The role of primary healthcare professionals in oral cancer prevention and detection

AIM: To investigate current knowledge, examination habits and preventive practices of primary healthcare professionals in Scotland, with respect to oral cancer, and to determine any relevant training needs. SETTING: Primary care. METHOD: Questionnaires were sent to a random sample of 357 general medical practitioners (GMPs) and 331 dental practitioners throughout Scotland. Additionally, focus group research and interviews were conducted amongst primary healthcare team members. RESULTS: Whilst 58% of dental respondents reported examining regularly for signs of oral cancer, GMPs examined patients' mouths usually in response to a complaint of soreness. The majority of GMPs (85%) and dentists (63%) indicated that they felt less than confident in detecting oral cancer, with over 70% of GMPs identifying lack of training as an important barrier. Many practitioners were unclear concerning the relative importance of the presence of potentially malignant lesions in the oral cavity. A high proportion of the GMPs indicated that they should have a major role to play in oral cancer detection (66%) but many felt strongly that this should be primarily the remit of the dental team. CONCLUSION: The study revealed a need for continuing education programmes for primary care practitioners in oral cancer-related activities. This should aim to improve diagnostic skills and seek to increase practitioners' participation in preventive activities

Diagnostic aids in the screening of oral cancer

The World Health Organization has clearly indentified prevention and early detection as major objectives in the control of the oral cancer burden worldwide. At the present time, screening of oral cancer and its pre-invasive intra-epithelial stages, as well as its early detection, is still largely based on visual examination of the mouth. There is strong available evidence to suggest that visual inspection of the oral mucosa is effective in reducing mortality from oral cancer in individuals exposed to risk factors. Simple visual examination, however, is well known to be limited by subjective interpretation and by the potential, albeit rare, occurrence of dysplasia and early OSCC within areas of normal-looking oral mucosa. As a consequence, adjunctive techniques have been suggested to increase our ability to differentiate between benign abnormalities and dysplastic/malignant changes as well as to identify areas of dysplasia/early OSCC that are not visible to naked eye. These include the use of toluidine blue, brush biopsy, chemiluminescence and tissue autofluorescence. The present paper reviews the evidence supporting the efficacy of the aforementioned techniques in improving the identification of dysplastic/malignant changes of the oral mucosa. We conclude that available studies have shown promising results, but strong evidence to support the use of oral cancer diagnostic aids is still lacking. Further research with clear objectives, well-defined population cohorts, and sound methodology is strongly required

Long-term outcome and patterns of failure in patients with advanced head and neck cancer

<p>Abstract</p> <p>Purpose</p> <p>To access the long-time outcome and patterns of failure in patients with advanced head and neck squamous cell carcinoma (HNSCC).</p> <p>Methods and materials</p> <p>Between 1992 and 2005 127 patients (median age 55 years, UICC stage III n = 6, stage IV n = 121) with primarily inoperable, advanced HNSCC were treated with definite platinum-based radiochemotherapy (median dose 66.4 Gy). Analysed end-points were overall survival (OS), disease-free survival (DFS), loco-regional progression-free survival (LPFS), development of distant metastases (DM), prognostic factors and causes of death.</p> <p>Results</p> <p>The mean follow-up time was 34 months (range, 3-156 months), the 3-, 5- and 10-year OS rates were 39%, 28% and 14%, respectively. The median OS was 23 months. Forty-seven patients achieved a complete remission and 78 patients a partial remission. The median LPFS was 17 months, the 3-, 5- and 10-year LPFS rates were 41%, 33% and 30%, respectively. The LPFS was dependent on the nodal stage (p = 0.029). The median DFS was 11 months (range, 2-156 months), the 3-, 5- and 10-year DFS rates were 30%, 24% and 22%, respectively. Prognostic factors in univariate analyses were alcohol abuse (n = 102, p = 0.015), complete remission (n = 47, p < 0.001), local recurrence (n = 71, p < 0.001), development of DM (n = 45, p < 0.001; median OS 16 months) and borderline significance in nodal stage N2 versus N3 (p = 0.06). Median OS was 26 months with lung metastases (n = 17). Nodal stage was a predictive factor for the development of DM (p = 0.025). Cause of death was most commonly tumor progression.</p> <p>Conclusions</p> <p>In stage IV HNSCC long-term survival is rare and DM is a significant predictor for mortality. If patients developed DM, lung metastases had the most favourable prognosis, so intensified palliative treatment might be justified in DM limited to the lungs.</p

A comparative analysis of toluidine blue with frozen section in oral squamous cell carcinoma

Background:Surgical excision of the primary tumor with safe margins remains the mainstay of treatment for oral cavity squamous cell carcinoma (OSCC). The standard of care for assessment of intraoperative margins is frozen section histopathology. Unfortunately the facility is not available at most centers in limited resource countries. Toluidine blue, a metachromatic dye, has been well described in clinical identification of malignant and premalignant lesion in the oral cavity. Considering this we decided to explore intraoperative use of toluidine blue staining, in comparison with frozen sections, for the assessment of tumor-free margins. Methods: After obtaining clearance from the in-house ethical review committee, a prospective study was conducted at Aga Khan University Hospital, Karachi, from August 15, 2009 to March 14, 2010. A sample of 56 consenting Patients with biopsy-proven OSCC were included in the study, giving us 280 tumor margins. Margins were analyzed using toluidine blue staining and frozen section histopathology. A receiver operator curve (ROC) was then applied to compare assessment of margin status by toluidine blue and frozen section. Results: Of the 280 examined margins 11 stained positive with toluidine blue, three were positive on frozen section biopsy, and three were positive on final histopathology. Toluidine blue staining had sensitivity and specificity of 100% and 97%, respectively. The diagnostic accuracy of toluidine blue was found to be 97.1% with a positive predictive value (PPV) of 27.2% and a negative predictive value (NPV) of 100%. Conclusions: Toluidine blue can be used as an effective screening modality for the assessment of intraoperative margins in resource limited environments and reducing the number of frozen section biopsies performed. Further by providing real-time clinical information within minutes it can reduce indirect costs such as operating room time. It may also be used as an ad hoc for frozen section biopsies where frozen section facilities are available

Chromosomal aberrations and aneuploidy in oral potentially malignant lesions: distinctive features for tongue

<p>Abstract</p> <p>Background</p> <p>The mucosae of the oral cavity are different at the histological level but appear all equally exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia may develop giving rise to Oral Potentially Malignant Lesions (OPMLs), which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs). Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs) in the OPMLs from different oral anatomical subsites.</p> <p>Methods</p> <p>Samples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM) in order to determine the relative DNA content expressed by the DNA index (DI). Additionally, array-Comparative Genomic Hybridization (a-CGH) analysis was performed on DNA obtained from diploid nuclei suspensions directly. When aneuploid nuclei were detected, these were physically separated from diploid nuclei on the base of their DI values by means of a DNA-FCM-Sorter in order to improve the a-CGH analysis.</p> <p>Results</p> <p>Tongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites.</p> <p>Conclusions</p> <p>We suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this hypothesis should be validated in a prospective clinical study.</p

Exciting new advances in oral cancer diagnosis: avenues to early detection

The prognosis for patients with oral squamous cell carcinoma remains poor in spite of advances in therapy of many other malignancies. Early diagnosis and treatment remains the key to improved patient survival. Because the scalpel biopsy for diagnosis is invasive and has potential morbidity, it is reserved for evaluating highly suspicious lesions and not for the majority of oral lesions which are clinically not suspicious. Furthermore, scalpel biopsy has significant interobserver and intraobserver variability in the histologic diagnosis of dysplasia. There is an urgent need to devise critical diagnostic tools for early detection of oral dysplasia and malignancy that are practical, noninvasive and can be easily performed in an out-patient set-up. Diagnostic tests for early detection include brush biopsy, toluidine blue staining, autofluorescence, salivary proteomics, DNA analysis, biomarkers and spectroscopy. This state of the art review critically examines these tests and assesses their value in identifying oral squamous cell carcinoma and its precursor lesions

The relation between smokeless tobacco and cancer in Northern Europe and North America. A commentary on differences between the conclusions reached by two recent reviews

<p>Abstract</p> <p>Background</p> <p>Smokeless tobacco is an alternative for smokers who want to quit but require nicotine. Reliable evidence on its effects is needed. Boffetta et al. and ourselves recently reviewed the evidence on cancer, based on Scandinavian and US studies. Boffetta et al. claimed a significant 60–80% increase for oropharyngeal, oesophageal and pancreatic cancer, and a non-significant 20% increase for lung cancer, data for other cancers being "too sparse". We found increases less than 15% for oesophageal, pancreatic and lung cancer, and a significant 36% increase for oropharyngeal cancer, which disappeared in recent studies. We found no association with stomach, bladder and all cancers combined, using data as extensive as that for oesophageal, pancreatic and lung cancer. We explain these differences.</p> <p>Methods</p> <p>For those cancers Boffetta et al. considered, we compared the methods, studies and risk estimates used in the two reviews.</p> <p>Results</p> <p>One major reason for the difference is our more consistent approach in choosing between study-specific never smoker and combined smoker/non-smoker estimates. Another is our use of derived as well as published estimates. We included more studies, and avoided estimates for data subsets. Boffetta et al. also included some clearly biased or not smoking-adjusted estimates. For pancreatic cancer, their review included significantly increased never smoker estimates in one study and combined smoker/non-smoker estimates in another, omitting a combined estimate in the first study and a never smoker estimate in the second showing no increase. For oesophageal cancer, never smoker results from one study showing a marked increase for squamous cell carcinoma were included, but corresponding results for adenocarcinoma and combined smoker/non-smoker results for both cell types showing no increase were excluded. For oropharyngeal cancer, Boffetta et al. included a markedly elevated estimate that was not smoking-adjusted, and overlooked the lack of association in recent studies.</p> <p>Conclusion</p> <p>When conducting meta-analyses, all relevant data should be used, with clear rules governing the choice between alternative estimates. A systematic meta-analysis using pre-defined procedures and all relevant data gives a lower estimate of cancer risk from smokeless tobacco (probably 1–2% of that from smoking) than does the previous review by Boffetta et al.</p

Identification of mutations in the PYRIN-containing NLR genes (NLRP) in head and neck squamous cell carcinoma

Head and Neck Squamous Cell Carcinoma (HNSCC) encompasses malignancies that arise in the mucosa of the upper aerodigestive tract. Recent high throughput DNA sequencing revealed HNSCC genes mutations that contribute to several cancer cell characteristics, including dysregulation of cell proliferation and death, intracellular proinflammatory signaling, and autophagy. The PYRIN-domain containing NLR (Nucleotide-binding domain, Leucine rich Repeats - containing) proteins have recently emerged as pivotal modulators of cell death, autophagy, inflammation, and metabolism. Their close physiologic association with cancer development prompted us to determine whether mutations within the NLRP (PYRIN-containing NLR ) gene family were associated with HNSCC genome instability and their clinicopathologic correlations. Catastrophic mutational events underlie cancer cell genome instability and mark a point-of-no-return in cancer cell development and generation of heterogeneity. The mutation profiles of 62 patients with primary conventional type HNSCC excluding other histologic variants were analyzed. Associations were tested using Fisher's Exact test or Mann-Whitney U test. Mutations in NLRP were associated with elevated genome instability as characterized by higher mutation rates. Clinically, NLRP mutations were more frequently found in HNSCC arising in the floor of mouth (50.0%) in comparison with HNSCC at other head and neck locations (14.8%). These mutations were clustered at the leucine rich repeats region of NLRP proteins, and affected NLRP genes were mostly localized at chromosomes 11p15.4 and 19q13.42-19q13.43. Twenty novel NLRP mutations were identified in HNSCC, and mutations in this group of genes were correlated with increased cancer cell genome mutation rates, and such features could be a potential molecular biomarker of HNSCC genome instability. © 2014 Lei et al

Global burden of disease due to smokeless tobacco consumption in adults : analysis of data from 113 countries

BACKGROUND: Smokeless tobacco is consumed in most countries in the world. In view of its widespread use and increasing awareness of the associated risks, there is a need for a detailed assessment of its impact on health. We present the first global estimates of the burden of disease due to consumption of smokeless tobacco by adults. METHODS: The burden attributable to smokeless tobacco use in adults was estimated as a proportion of the disability-adjusted life-years (DALYs) lost and deaths reported in the 2010 Global Burden of Disease study. We used the comparative risk assessment method, which evaluates changes in population health that result from modifying a population's exposure to a risk factor. Population exposure was extrapolated from country-specific prevalence of smokeless tobacco consumption, and changes in population health were estimated using disease-specific risk estimates (relative risks/odds ratios) associated with it. Country-specific prevalence estimates were obtained through systematically searching for all relevant studies. Disease-specific risks were estimated by conducting systematic reviews and meta-analyses based on epidemiological studies. RESULTS: We found adult smokeless tobacco consumption figures for 115 countries and estimated burden of disease figures for 113 of these countries. Our estimates indicate that in 2010, smokeless tobacco use led to 1.7 million DALYs lost and 62,283 deaths due to cancers of mouth, pharynx and oesophagus and, based on data from the benchmark 52 country INTERHEART study, 4.7 million DALYs lost and 204,309 deaths from ischaemic heart disease. Over 85 % of this burden was in South-East Asia. CONCLUSIONS: Smokeless tobacco results in considerable, potentially preventable, global morbidity and mortality from cancer; estimates in relation to ischaemic heart disease need to be interpreted with more caution, but nonetheless suggest that the likely burden of disease is also substantial. The World Health Organization needs to consider incorporating regulation of smokeless tobacco into its Framework Convention for Tobacco Control