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Biomedical subjects

K A Warnakulasuriya

Publications and source records attributed to K A Warnakulasuriya.

At least 19 recordsLinked to original sources

Risk factors for squamous cell carcinoma of the oral cavity in young people--a comprehensive literature review.

There have been several reports of a rising incidence of oral cancer from many parts of the world. Although it is well known that oral cancer increases with age, recent trends for a rising incidence particularly relates to cancer of the tongue and mouth in young males. This review critically examines 46 publications devoted to oral cancer in the young adult. Most studies suggest that 4-6% of oral cancers now occur at ages younger than 40 years. Several studies examining risk factors for oral cancer in the young provide evidence that many younger patients have never smoked or consumed alcohol, which are recognised risk factors in older groups, or that duration of exposure may be too short for malignant transformation to occur. Information on many aspects of aetiology for this disease in the young implicating occupational, familial risk, immune deficits and virus infection are meagre. The spectrum of genetic abnormality disclosed is similar to older patients, there is paucity of specific studies involving younger cohorts, but predisposition to genetic instability has been hypothesised as a likely cause. Conflicting evidence is also reported on the sex distribution and outcome compared with older patients. Much work is required to understand the caveats related to global demography, risk factors and their diagnostic and prognostic markers for this disease which might be considered a disease distinct from that occurring in older patients.

Adolescent↗

Copper stimulates human oral fibroblasts in vitro: a role in the pathogenesis of oral submucous fibrosis.

Copper is implicated in the pathogenesis of several fibrotic disorders. Areca nut has been shown to have a high copper content and areca chewing is associated with oral submucous fibrosis (OSF). The effects of copper on human oral fibroblasts were investigated in vitro. Human oral fibroblasts were incubated with copper chloride (CuCl2) at concentrations ranging from 0.01 microM to 500 microM for 24 h, and in vitro cell proliferation was assayed by incorporation of tritiated-thymidine; soluble and non-soluble collagen synthesis was assayed using tritiated-proline. Addition of copper chloride at concentrations ranging from 0.1 microM to 50 microM increased the collagen synthesis by the oral fibroblasts compared with growth without copper (P<0.05). The addition of copper chloride neither increased the synthesis of non-collagenous proteins by the fibroblasts nor influenced their proliferation rate. We conclude that copper upregulates collagen production in oral fibroblasts. This appears to be concentration dependent, with peak collagen synthesis at 50 microM CuCl2. These in vitro results taken together with the recent findings of copper in oral biopsies from OSF subjects support the hypothesis that copper in areca nut acts as a mediator of OSF.

Areca↗

Action on smoking--opportunities for the dental team.

In 1998, the UK government published a White Paper outlining a comprehensive range of measures to reduce smoking rates across the population. In the same year a detailed overview of the evidence base for smoking cessation activities within the NHS was published. Both these documents provide useful information for health professionals interested in developing their roles in smoking cessation and prevention. An increased risk for the development of oral malignancies and a susceptibility for the breakdown of periodontal tissues are the most significant effects of smoking on the mouth. This paper aims to highlight how dentists and their team members can become actively involved in efforts to reduce smoking. Opportunities at both a clinical and public health level are considered.

Dental Staff↗

Predictors of tobacco and alcohol consumption and their relevance to oral cancer control amongst people from minority ethnic communities in the South Thames health region, England.

The purpose of this study was to examine the determinants of the health behaviour of ethnic groups in relation to alcohol and tobacco use. A cross-sectional questionnaire survey was carried out using network sampling amongst community groups in the South Thames region of the United Kingdom. Self-classified ethnic groups were identified: Black-African; Black-Caribbean; Indian; Pakistani; Bangladeshi and Chinese/Vietnamese. A total of 1113 people were recruited in the study. In all of the ethnic groups, men were more likely than women to smoke tobacco. Chewing of pan and tobacco was common in the South Asian communities and alcohol consumption was high among the Black-Caribbean group. Those factors were predicted by education, employment, gender and being born in the UK. It is important to examine the determinants of such risk behaviours in order to aid appropriate targeting of health promotion interventions, particularly those related to cancer control.

Adult↗

Raised tissue copper levels in oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a well-recognised-potentially malignant condition of the oral cavity associated with areca nut chewing. Areca nut has been shown to have a high copper content compared to other commonly eaten nuts, and chewing areca nut for 5-30 min significantly increases soluble copper in whole mouth fluids. Our aims were to determine if tissue and serum concentrations of copper were raised in patients with OSF as a result of chewing areca nut. A panel of buccal mucosal biopsies from patients with OSF from Nagpur, India, was used to measure the tissue concentrations of copper by mass absorption spectrometry (MAS). By MAS, the mean tissue copper level was 5.5+/-2.9 microg/g in the OSF specimens (n=11) compared with 4+/-1.9 microg/g in the non-areca chewing controls (n=7) (P=0.2). Energy dispersive x-ray microanalysis (EDX) was used to identify the presence and distribution of the metal element. EDX showed distinct peaks corresponding to copper (Kalpha 8.04 keV; Kbeta, 8.91 keV) in the epithelium (21/23) and in the connective tissue (17/23) of the OSF specimens compared to spectra obtained from control oral biopsies from non-areca chewing subjects (n=7). These findings were confirmed by secondary ion mass spectrometry (SIMS) analysis in a small number of samples. Serum copper (17.23+/-1.80 pmol/l), caeruloplasmin (0.32+/-0.04 g/l) levels and urinary copper (0.52+/-0.26 micromol/l) in OSF patients (n=14) were within the laboratory reference ranges. The finding of copper in OSF tissue supports the hypothesis of copper as an initiating factor in OSF, playing a role in stimulating fibrogenesis by the upregulation of lysyl oxidase activity.

Adolescent↗

Prevalence and incidence of oral lesions--the changing scene.

A range of oral mucosal and periodontal lesions is associated with HIV infection and HIV disease progression. These are often symptomatic and require treatment in themselves, and also have a diagnostic and prognostic role in the management of the underlying HIV disease. These lesions have been broadly divided into: (a) those strongly associated with HIV such as oral candidoses, oral hairy leukoplakia and Kaposi's sarcoma; (b) those less strongly associated such as swellings of the major salivary glands; and (c) those least commonly associated such as recurrent aphthous ulcers. Overall the prevalence and severity of these lesions inversely correlate with the level of immunosuppression. With the passage of time, there has been improved understanding of the disease pathogenesis resulting in the development of new drugs to combat this infection. Medication has changed from monotherapy to current triple combination therapy (Highly Active Anti-Retroviral Therapy). This review looks at the impact of changing therapy on the prevalence of the various oral lesions associated with HIV. It finds a decrease in the prevalence of the oral lesions in the era of combination therapy as compared to earlier periods. It also shows a change in the types of lesions which predominate with those previously placed amongst the strongly associated lesions no longer being predominant in the era of combination therapy where such treatment is available.

AIDS-Related Opportunistic Infections↗

An alarming lack of public awareness towards oral cancer.

OBJECTIVE: To determine public awareness and knowledge of oral cancer in Great Britain. DESIGN: The respondents were selected according to a systematic probability sample designed to be representative of all adults in Great Britain (GB). The overall design was similar to previous omnibus surveys carried out by National Opinion Poll (NOP). The survey was carried out in ten regions of GB in September 1995 and was commissioned by the Health Education Authority (HEA). SUBJECTS AND METHODS: A random sample of 1,894 members of the public over the age of 16 years were asked in face-to-face interviews their knowledge relating to cancer, with particular reference to oral cancer, its causes and those at high risk and general attitudes to cancer. RESULTS: Oral cancer was one of the least heard of cancers by the public with only 56% of the participants being aware, whereas 96% had heard of skin cancer, 97% lung cancer and 86% cervical cancer. There was a 76% awareness of the link between smoking and oral cancer but only 19% were aware of its association with alcohol misuse. Whereas 94% agreed that early detection can improve the treatment outcome, a disheartening 43% believed that whether a person developed a cancer or not was a matter of chance and therefore was unavoidable. CONCLUSIONS: This survey highlights a general lack of awareness among the public about mouth cancer and a lack of knowledge about its causation especially the excess risk associated with alcohol. RECOMMENDATIONS: There is a clear need to inform and educate the public in matters relating to the known risk factors associated with oral cancer. A media campaign informing the public about oral cancer is clearly required. The need for the reduction in the incidence of oral cancer should be included in 'Our healthier nation' targets. An overall health promotion strategy to reduce cancers should include oral cancer as a priority. In addition the European Code against Cancer which aims to improve prevention, the early detection of oral cancer and the necessity for fast track referral should be made more widely known. Recognition of oral cancer in local strategies for oral health should be encouraged.

Adolescent↗

Cancer of mouth, pharynx and nasopharynx in Asian and Chinese immigrants resident in Thames regions.

Studies on migrants can generate important clues on the etiology of cancer. The purpose of the present study was to determine the relationship between ethnic origin and the incidence of oral and pharyngeal cancers among residents of the Thames regions in southern England. Records from the Thames Cancer Registry during the period 1986-91 were examined and south Asians and Chinese ethnic immigrants flagged using their place of birth and names. Computation of relative incidence among head and neck cancers (n = 7222) showed that oral cancer was significantly higher among Asians (95/232 = 40.9%) and nasopharyngeal cancer among Chinese (45/67 = 67.2%). Some differences in the intra-oral site of cancer and ethnic origin were noted. The ethnic migrants were significantly younger (Asians 51.6 +/- 34.8 years, Chinese 47.6 +/- 14.8 years) compared to the rest of the population (64.8 +/- 15.6 years) at the time of cancer diagnosis (p = 0.0) but no significant differences were found for the stage of presentation. The mean survival period for a cancer of the head and neck was 2.2 years and significant differences in cumulative rates of survival were noted among the three groups studied (p = 0.003). A strong correlation was noted between the incidence of oral cancer and local authorities with a high percentage of Asian residents. The south Asian and Chinese ethnic minorities constitute important high risk groups for oral and nasopharyngeal cancer, for whom targeted prevention is indicated.

Adult↗

The upregulation of lysyl oxidase in oral submucous fibrosis and squamous cell carcinoma.

Lysyl oxidase (LO) takes part in the initial steps of converting soluble monomers of collagen and elastin into insoluble fibres in the extracellular matrix. We have studied the immunolocalization of LO as a marker of fibrogenesis in oral submucous fibrosis (OSF). Oral biopsies from 13 subjects with OSF, 6 with histologically confirmed squamous cell carcinoma (SCC) arising in OSF and 10 SCC nonrelated to OSF, were examined. Strong positive staining was observed in 7/13 OSF samples in the cytoplasmic processes of fibroblasts and extracellularly in the upper third of the lamina propria. Furthermore, LO was found to co-localize in the areas stained strongly for collagen and elastin by histochemical stains. Examination of SCC tissues showed localization of LO adjacent to invading epithelial islands as evidence of a stromal reaction both in carcinomas arising from OSF and in SCC from non-OSF cases. These findings suggest that upregulation of LO may be an important factor in the pathogenesis of OSF and in the early stromal reaction of oral cancer.

Carcinoma, Squamous Cell↗

Dentists and oral cancer prevention in the UK: opinions, attitudes and practices to screening for mucosal lesions and to counselling patients on tobacco and alcohol use: baseline data from 1991.

OBJECTIVE: To investigate the opinions, attitudes and practices towards oral cancer prevention among UK dentists as a baseline from which to measure the need for continuing education efforts in this area. DESIGN AND METHOD: Postal questionnaire survey carried out in August 1991. A questionnaire with 13 test items was piloted at continuing education courses then distributed to all subscribers of the British Dental Journal with a postage paid return envelope. The aspects inquired into were recent attempts by dentists at updating their knowledge on oral cancer, their practical approaches to screening for oral mucosal diseases and follow-up actions after oral screening, their questions to patients regarding the major risk factors for oral cancer, their efforts towards behavioural counselling for patients and any constraints felt or experienced in this regard. RESULTS: The questionnaire was circulated to 15,836 dentists. The response rate of 16% was poor but due to the many dentists circulated, 2519 responses were available for analysis. This large sample, though presumptively biased towards those interested in professional matters, showed an encouraging 84% claiming to perform screening of the oral mucosa routinely. Among these, 74% reported referral of screen detected cases to a hospital for further attention and only 4% would adopt a wait and see policy. Disturbingly, half of the respondents did not enquire about risk habits related to oral cancer and, among the other half who claimed to make such enquiries, only 30% routinely provided brief health education advice concerning these. Seventy-one percent agreed that giving advice against tobacco use is desirable but major constraints were identified, notably a lack of training, and frustration regarding patient compliance. There was even greater reluctance on the part of the respondents to enquire into the alcohol use of their patients and to provide advice on alcohol moderation. CONCLUSIONS: Most of this large but unrepresentative sample of UK dentists were carrying out screening of the oral mucosa as a part of their prevention activities in 1991. However, the survey indicated a considerable need for improvement in the manner and extent of provision of health advice in respect of the major risk factors for oral cancer: such a substantial need amongst the presumptively better motivated implies that the need amongst the practitioner population at large is even greater.

Alcohol Drinking↗

A smoking cessation programme conducted through dental practices in the UK.

OBJECTIVES: To assess the feasibility of using primary care dentists and the dental team providing smoking cessation advice in practice. DESIGN: A prospective study to examine the success of a smoking cessation programme. SETTING: 54 primary care dental practices in the UK. METHOD: Training and educational materials were supplied to members of the dental team and to potential recruits smoking 10 or more cigarettes a day. Recruitment was over 6 months and subjects were followed up for 9 months. In addition to dentists' counselling, nicotine patches were made available, on request, at cost price. Salivary cotinine assay was used for validation of smoking levels at initial counselling and 9 months after recruitment. RESULTS: 54 practices were enrolled but only 22 recruited patients. Records of 154 eligible patients were evaluated. Compliance to attend follow up clinics was poor--only 74 reported at 9 months. Among them 17 (11%) were successful in giving-up tobacco for 9 months as validated by patient histories and salivary cotinine assay. A large variation performance of the dental practices was noted. CONCLUSIONS: Motivated dentists with staff support and access to information on smoking counselling are able to contribute to tobacco control measures in the community. The success of this programme closely parallels those reported in general medical practice settings. In view of the very considerable attrition rates found at all levels of the programme in the present study and the uneven performance of the participating practices the quit rate reported here may not accurately reflect what could be achieved in an individual primary care setting.

Adult↗

A comparison of the management of potentially malignant oral mucosal lesions by oral medicine practitioners and oral & maxillofacial surgeons in the UK.

This study describes the results of a survey undertaken to assess the management of potentially malignant oral mucosal lesions by oral medicine practitioners and compares their approach with that of oral & maxillofacial surgeons that we have previously described. Significant differences were noted between the two groups in the use of photography to document the lesions and in the use of certain special investigations, which included measurement of serum iron, serum ferritin, serum Vit B12, red cell folate and candidal isolation. The groups also varied in the perceived importance of the age of the patient and anatomical site of the lesion when deciding on the need for further biopsy. There was also significant variation in the use of certain treatment modalities, including excising non-dysplastic and severely dysplastic/carcinoma in-situ lesions and eliminating trauma when treating mild/moderately dysplastic and severely dysplastic/carcinoma in-situ lesions. Significant differences in the frequency and duration of follow-up were noted for non-dysplastic lesions. Finally, the two groups differed significantly when asked to rank the perceived importance of certain factors (the histopathology of the most recent biopsy and the anatomical site of the lesion) when deciding the need to follow-up. Possible reasons for the variation are discussed.

Age Factors↗

Characterization of an amorphous deposit in the lamina propria in oral snuff users in the Sudan as collagen.

Histological and ultrastructural features of 25 oral snuff dipper's lesions with distinctive subepithelial hyaline deposits were investigated. Periodic acid-Schiff reaction with and without diastase digestion demonstrated the presence of glycogen and other carbohydrates, but histochemical stains for normal collagen, elastin and fibrin showed a weak variable reactivity of the deposit. Although in 7/25 cases the deposit was in close proximity to labial salivary glands and on occasions ducts were found within the deposit, the presence of mucin was not a consistent feature. Congo red staining and immunohistochemical investigation with an anti-amyloid antibody did not support the previous contention that such deposits were amyloid in nature. Immunohistochemically, collagen antibodies also provided negative results, but ultrastructural features of three biopsies studied suggest that the bulk of this deposit is made up of collagen, as typical cross-striated fibrils were found. The pathogenesis of this deposit could therefore be interpreted as over-production and/or reduced turnover of collagen by resident fibroblasts, which is further altered by the ingredients of toombak. The deposit does not appear to be a secretory product.

Adult↗

p53 expression in oral precancer as a marker for malignant potential.

The potential of p53 protein expression as a marker for determining which oral precancerous lesions may transform to malignancy with time was assessed. We compared the p53 expression in archival formalin-fixed, paraffin-embedded tissues from 22 baseline biopsies of precancerous lesions that transformed to cancer in 4-25 years against that in 68 similar lesions that did not transform over the same time period. Twenty-nine percent of precancers that transformed were p53-positive at baseline, compared to 31% of the biopsies that did not transform to malignancy. When examined by immunohistochemical methods p53 expression failed to detect potential malignant status of oral precancer. Non-specificity of the assay may account for this result but overexpression of p53 due to DNA damage by tobacco/betel-quid in non-progressive lesions needs further study. Nine precancerous lesions became p53-immunoreactive from precancer to cancer. This may suggest p53 overexpression peaks close to the time of transition from precancer to cancer rather than early in the natural history of oral precancer.

Areca↗

Relationship of p53 overexpression to other cell cycle regulatory proteins in oral squamous cell carcinoma.

Aberrations of the p53 gene and the overexpression of its protein are described in a variety of neoplasms, including oral and other head and neck cancers. Here we report the association of p53 (over)expression with a downstream cell cycle inhibitor p21/waf 1 in oral squamous cell carcinoma (SCC). The loss of expression of p16 and p27, two other cyclin-dependent kinase (cdk) inhibitors, was also examined. In this panel of tumours, 10/24 carcinomas were p53-immunopositive. Heterogeneous expression of p21 and p27 was seen in 10/24 SCC and 9/16 SCC, respectively, and this was not correlated to p53 status. The expression of p21 and p27 in these SCCs suggests the existence of mechanisms by which some growing tumour cells may tolerate these cell cycle inhibitors; eight SCCs lacked expression of both inhibitors but only two of these cancers overexpressed p53, suggesting that accumulation of p21/p27 can be independent of the functional status of the p53 gene. Data do not support a clear example of a phenotype that shows an overexpression of p53 with downregulation of p21 or p27 leading to cell cycle alterations. Furthermore, only three SCCs were p16-negative and p53-positive. This suggests that these two tumour suppressors may act in separate pathways.

Adult↗

p53 aberrations in oral submucous fibrosis and oral squamous cell carcinoma detected by immunocytochemistry and PCR-SSCP.

An archival series of oral biopsies from Karachi, Pakistan, consisting of 21 cases of oral submucous fibrosis (OSF) and 27 cases of squamous cell carcinoma (SCC), of which 6 had arisen from OSF, were used to examine the aberrations in the structure and expression of the p53 tumour suppressor gene. The PCR-SSCP method was used for mutation analysis of exons 2-9, and (over)expression of p53 protein was detected by immunocytochemistry using monoclonal antibody DO 7. Positive immunostaining was observed in 15/20 (75%) of OSF specimens, 3/6 (50%) of SCC arising from OSF and 14/21 (67%) of SCC not arising from OSF. Mobility shifts in SSCP indicative of a mutation in p53 or loss of heterozygosity (deletion of a band) were seen in 13/21 cases of OSF and 15/27 cases of SCC. There was concordance between immunocytochemistry and SSCP results in a majority (33/48) of samples. Though the number of analysed SCC cases arising from OSF was limited, the results suggest that p53 mutation/protein stabilisation may play a part in the pathogenesis of OSF and its progression to SCC.

Adolescent↗

A survey of consultants treating upper aerodigestive tract cancer in the UK.

A study was undertaken to determine the current service provision for the treatment of upper aerodigestive tract (UAT) cancers in the UK. A postal questionnaire was sent to all consultant members of relevant specialist societies, with 1041 (74%) responding. Treatment of UAT cancer is widely dispersed with over 900 consultants from five major disciplines treating, on average, less than 10 cases per year. There were few regional or provider differences in the facilities and services available and in processes used for assessing patients. There is little systematic collection of data for audit or research and some consultants do not record stage. The involvement of other disciplines in the assessment process, use of joint clinics, counselling, specialist nursing and therapy services appears to be low. There is a need for rationalisation of head and neck cancer services; for more systematic collection of data for audit and research and for improvements in the use of joint clinics and support services.

Cancer Care Facilities↗