Relationship between mercury levels in blood and urine and complaints of chronic mercury toxicity from amalgam restorations.

AIM: To determine whether patients complaining of oral and medical symptoms perceived to be associated with chronic mercury toxicity have elevated mercury levels in their blood and urine. METHODS: The study group in this audit were 56 patients presenting to an oral medicine unit with complaints perceived to be related to chronic mercury toxicity. Their symptoms and co-morbidity were charted and mercury levels in blood and urine were biochemically tested by atomic absorption spectrophotometry. RESULTS: None had elevated mercury levels in blood or urine above the normal threshold level. Subgroup analysis showed subjects with oral lesions, autoimmune disorders and multiple sclerosis had relatively and significantly higher mercury levels within this cohort, but within the threshold values. When tested by multiple logistic regression adjusted for age and gender, mercury levels in blood or urine, numbers of amalgams were not significant for multiple sclerosis or previously diagnosed autoimmune disease. CONCLUSION: Mercury levels in blood and urine of this cohort of patients with perceived chronic mercury toxicity were within the normal range in accordance with a national laboratory threshold value.

Clinical, pathological, cellular and molecular lesions caused by oral smokeless tobacco--a review.

While carcinogenicity of smokeless tobacco (ST) to humans is well established the oral lesions that precede development of cancer are less well characterized. The clinical appearances of ST-associated lesions are variable. Epidemiological studies show a strong significant association of risk with chronic daily use but population differences are noted because of various commercial products in use. Morphological features observed are some what different to oral lesions caused by smoking and oral dysplasia in ST-associated lesions is less common. Effects of ST on oral keratinocytes observed in vitro include alterations in cell proliferation, apoptosis and activation of inflammatory markers. Genetic aberrations caused by ST include activation of ras, uncommon in smokers but mutational hot spots in p53 encountered are similar to those in smokers.

Incidence of oral and oropharyngeal cancer in United Kingdom (1990-1999) -- recent trends and regional variation.

This study aimed to determine whether the incidence of oral cancer is continuing to rise in the UK and if this varies geographically. A descriptive epidemiological study of oral cancer incidence in 12 UK cancer registries (1990-1999) was undertaken. Poisson regression models were employed to assess trends. There were 32,852 oral cancer cases registered (1990-1999). Statistically significant increases in incidence of 18% and 30% were seen in males and females respectively (p<0.01). The trend was observed in younger (<45 years) and older (45+ years) age groups (p<0.01) with 3.5% and 2.4% average annual increases respectively. These increases were consistent for the majority of regions in the older group. For the younger group the increases in incidence were more rapid and differed geographically. Incidence remains higher in men than women, in older compared with younger groups, and in northern regions. These findings provide evidence of a continuing increase in the burden of oral cancer across the UK.

Tobacco cessation activities of UK dentists in primary care: signs of improvement.

OBJECTIVE: To investigate attitudes and opinions of the members of the British Dental Association towards implementing tobacco cessation strategies in dental practices. DESIGN AND METHOD: Questions about tobacco and tobacco cessation were asked on the September 2002 BDA Omnibus survey. The survey was sent out to a random sample of 1,500 BDA members, excluding retired members, overseas members and students. After two reminder circulations, 870 completed questionnaires were received, giving a response rate of 58%. RESULTS: The survey results revealed good awareness amongst respondents of the health risks of tobacco. One fifth of respondents said that patients had asked them for advice on tobacco cessation. The majority (64%) of respondents stated that they gave advice on tobacco cessation 'fairly regularly' or 'always' (whether asked or not) and 37% of respondents recommended over-the-counter nicotine replacement therapy. Overall, 68% of respondents agreed that offering patients advice about tobacco cessation was the duty of every dentist. The most common barriers to a successful tobacco cessation campaign were perceived to be the amount of time required, lack of reimbursement, lack of training, lack of patient education materials and lack of knowledge of available referral resources. Nearly all respondents (92%) said that their practice was a completely smoke-free environment, and 66% of respondents had never used tobacco. The majority of respondents displayed patient education materials in their practice waiting/reception areas less than 60% of the time, and nearly a quarter (23%) never had them available. The survey revealed that most respondents did not feel particularly well prepared to assist patients in quitting tobacco, but 70% of respondents said they would be willing to cooperate with a campaign to inform all tobacco using patients about the advantages of tobacco cessation. Respondents felt that leaflets for patients, staff training and posters in the practice would contribute to the success of the campaign. CONCLUSION: Members of the dental team are very willing to implement tobacco cessation strategies in the dental practice. Most dentists feel that promotion of tobacco cessation is an important part of the duty of a dentist, but they feel inadequately prepared to deliver such advice. The major barriers to delivering successful tobacco cessation campaigns are the amount of time required, lack of reimbursement, lack of training, lack of patient education materials and lack of knowledge of available referral resources. The majority of dentists have received no training in tobacco cessation strategies. They feel that staff training and free availability of more patient education materials (leaflets, posters, etc) would help promote the success of such a campaign.

Risk factors for oral cancer in newly diagnosed patients aged 45 years and younger: a case-control study in Southern England.

BACKGROUND: This case-control study aimed to identify the risk factors for oral cancer in patients aged 45 years and under. METHODS: Patients were recruited over a 3-year period between 1999 and 2001 from 14 hospitals in the southeast of England, UK. RESULTS: Fifty-three (80%) newly diagnosed patients with squamous cell carcinoma (SCC) of the oral cavity participated. The mean age of cases at diagnosis was 38.5 years (SD = 7.0) and 53% were male. Patients were interviewed about main risk factors of tobacco, alcohol, cannabis and their consumption of fresh fruit and vegetables in the past. Ninety-one matched control patients were also recruited. Odds ratios (ORs) and 95% confidence intervals (CI) were obtained from adjusted conditional logistic analyses. Significantly elevated ORs were evidenced amongst males who had started to smoke under the age of 16 years (OR = 14.3; 95% CI: 1.1-178.8). A significant reduction in risk was also shown for ex-smokers (OR = 0.2; 95% CI: 0.5-0.8). Consumption of alcohol in excess of recommended amounts also produced an eightfold risk in males (OR = 8.1; 95% CI: 1.6-40.1) and over a fourfold risk of oral cancer from the consumption of excessive amounts of alcohol and having ever smoked (OR = 4.4; 95% CI: 1.1-17.7). CONCLUSION: The study shows that the traditional behavioural risk factors are present in younger people diagnosed with oral cancer. The relatively short duration of exposure and the substantial number of cases without any known risk factors, particularly amongst females, however, suggest that factors other than tobacco and alcohol may also be implicated in the development of oral cancer in a proportion of these younger patients.

Prevalence of oral mucosal lesions in alcohol misusers in south London.

BACKGROUND: Information on alcohol-associated oral mucosal lesions (OMLs) and conditions is meagre. A prevalence survey among alcohol misusers in south London was therefore undertaken. METHODS: Six hundred and ninety-three subjects (388 alcohol misusers and 305 alcohol + substance abuse) attending several clinical care facilities in south London between 1994 and 1999 were interviewed on their alcohol and drug habits. A comprehensive oral mucosal examination was performed, and soft tissue lesions found were classified by the clinical criteria of Axéll. RESULTS: Mean age of the sample was 40.5 years. The majority was white (92.6%); of the whites, 29.9% were Celts (i.e. Irish, Scots resident in London). Many subjects reported misusing more than one type of beverage. Two hundred and twenty-seven OMLs were found in 195 subjects (28.1%). The highest prevalences were found for frictional keratosis (8.8%), scar tissue of the lips (4.8%) and candidiasis (3.8%). Angular cheilitis was present in 21 subjects (3.0%). The alcohol-related OMLs detected were three white patches compatible with a diagnosis of leukoplakia and one treated oral carcinoma. No erythroplakias were detected. The differences in prevalence of mucosal lesions in the two groups were not significant (chi(2) = 2.18; P = 0.14). The prevalence of tobacco smoking was high in both study groups. OMLs were found with all four types of beverages consumed, and there was little variation by the units per week consumed. Concurrent use of substances and alcohol did not make a significant difference to the prevalence of OML. In the logistic regression analysis, minority ethnic groups (Black or Asian), smokers, those with a body mass index (BMI) under 20 and beer drinkers had an increased risk of an OML in this group of alcohol misusers. CONCLUSIONS: In comparison with previous oral mucosal screening programmes undertaken in several settings in the UK, the present study has yielded a higher prevalence of oral mucosal diseases and conditions in this risk population. There are several ways in which alcohol could contribute to these detected oral lesions, either directly or indirectly.

Anaemias of oral significance

Anaemia is not a disease in itself. It is a sign of a single or multiple diseases. Anaemia is said to exist when the haemoglobin concentration is below normal for the age and sex of an individual. The synthesis and normal circulatory level of haemoglobin in any given individual depend on factors such as an adequate supply of haemopoietic nutrients, normal functioning of bone marrow, and proper utilization of haemoglobin. Based on these factors anemia can be broadly grouped into three categories: 1. Anaemia due to lack of haemopoietic nutrients (nutritional anemia) 2. Anaemia due to bone marrow dysfunction (aplastic anaemia) 3. Anaemia due to excessive breakdown of red blood cells (haemolytic anaemia) (AU)

Comparison of cell proliferation in the centre and advancing fronts of oral squamous cell carcinomas using Ki-67 index.

The cell proliferation status of 60 oral squamous cell carcinomas from Sri Lankan subjects was examined by immunohistochemistry using the Ki-67 index. A comparison was made between the indices derived from the centre of the tumours and those derived from the invasive fronts of the same tumours. There was a positive correlation between the two indices suggesting a clonal expansion of malignant cells, but the mean index derived for the invasive fronts (29.75 11.64) was significantly higher than the mean index for the body of these tumours (25.65 11.64). Thus, at a given time, more peripheral cells at the invasive front are proliferating and this compartment is likely to be more informative in prognostic and other behavioural studies involving the cell cycle. In squamous carcinomas, increased and uncontrolled cell proliferation at the invasive front may be one feature contributory to the invasion.

Multiple primary tumours following head and neck cancer in southern England during 1961-98.

BACKGROUND: Successful initial treatment of oral and oro-phayngeal cancer has led to the emergence of second primary tumours (SPTs). Population data are meagre. METHODS: Occurrence of multiple primary cancers following a malignancy in a head and neck site was computed using data from a population-based cancer registry covering a population of 14 million. RESULTS: Among 59,958 subjects reported to the registry, 5.5% males and 3.6% females developed a second primary cancer. At the sites studied, a total of 2771 second primary cancers were found, compared with an expected number of 2341. The standardised incidence ratio (SIR) for contracting a new primary cancer was 1.14 (95% CI=1.09-1.19) for men and 1.34 (95% CI=1.24-1.44) for women. There was a significantly increased risk for a second cancer in most of the upper aerodigestive tract sites that are generally regarded as tobacco associated, with an SIR for subsequent oral cancer of 5.56 in men and 15.31 in women. Subjects first detected with a pharyngeal cancer experienced the highest SIR for a subsequent tumour. Excluding tobacco-associated sites, the risk of a subsequent cancer was not significantly raised in either sex (SIR 0.87 (95% CI 0.81-0.93) for men; SIR 0.99 (95% CI 0.90-1.09) for women). CONCLUSIONS: The relative risk for multiple primary cancer was higher in younger subjects, those detected with a head and neck cancer during the 1990s as compared with earlier decades of the study, and among patients who received radiotherapy for their first tumour. By 20 years from the time of the first head and neck cancer, we estimate that approximately 30% of male patients and 20% of female patients will have developed an SPT.

Squamous cell carcinoma of the oral cavity in patients aged 45 years and under: a descriptive analysis of 116 cases diagnosed in the South East of England from 1990 to 1997.

BACKGROUND: there is, currently, much anecdotal and some epidemiological evidence for a rise in oral cancer rates amongst younger individuals, many of whom have had no exposure to traditional risk factors such as tobacco and heavy alcohol use, or at least not the exposure over decades usually associated with this disease. The probity of this assertion and the presence or absence of traditional risk factors needs further evidence. OBJECTIVES: this paper describes the demography and the exposure to potential risk factors amongst a cohort aged 45 years and younger, diagnosed with squamous cell carcinoma of the oral cavity between 1990 and 1997 from the South East of England. MATERIALS AND METHODS: eligible patients registered with a cancer registry were included in this retrospective study. Information was accessed from the database and by a postal questionnaire survey. The self-completed questionnaire contained items about exposure to the following risk factors: tobacco; alcohol; diet; frequency of dental visits and familial cancer. RESULTS AND CONCLUSIONS: this is the largest UK epidemiological study so far to be undertaken on young subjects diagnosed with oral cancer. One-hundred and sixteen cases were recruited representing a response rate of 59%. Slightly over 90% of this cohort were classified as white European. A large proportion of cases (40%) were from social classes I & II suggesting either a true social class difference in young cases versus older oral cancer cases or a possible bias in responders or survivors. Risk factors of tobacco use and excessive alcohol consumption were present in the majority (75%) of patients. Significant differences in the pattern of alcohol consumption were found in female subjects, who were less likely to consume over the recommended amounts of alcohol compared with male subjects. Daily regular fresh fruit and vegetable consumption during the ten year period before cancer diagnosis was recorded to be low. There was a distinct subgroup of cases, 26% of the group, that showed little, if any, exposure to any major risk factors.

Mutations of the cell cycle arrest gene p21WAF1, but not the metastasis-inducing gene S100A4, are frequent in oral squamous cell carcinomas from Sudanese toombak dippers and non-snuff-dippers from the Sudan, Scandinavia, USA and UK.

PCR and direct DNA sequencing methods were used to analyse the prevalence of mutations in exon 2 of the p21waf1 gene in 14 oral squamous cell carcinomas (OSCCs) and 8 non-malignant oral mucosal lesions from Sudanese toombak dippers. For comparison, OSCCs (14 from the Sudan, 16 from Norway, 11 from Sweden, 21 from the USA and 14 from the UK) and non-malignant oral mucosal lesions (3 from the Sudan) from non-snuff-dippers were included. The prevalence of mutations in exons 2 & 3 of the S100A4 gene were analysed in the 14 OSCCs from toombak-dippers and in 25 cases of OSCCs from the control non-snuff-dippers. Of the 14 OSCCs investigated from toombak-dippers, mutations in the p21waf1 exon 2 were found in 43% (6 out of 14), compared to 14% (2 out of 14), 22% (6 out of 27) and 14% (5 out of 35) found in those from non-snuff-dippers from the Sudan, Scandinavia and the USA/UK, respectively. OSCCs from toombak-dippers showed 13 different mutations distributed as 10 (77%) transitions and 3 (23%) transversions. OSCCs from non-snuff-dippers from the Sudan, Scandinavia, the USA and the UK showed 33 different mutations distributed as 14 (42%) transitions and 19 (58%) transversions. In the OSCCs examined, cases with mutations in the p21waf1 also had p53 gene mutations. Only exon 2 of the S100A4 gene was found mutated in 3 cases of OSCCs (one from a toombak-dipper and two from the non-snuff-dippers). The toombak-dipper OSCC had 4 mutations (one transition, 3 transversions), compared to the OSCCs from non-snuff-dippers which showed 3 mutations each (one transition, 2 transversions). All these 3 cases were negative for mutations in the p21waf1 and p53 genes. No mutations of p21waf1 or S100A4 were found in the non-malignant oral mucosal lesions from the snuff-dippers/non-dippers. These findings suggest that; (i) p21waf1, together with p53, is a target gene of oral carcinogenesis in OSCCs from toombak-dippers, with the tobacco specific nitrosamines present in toombak possibly acting as principal carcinogens in these OSCCs; (ii) findings of p21waf1 exon 2 mutations in the OSCCs unrelated to snuff use further demonstrate that this gene may play an important role during the pathogenesis of OSCCs caused by smoked tobacco use; (iii) mutations in the S100A4 gene are rare in OSCCs, but appears to be complementary to p21waf1 and p53 mutations. Since molecular analysis of OSCCs can provide clues to endogenous or environmental factors contributing to the high risk of OSCCs, further analysis of the role of the p21waf1 gene mutations as a biomarker of malignant transformation, which is linked to the p53 gene, is necessary, especially in habitual users of toombak from the Sudan.

Epithelial cell proliferation in oral lichen planus.

Although the pathogenesis of oral lichen planus (OLP) is not clear, a small proportion of cases with OLP are reported to transform to cancer. We examined the epithelial cell proliferation status of OLP to relate the labelling index to microscopic features surveyed routinely in pathology. Mucosal biopsies obtained from 44 cases diagnosed with OLP with an intact oral epithelium and 10 normal control specimens from Japanese subjects were immunohistochemically stained with MIB and p53 antibodies. The Ki67 labelling index (LI) was significantly higher in OLP compared with normal controls. A particularly large number of OLP lesions (64%) were p53 positive. No association was, however, found with p53 expression and the Ki67 LI. Atrophic and flat epithelia had a quantitatively higher LI, which did not significantly differ from acanthotic biopsies. Increased cell proliferation in OLP is likely to be a secondary phenomenon due to the damage inflicted on keratinocytes by infiltrating mononuclear cells in the submucosa.

Oral manifestations of an HIV positive cohort in the era of highly active anti-retroviral therapy (HAART) in South London.

BACKGROUND: Human Immunodeficiency Virus (HIV) infection is associated with oral manifestations of diagnostic and prognostic importance. With the advent of Highly Active Anti-retroviral Therapy (HAART) there is anecdotal evidence to suggest that the prevalence of oral lesions has declined. The number of prevalence studies, carried out in the era of HAART is, however, meagre. Our aim was to study the prevalence of the oral manifestations of HIV in a population, predominantly on HAART, attending a Genito-Urinary Medicine Centre in South London. METHODS: This cross sectional study included 203 adult volunteers, comprising 76% males and 24% females. One third of the subjects were from the predominantly African or Afro- Caribbean ethnic minority groups resident in London. The relationship between the prevalence of oral lesions and demographic variables, therapeutic regimes, viral load and CD4 counts were evaluated. RESULTS: One hundred (49%) of the patients had no detectable oral lesions. Oral lesions detected most frequently included oral hairy leukoplakia (9.9%), HIV associated periodontal diseases (9.9%) and oral candidiasis (4.9%). Three subjects had multiple papillomatous growths. Most cases (n = 17/20) of oral hairy leukoplakia were in individuals with a detectable (> 400 copies/ml) plasma RNA viral load. The majority (n = 8/10) of our patients with oral candidiasis had a plasma RNA viral load > 10,000 copies/ml and half (n = 5/10) had a CD4 count < 200 cells/mm3. Logistic regression analysis suggested that the presence of an oral lesion was not associated with any demographic features except for periodontal diseases which were associated with tobacco smoking (P = 0.023). CONCLUSIONS: The prevalence of so called 'strongly associated' oral lesions of HIV is low in this South London HIV-infected population on HAART, and the relative frequency is different from that cited in the literature from the pre-HAART era. The oral lesions detected were found mostly in people with low CD4 counts and high HIV-1 RNA viral loads, suggesting they were very immunocompromised, not on, or declining therapy, or that their therapy was failing.