Oral cancer awareness for the general practitioner: new approaches to patient care

In Australia, oral cancer accounts for approximately 2-3 per cent of all cancers, and approximately 1 per cent of deaths from cancer. The incidence of intra-oral cancer is gradually increasing. It is now well established that early detection of potentially malignant disease can improve the clinical outcome for patients, and as such it is the responsibility of dentists to identify such lesions early. To facilitate early detection of suspicious oral lesions several clinical methods of detection can be used. In addition to conventional visual screening of oral tissues with the naked eye under projected incandescent or halogen illumination, there are many clinical diagnostic aids that can be undertaken to help detect oral cancer. In this article we explore clinically available modalities that may be used by the general dental practitioner, and highlight their inherent strengths and weaknesses.     

Diagnostic aids in detection of oral cancer: An update

Oral cancer is the sixth most common malignancy with almost 500000 new cases reported worldwide annually. The diagnosis of oral cancer at an early stage has a good prognosis as the survival rate is high (around 80%). However, the majority of oral cancer cases are diagnosed at a later stage with a considerably poor 5-year survival rate of 50% according to World Health Organization statistics. Thus, an effective management strategy for oral cancer will depend on its early identification and intervention which would pave the way for superior prognosis. Despite the obvious advantage of earlier diagnosis of oral cancer, no approach has yet proven to be a reliably successful in diagnosis of oral cancer at an early stage. Currently; the primary line of screening of oral cancer is performed by visual inspection, which is a subjective examination. Among the screening tests or diagnostic aids now available for oral cancer, few (toluidine blue, brush biopsy, salivary and serum bio-markers) have been utilised and studied for many years while others have recently become commercially available. The authors in the present article review all the modalities of screening aids used in oral cancer detection and provide an update on the latest screening tools used in oral cancer detection.     

Squamous cell carcinoma of the oral tissues: a comprehensive review for oral healthcare providers

North Americans in 2004 were projected to die from oral and pharyngeal cancer at a rate of 1.2 per hour. Oral healthcare providers can be instrumental in reducing the incidence of oral and pharyngeal premalignant and malignant lesions by identifying patients with high-risk behavior, educating their patients about the consequences of their high-risk behavior, and by early detection of premalignant and malignant conditions. The fact only 34% of the cancers of the oral cavity and larynx are localized at the time of diagnosis and evidence that at least one third of the patients diagnosed with an oral or pharyngeal malignancy have undergone oral cancer screening within the past three years suggests the current protocol for the early detection of pre-malignant or malignant changes appears to be deficient. To facilitate early diagnosis, oral healthcare providers must take into consideration the capriciousness of oral cancer and must be familiar with the availability and application of diagnostic modalities beyond conventional visual inspection and palpation of oral soft tissues. This article provides a comprehensive review of the disease for healthcare professionals.     

Patients’ views on a proposed oral cancer screening technology

Brush cytology and telemedicine platforms are used with proven benefits in remote diagnosis of malignancies like cervical cancer. In low-resource settings access to the current standard of care, biopsy and histopathology grading of oral lesions, can be unfeasible. Risk-stratifying early malignant and oral potentially-malignant lesions can help instigate therapeutic treatment and improve prognosis. Therefore, a telecytology platform enabling remote connectivity to specialist centres may aid early detection of oral cancer. We outline head and neck (H&N) cancer patients’ views on an oral brush cytology investigation.     

Screening for oral cancer: contributing to the debate

Screening, or “case detection”, is controversial and central to much debate in the world of medicine. In the present study, we evaluate oral cancer screening against the National (UK) Screening Committee criteria in the context of the most recent research in this field. Oral cancer is a complex, debilitating disease that is increasing in incidence in the UK and in most parts of Western Europe. It has multifactorial etiology, and these major risk factors are well researched, allowing definition of an “at‐risk” population. However, our understanding of its natural history of progression from potentially malignant disorders to malignancy is limited; the field lacks high‐quality, randomized, controlled trials, bar one published study. Evidence is also available to suggest that visual screening by sufficiently trained examiners results in earlier detection (down staging) of the disease, which lends itself towards more successful treatment. Sensitive screening tools to aid and confirm findings following a visual inspection are yet to be developed. Nevertheless, new tests continue to arise based on knowledge gleaned from research into the biomarkers. This review discusses the evidence based around the oral cancer screening debate and highlights areas in which more research is required before the advent of a successful and effective screening program.     

Recent trends of saliva omics biomarkers for the diagnosis and treatment of oral cancer

BackgroundRecent advances in surgery, radiotherapy, and chemotherapy have no significant effect on oral cancer survival rates due to late diagnosis, poor tumor response to chemotherapy and radiotherapy, as well as a lack of effective biomarkers for early diagnosis.HighlightsTherefore, an investigative study aimed at identifying genomics, proteomics, metagenomics, and, metabolomics derived biomarkers for early diagnosis may improve the survival rate of oral cancer patients. Identification and application of saliva-based ‘‘omics’’ biomarkers may overcome painful invasive procedures currently being used for the diagnosis of oral cancer. One single biomarker may not be able to differentiate between oral squamous cell carcinoma (OSCC) and controls. Thus, multiple sensitive and specific biomarkers may be needed for screening high-risk patients and following them up for early signs of OSCC occurrence. Validation of these biomarkers in large patient cohorts is, however, required before they can be used in clinical practice.ConclusionIn this review, we summarize the potential of omics derived salivary biomarkers as diagnostic and prognostic tools in oral cancer detection and the future clinical benefits associated with these markers.     

Oral cancer and oral erythroplakia: an update and implication for clinicians

Despite recent advances in therapy and treatment for oral cancer, survival rates are still low. It is generally accepted that oral cancer may arise from potentially premalignant disorders. Oral erythroplakia has been identified as the one with the highest malignant transformation rates. The aim of this review was to provide detailed information on oral cancer and oral erythroplakia. Few data are available on oral erythroplakia and there is an urgent need for randomized controlled trials. Early detection and diagnosis is still the key to survival rates. Dentists and physicians may play an important role in the detection of premalignant lesions and therefore improve patients' outcome.     

Update review on prevention and early diagnosis in oral cancer

Oral cancer is a major health problem in some parts of the world, especially in developing countries. Worldwide, the annual incidence exceeds 3,000,000 new cases. The main risk factors are tobacco and alcohol. However, dietary factors, viruses and possibly genetic predisposition have also been associated with oral cancer. Several oral lesions such as leukoplakia, erythroplakia and lichen planus carry an increased risk for malignant transformation in the oral cavity. Prognosis of oral cancer differs significantly between specific oral locations, with cancer of the lip for example having a much better prognosis than at the base of tongue or on the gingiva. Prognosis of intra-oral cancer is generally poor, with a five-year survival less than 50 percent. Local recurrences as well as lymph node metastases occur in a significant percentage of patients, while distant metastases are less frequent. Prognosis correlates mainly with the size of the lesion and the nodal status at the time of diagnosis, therefore early detection of small, stage-1 oral cancer can reduce mortality and morbidity. Oral lesions can be easily observed by direct visualization, however, knowledge of the differential diagnosis of oral lesions is mandatory for early diagnosis of malignant and pre-malignant lesions in the oral cavity. Use of screening and detection aids such as vital stains and Oral CDX can increase the number of cases diagnosed at an early stage, or even in the pre-malignant stage. Development of molecular markers can improve the early diagnosis and can help in predicting treatment response. New treatment modalities including tumor specific antibodies and gene therapy are emerging, giving more hope for patients with oral cancer. There is an important role for the dentist in both early diagnosis of pre-malignant and malignant lesions, and in prevention by educating the patients of the risks associated with tobacco, alcohol and dietary factors.     

A reason for the use of toluidine blue staining in the presurgical management of patients with oral squamous cell carcinomas

Verification of oral cancer relies on histopathological diagnosis of suspect or malignant lesions. There is evidence for further pre-surgical screening procedures to localize tumor borders and define other malignant lesions. Important methods are: visual examination, including pan-endoscopy, fluorescence imaging, and brush biopsy, as well as radiologic techniques such as conventional radiography, computed tomography, magnetic resonance imaging, scintigraphy, and ultrasonography, which may reduce the mortality rate associated with oral cancer. In addition, toluidine blue staining is a simple, inexpensive, and excellent diagnostic tool. Herein we show that the clinical use of in vivo staining is effective to define the superficial tumor borders and to detect malignant or pre-malignant cells in the surrounding area of the tumor following detection of a malignancy of the oral cavity. In our reported case, the main tumor mass was surrounded by layers of an intact mucosa, yet in a distance of more than 1 cm a group of malignant or pre-malignant cells in the surrounding area required a resection of the tumor in a size that would have been unaddressed during visual examination alone followed by clinical routine program of presurgical examinations after the detection of a malignancy of the oral cavity.     

Opinions and attitudes of the UK's GDPs and specialists in oral surgery, oral medicine and surgical dentistry on oral cancer screening

OBJECTIVE: To survey two broad areas of oral cancer awareness and management of patients at risk of oral cancer by specialists in oral surgery, oral medicine, surgical dentistry and general dental practitioners (GDPs) in the UK. The first of these included knowledge and awareness of aetiological factors, changing patterns of disease, and screening/detection programmes including their effectiveness. The second included oral cancer detection methods, advice on avoidance of high-risk activity and self-examination, and referral pattern of GDPs. DESIGN AND METHOD: A pretested, 44-item questionnaire, a covering letter, a brief outline of the research protocol and return, stamped envelope were mailed in March 2003. A sample of 200 GDPs whose names were obtained from the General Dental Council's main list and 305 dental specialist names obtained from specialist's list in surgical dentistry, oral medicine and oral surgery were selected randomly. Information on oral cancer awareness and practice, screening practice and education was obtained. RESULTS: The response rate was 66.9%. The knowledge of the dental specialists was consistent with that in reports of current aetiological studies on oral cancer. However there were gaps in the GDP's knowledge and ascertainment of oral cancer risk factors. Over 70% of the dental specialists provided counselling advice on the risks of tobacco and alcohol habits compared with 41.2% of GDPs. More GDPs (52.4%) than specialists (35.4%) believed that oral cancer screening on a national basis would be effective in decreasing the mortality of oral cancer. Over 95% of all respondents used a visual examination for oral cancer screening and 89.9% of all respondents strongly believed that visual screening is effective in the early detection of oral cancer. CONCLUSION: The results showed that GDPs had knowledge gaps in their awareness of oral cancer risk factors and the application of preventive measures. Most dental health providers in the UK perform visual screening of the oral mucosa for their patients. Opinion was equivocal as to whether a nationally based screening programme similar to cervical cancer would be effective in improving the mortality and morbidity of oral cancer.     

The role of hypoxia in oral cancer and potentially malignant disorders: a review

Oral and oropharyngeal cancer are major health problems globally with over 500 000 new cases diagnosed annually. Despite the fact that oral cancer is a preventable disease and has the potential for early detection, the overall survival rate remains at around 50%. Most oral cancer cases are preceded by a group of clinical lesions designated ‘potentially malignant disorders’. It is difficult to predict if and when these lesions may transform to malignancy, and in turn it is difficult to agree on appropriate management strategies. Understanding underlying molecular pathways would help in predicting the malignant transformation of oral potentially malignant disorders and ultimately identifying effective methods for early detection and prevention of oral cancer. Reprogramming energy metabolism is an emerging hallmark of cancer that is predominantly controlled by hypoxia‐induced genes regulating angiogenesis, tumour vascularization, invasion, drug resistance and metastasis. This review aims to highlight the role of hypoxia in oral carcinogenesis and to suggest future research implications in this arena.     

Is workplace screening for potentially malignant oral disorders feasible in India?

J Oral Pathol Med (2010) 39 : 672–676 Background: Because of delays in diagnosis, oral cancer usually presents for therapy at a late stage. Patients are unaware of having lesions as they are mostly asymptomatic and physicians generally do not examine the mouth sufficiently. People in rural areas or are underserved may not frequently visit the dentist who can easily pick up these lesions early. Screening programs are useful in that regard. Such programs in general are conducted by either inviting people to come to a screening center or by health care workers visiting the individual households. However, those who work during the day may not visit screening centers or be at home during the day of the screening by a visiting health care worker. Workplace screening overcomes these challenges. Methods: To assess the feasibility of a screening program to detect potentially pre‐malignant oral disorders in a workplace in India, clinically visible mucosal lesions were compared with the clinical photographs of the same lesions assessed by an expert. Role of smoking, alcohol, and chewing betel quid and tobacco in the etiology of those lesions were assessed. Results: Sixty‐nine percent of the eligible subjects participated in the screening (n = 1613). Prevalence of leukoplakia was 5%. Bidi (OR = 35.6), and cigarette smoking (OR = 22.8), alcohol (OR = 17.6), and tobacco and areca nut chewing (OR = 7.5), were significantly associated with leukoplakia and erythroplakia (all P < 0.05). Conclusions: Conduction of a screening program by valid visual inspection to detect potentially malignant oral disorders within a workplace is not only feasible but also effective.     

Expression of p53 mutant nuclear phosphoprotein in oral carcinoma and potentially malignant oral lesions

An immunohistochemical study of primary oral squamous cell carcinomas (n = 37) with a monoclonal antibody (PAb 1801) specific to p53 antioncogene product demonstrated nuclear overexpression of the mutant protein in 35% of cases. Those positive included carcinomas without deep invasion suggesting that p53 mutation may occur in the early stages of progression of a malignancy. This is supported by the observation that mutant protein was detectable in limited amounts in 2 cases of oral mucosal dysplasia (n = 12). None of the normal or reactive oral mucosal tissues (n = 17) were positive for p53. The presence or absence of p53 was not correlated with the site of the lesion or its degree of differentiation. Our data suggest that p53 gene mutations are commonly involved in oral cancer but are neither sufficient nor necessary for the development of malignancy. Nevertheless, as this mutation is the commonest genetic change described so far in cancers in white caucasoids, it is possible that its presence can be used as a marker of risk in a high proportion of malignant and potentially malignant oral lesions.     

大数据时代口腔癌精准诊疗的思考

现代科学技术的进步使得医学数据越来越复杂、丰富和多样,生物医学已然进入大数据时代.在大数据时代背景下,当前主流的循证医学模式可能被精准医学模式替代,肿瘤的诊疗策略也在发生重大变革.本文将评述大数据时代背景下口腔癌精准诊疗策略的进展,包括口腔癌的筛查、早期诊断、分子分型、预后判断和治疗方案的选择、转移和化疗敏感性的预测等,以期为口腔癌的精准诊疗提供新的思路.     

口腔癌的预防

口腔癌是头颈部较常见的恶性肿瘤之一,其发生与多种内、外因素有关,包括吸烟、饮酒、病毒感染、营养不良、饮食习惯和局部刺激等,其中尤以吸烟、饮酒的危险性最大。尽管采用手术、放疗、化疗、生物治疗等治疗口腔癌取得了长足进展,但口腔癌的5年生存率仍然徘徊在64%左右,晚期患者的预后更差。因此,要提高口腔癌患者的生存率和生存质量,必须坚定不移地贯彻执行＂预防为主＂的卫生工作方针,力争做到早期发现、早期诊断和早期治疗。作者就目前口腔癌三级预防的相关问题进行了讨论。     

早期口腔癌检查及诊断方法的研究进展

过去几十年,口腔癌的治疗方法取得了很大进步,但中晚期口腔癌的预后并未碍到明显改善,早期诊断、早期治疗仍然是提高治愈率的关键措施.早期确诊的主要方法是切取活检,但该方法有创,且异常增生与早期口腔癌的区分过于依赖病理医师的临床经验.为诊断口腔异常增生和早期口腔癌,迫切需要可在门诊条件下操作简便、实用且无创的诊断工具.目前发展迅速的早期口腔癌检测方法包括光学系统检查、活组织染色、唾液检测、刷取活检、DNA分析等.本文对这些方法诊断口腔鳞癌及癌前病损的价值进行回顾与评价.     

Oral cancer: current and future diagnostic techniques

Oral cancer is among the 10 most common cancers worldwide, and is especially seen in disadvantaged elderly males. Early detection and prompt treatment offer the best chance for cure. As patient awareness regarding the danger of oral cancer increases, the demand for "screening" is expected to increase. The signs and symptoms of oral cancer often resemble less serious conditions more commonly found and similarly usually presenting as a lump, red or white patch or ulcer. If any such lesion does not heal within 3 weeks, a malignancy or some other serious disorder must be excluded and a biopsy may be indicated. Dental health care workers have a duty to detect benign and potentially malignant oral lesions such as oral cancer and are generally the best trained health care professionals in this field. Prompt referral to an appropriate specialist allows for the best management but, if this is not feasible, the dental practitioner should take the biopsy which should be sent to an oral/head and neck pathologist for histological evaluation.     

The role of cyclin‐dependent kinases in oral potentially malignant disorders and oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is a major global health problem with a relatively low‐moderate 5‐year survival rate. OSCC is often preceded by lesions and conditions known as oral potentially malignant disorders (OPMDs) that have an increased risk of malignant transformation. Despite advances in diagnostic technology and cancer research, the prognosis of OSCC remains poor as it is frequently detected a late stage. Understanding the molecular pathways involved in oral carcinogenesis provides a platform to identify biomarkers that may allow the early detection of OSCC and accurate prediction of the malignant potential of OPMDs. In addition, specific molecular inhibitors can be developed to target these important pathways and allow advanced therapeutic management to improve the prognosis of this malignancy. A common feature across a number of different cancers is the dysfunction of cell cycle moderator proteins known as cyclin‐dependent kinases. This review summarises the current literature regarding the role of cyclin‐dependent kinases in oral carcinogenesis with a particular focus on cyclin‐dependent kinases 4 (CDK4) and 6 (CDK6). This is of particular relevance as CDK4 and CDK6 inhibitors have shown some promising results in other cancer types and are interesting potential treatments for OSCC.     

Spanish dental students knowledge of oral malignancy and premalignancy

Background : In view of the gradual rise in oral malignancy in Europe, there is an increased need for undergraduate dental students to have some appropriate training in the recognition of the signs and symptoms of oral premalignancy and malignancy, and be aware of the appropriate early management of patients with such oral lesions. The present study outlines the results of a pilot study to determine the knowledge and awareness of a cohort of undergraduate dental students in Spain regarding the management of oral premalignancy and malignancy. Method : In March 1997 a self-administered questionnaire (SAQ) addressing student's knowledge, opinions, and related aspects of screening and detection of oral malignancy and premalignancy, was mailed to 200 undergraduate dental students in two Spanish Universities. The present report details the responses of this cohort of undergraduates. Statistical analysis of the data was performed using the χ² test and the results were considered significant when P<0.05. Results : 37.0% of the respondents were male and 63.0% female. Almost all of the respondents (99.0%) had attended general dental congresses and 81.5% had attended specific courses on oral malignancy and premalignancy. Only 20% of undergraduate students had witnessed at least one patient with oral malignancy. Squamous cell carcinoma (SCC) was the most frequently observed (94.4%) oral tumour. 79% of the respondents had examined or witnessed at least one patient with a potentially malignant lesion. Leukoplakias were the most commonly observed (80.0%) premalignant lesions. 5th year students were more likely to have performed a biopsy than 4th year students (P<0.05), particularly male students (P<0.005). 40.0% of respondents believed that the lower lip was the most common site of an oral cancer; almost half realised that a tumour could have a speckled appearance. 79% to 82% of the respondents indicated that tobacco and alcohol were the principal causes of oral SCC, but 34.6% suggested that HIV disease was a risk factor for oral SCC. Almost all respondents routinely recorded the tobacco or alcohol consumption of patients and would offer advice to patients regarding modification of these habits. 64.0% of undergraduates suggested that clinical screening at intervals of 6 to 12 months was an effective means of diagnosing oral premalignant and malignant lesions, and almost all considered oral health promotion to be an effective means of reducing oral cancer mortality. Conclusions : Undergraduate dental students in Spain have limited clinical experience or knowledge of related aspects of oral premalignant and malignant lesions, and they may fail to recognise appropriate signs and symptoms and aetiological factors of such disease.