral Pathology laboratory in southeastern Brazil and have highlighted several differences in clinicopathological features when comparing male and female OSCC-affected patients.

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Oral squamous cell carcinoma: clinicopathological features from 346 cases from a single oral pathology service during an 8-year period.

The authors investigated the joint effects of tobacco and alcohol consumption on the risk of squamous cell carcinomas of the upper aero-digestive tract (UADT) using data from a hospital-based case-control study conducted in southern Brazil, 1986-1989. A total of 784 cases of cancers of the mouth, pharynx, and larynx and 1,578 non-cancer controls matched on age, sex, hospital catchment area, and period of admission were interviewed about their smoking and drinking habits and other characteristics. Using logistic regression, evidence was found for interaction between the cumulative exposures for smoking and alcohol on UADT cancer risk. The joint effects for pharyngeal cancers exceeded the levels expected under a multiplicative model for moderate smokers (p = 0.007). There was little statistical evidence, however, for interaction on cancers of the mouth (p = 0.28) or larynx (p = 0.95). Among never smokers, heavy drinkers had 9.2 times (95% confidence interval 1.7, 48.5) greater risk of cancers of mouth, pharynx, and supraglottis than never drinkers, with a dose-response trend (p = 0.013) with cumulative consumption. The authors conclude that the interaction occurring in the pharynx between smoking and alcohol on UADT cancers is not uniform, with varying effects depending on the level of smoking exposure. Alcohol may act as both a promoter for tobacco and as an independent risk factor.

Re: Interaction between Tobacco and Alcohol Consumption and the Risk of Cancers of the Upper Aero-Digestive Tract in Brazil. Letter to the editor

The present study aimed to detect possible differences in the data of oral squamous cell carcinomas (OSCC) cases diagnosed in a Dental School in Sao Paulo city over the last 40 years. The records of patients diagnosed as having OSCC between the years 1960 and 2008 were retrieved. The whole period was divided into four time periods. A total of 1,564 cases were reviewed. The variables analyzed were: sex, age, race, anatomical site, lesion duration, and lesion size. The chi-square test was used for statistical analysis. Overall, males were more affected than females (3:1), but when comparing the first and last time periods, the ratio decreased significantly (5.8:1 to 2.8:1). A significant increase in the rate of OSCC in patients over 80 years was observed in the last time periods. The gingiva was the most affected site, but the frequency of lower lip involvement increased in the last time period. Regarding lesion size and duration of symptoms at the time of diagnosis, there was a significant difference between the first and last time periods. Smaller lesions were found and the time of lesion development was shorter in the last few years of the study. These findings support the optimistic view that, in recent years, earlier diagnosis has resulted from early oral cancer detection in Sao Paulo city. (J Oral Sci 52, 267-273, 2010)

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Oral squamous cell carcinoma: an analysis of 1,564 cases showing advances in early detection

Transforming Growth Factor β (TGF-β) is a multifunctional cytokine that plays a role in several biological processes. TGF-β1 is the most abundantly expressed isoform, associated with susceptibility to various diseases, and several polymorphisms have been described in the TGF-β1 gene structure, and some of them have been associated with functional implications. To date, eight single-nucleotide polymorphisms (SNPs) and one deletion/insertion polymorphism have been shown to affect TGF-β1 expression (rs2317130, rs11466313, rs1800468, rs1800469, rs11466314, rs1800471, rs1800470, and rs11466316); some of these interfere with transcriptional regulation by affecting the binding of transcription factors binding, while others interfere with protein production. These polymorphisms have been associated with different types of diseases (i.e., cancers, cardiac diseases, inflammatory diseases, and others) and could therefore be used as susceptibility biomarkers. Since polymorphism clusters are likely to be more reliable than single polymorphisms in this respect, it is hoped that haplotype analysis of TGF-β1 may reveal the genetic basis of disease susceptibility associated with the TGF-β1 gene.

http://www.jle.com/fr/revues/ecn/e-docs/tgf_1_functional_polymorphisms_a_review_309493/article.phtml?tab=download&pj_key=doc_attach_34652

TGF-β1 functional polymorphisms: a review

Oral carcinoma is the sixth most frequent type of cancer in the world and the seventh most common in Brazil (the country with the highest incidence in Latin America). Mean five-year survival remains one of the lowest among the main cancers, thus justifying studies that contribute to the development of preventive strategies. The aim of this study was to compare the epidemiological, clinical, and histological characteristics of 91 patients with oral carcinoma. Mean age was 58.62 ± 10.46 years, and male-to-female ratio was 6.6:1.0 (79 men and 12 women). European descendants predominated with 79 patients (86.8%). Eighty-five individuals (93.4%) smoked and 70 (76.9%) consumed alcohol regularly. Anatomical distribution of tumors was: 27 (29.7%) tongue; 18 (19.8%) floor of mouth; 11 (12.1%) oropharynx; and 11 (12.1%) oral mucosa. Fifty-seven patients (62.6%) presented lymph node involvement and three (3.3%) had distant metastases. Surgery and radiotherapy were used in 43.2% of patients. With the exception of the male/female ratio (which was higher), our data are consistent with previous studies on oral carcinoma patients.

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Oral carcinoma epidemiology in Paraná State, Southern Brazil

Background: A case control association study was carried out to investigate polymorphisms in genes CYP1A1 (3801T>C), GSTM1, and GSTT1 (null genotypes) and oral squamous cell carcinoma (OSCC), including a correlation with some histopathological findings (tumor size, lymph node invasion and degree of tumor differentiation). Patients and Methods: The patients (n=91) and the controls (n=81) were matched by age, sex, ethnicity and smoking habits. The molecular analysis was carried out using Polymerase Chain Reaction-Restrict Length Polymorphisms PCR-RFLP (CYP1A1) and Multiplex-PCR (GSTM1/GSTT1). Results: No association was found for any of the studied genes: CYP1A1 (odds ratio (OR)=1.24; 95% Confidence Interval (CI)=0.67- 2.31), GSTM1 (OR=0.61; CI 95%=0.33-1.11), and GSTT1 (OR=1.24; CI 95%=0.65-2.38). The analysis of combining genotypes also showed lack of association. Comparison with the histopathological findings did not, in general, detect any statistically significant differences. Conclusion: CYP1A1, GSTM1 and GSTT1 polymorphisms do not appear to influence the genetic susceptibility to OSCC or the progression to more advanced stages. Oral squamous cell carcinoma (OSCC) is the most prevalent tumor among head and neck cancer and is a great

Lack of association among polymorphic xenobiotic-metabolizing enzyme genotypes and the occurrence and progression of oral carcinoma in a Brazilian population.

Oral squamous cell carcinoma (OSCC) is a worldwide health problem because it is a great cause of cancer morbidity and mortality. The transforming growth factor-β1 (TGF-β1) is involved in the regulation of numerous immunomodulatory processes. Thus, the aim of this case-control study was to investigate the possible association between the TGF-β1T869C polymorphism and oral cancer. The genomic DNA extracted from peripheral blood of 62 male smoker patients diagnosed with OSCC and 62 smokers without cancer was analysed. The C allele was significantly more prevalent in the oral cancer group than in the controls, and individuals carrying this allele had an estimated 2.73-fold greater relative risk of developing cancer compared with C allele noncarriers (OR = 2.73, 95% CI = 1.19-6.28). Although T allele was not statistically significant among the controls, considering the genotypic analysis, the TT homozygous genotype showed a protector effect in relation to oral cavity cancer (OR = 0.37, 95% CI = 0.16-0.84). Some clinicopathological features were also analysed for genotype distribution, and no significant differences were observed: tumour size (P > 0.70), nodal status (P > 0.10) and tumour stage (P > 0.70). This is the first report of a study assessing the importance of T869C TGF-β polymorphism in oral cancer. It is known that the TGF-β T869C variation results in a Leu10Pro substitution in the signal peptide sequence. Our results suggested that the C allele could increase TGF-β secretion which suppresses antitumour immune responses and may affect the OSCC risk.

Gyl Ramos

Papers

Oral carcinoma epidemiology in Paraná State, Southern Brazil

Lack of association among polymorphic xenobiotic-metabolizing enzyme genotypes and the occurrence and progression of oral carcinoma in a Brazilian population.

Possible association between TGF-β1 polymorphism and oral cancer.