Current topics in the epidemiology of oral cavity and oropharyngeal cancers

Oral cancer incidence rates rose dramatically during the twentieth century in the United States and Europe, especially among individuals under the age of 60 years. Although influenced by age, sex, and country of origin, incidence trends were most strongly affected by elevated risk among individuals born after approximately 1915. This cohort effect was indicative of strong behavioral influences on oral cancer risk. In this article, associations between oral cancer risk and established behavioral risk factors including alcohol and tobacco use are reviewed. Additionally, possible associations between oral cancer risk and oral hygiene, diet, nutritional status, and sexual behavior as well as the influence of genetic factors on oral cancer risk are considered. Special emphasis is placed on evaluating possible risk differences in individuals above and below the age of 45 and in users and nonusers of alcohol and tobacco.     

Pattern of nonspecific (or global) DNA methylation in oral carcinogenesis

BACKGROUND: Although alterations in nonspecific (or global) DNA methylation (GDM) in specific cells are known to be involved in the process of lung carcinogenesis, similar associations have not been evaluated in other smoking-related cancers of the head and neck. METHODS: We evaluated the status of GDM by using monoclonal antibodies specific for 5-methylcytosine (5-mc) in oral squamous cell carcinoma (SCC) specimens of 48 cigarette smokers who had SCC develop and in 93 age-, race-, and sex-matched smokers who did not. RESULTS: Percentages of cells positive for 5-mc immunostaining of DNA of SCC and dysplastic lesions were significantly higher than those of normal oral epithelial cells from cancer subjects and from noncancer subjects. The degree of DNA methylation was unrelated to DNA content. CONCLUSIONS: The pattern of GDM in oral SCCs is different from that of lung SCCs. The differences in nutrient risk factor profiles that are related to GDM and differential activity of DNA methyltranferases between oral and lung SCCs may explain these observations.     

Utility of toluidine blue in oral premalignant lesions and squamous cell carcinoma: continuing research and implications for clinical practice

Toluidine blue (TB) has been shown to aid in the detection and diagnosis of oropharyngeal squamous cell carcinoma (OSCC) and oral premalignant lesions (OPLs). TB has been shown to enhance visualization of oral lesions and assist in identifying sites of increased risk of dysplastic/malignant change and promote biopsy. TB has been shown to identify lesions with molecular changes associated with risk of progression of OPLs to OSCC. A recent prospective longitudinal study showed TB retention in histologic benign lesions and lesions with mild dysplasia that are at increased risk of progression to cancer. Clinical trials show that TB is useful in identifying asymptomatic OSCC and premalignant lesions at risk of progressing to SCC, which might otherwise be undetected until lesions become more advanced. The data supports TB use in oral examination of patients at risk of OSCC.     

Presentation, treatment, and outcome of oral cavity cancer: a National Cancer Data Base report

BACKGROUND: Oral cancer has been identified as a significant public health threat. Systematic evaluation of the impact of this disease on the US population is of great importance to health care providers and policy makers. METHODS: This study used the National Cancer Data Base (NCDB) to evaluate associations between demographic and disease characteristics, treatment, and survival for patients with oral cavity cancer in the United States. Of patients diagnosed between 1985 and 1996, 58,976 were extracted from the NCDB. ANOVAs were performed on selected cross-tabulations, and relative survival was used to calculate outcome. RESULTS: Median age of patients was 64.0 years. Men made up 60.2% of patients. Pathologic diagnosis was squamous cell carcinoma (SCC) in 86.3% of cases. Younger patients had a much higher frequency of non-SCC, and this was related to survival in these patients. African-Americans (independent of income), lower income patients, and patients with higher grade disease were seen more frequently with advanced-stage SCC. Five-year relative survival for SCC cases was lower for older patients, men, and African-Americans. CONCLUSIONS: This study addressed many issues related to oral cancer that have been previously discussed in the literature. The demographic, site, stage, histologic, and survival data available for this large number of cases in the NCDB allowed an accurate characterization of the contemporary status of oral cancer in the United States.     

Understanding oral cancer in the genome era

Completion of the human genome project approximately 15 years ago was followed closely by advancements in array technology. Investigators quickly applied this new powerful tool to the genomic and proteomic study of oral squamous cell carcinoma (OSCC). Resultant publications documented chromosome, gene, mRNA, and protein alterations that characterize oral cancer. In this review, we summarize how the genomic, proteomic, and epigenetic array studies have provided insight into the process of oral carcinogenesis. We discuss the significant limitations and requirement for validation of these array studies. We also review the manner in which state‐of‐the‐art, high‐throughput approaches are being used to search for salivary and serum oral cancer biomarkers. © 2010 Wiley Periodicals, Inc. Head Neck, 2010     

Hepatocellular Carcinoma Associated with Precocious Puberty and Oral Contraceptives. A Case Report

A 36-year-old woman presented with sudden abdominal pain and vomiting. Computed tomography showed a tumour of the right hepatic lobe with possible signs of acute haemorrhage. Her medical history revealed precocious puberty when she was a 5-year-old and the use of oral contraceptives for 18 years. Bisegmentectomy was performed and histological examination revealed hepatocellular carcinoma. The role of male and female sex hormones in the development of hepatic tumours has been well documented but, to our knowledge, association with precocious puberty has not yet been described.     

Application of salivary noncoding microRNAs for the diagnosis of oral cancers

Oral cancer is on the rise globally and survival rates, despite improvements in clinical care, have not significantly improved. Early detection followed by immediate intervention is key to improving patient outcomes. The use of biomarkers has changed the diagnostic landscape for many cancers. For oral cancers, visual inspection followed by a tissue biopsy is standard practice. The discovery of microRNAs as potential biomarkers has attracted clinical interest but several challenges remain. These microRNAs can be found in bodily fluids such as blood and saliva which have been investigated as potential sources of biomarker discovery. As oral cancer is localized within the oral cavity, saliva may contain clinically relevant molecular markers for disease detection. Our review provides an outline of the current advances for the application of salivary microRNAs in oral cancer. We also provide a technical guide for the processing of salivary RNAs to ensure accurate clinical measurement and validation.     

Squamous cell carcinoma of the buccal mucosa: one institution's experience with 119 previously untreated patients

BACKGROUND: Squamous cell carcinoma (SCC) of the buccal mucosa is a rare, but especially aggressive, form of oral cavity cancer, associated with a high rate of locoregional recurrence and poor survival. We reviewed our institution's experience with 119 consecutive, previously untreated patients with buccal SCC. METHODS: We reviewed the charts of 250 patients who were seen at The University of Texas M. D. Anderson Cancer Center between January, 1974, and December, 1993. Of these, 119 were untreated and were subsequently treated exclusively at our institution. Patients who were previously treated elsewhere or whose lesions arose in other sites and only secondarily involved the buccal mucosa were excluded. RESULTS: Patients with T1- or T2-sized tumors had only a 78% and 66% 5-year survival, respectively. Muscle invasion, Stensen's duct involvement, and extracapsular spread of involved lymph nodes were all associated with decreased survival (p <.05). Surgical salvage for patients with locoregional recurrence after radiation therapy was rarely successful. CONCLUSIONS: SCC of the buccal mucosa is a highly aggressive form of oral cavity cancer, with a tendency to recur locoregionally. Patients with buccal mucosa SCC have a worse stage-for-stage survival rate than do patients with other oral cavity sites.     

Detection and diagnosis of oral cancer by light-induced fluorescence

BACKGROUND AND OBJECTIVE: New techniques for non-invasive early detection and diagnosis of oral dysplasia and carcinoma are required. Our objective was to determine in the hamster cheek pouch model whether differentiation between the healthy tissue and the different stages of oral premalignancy and malignancy is possible using laser-induced fluorescence after tissue exposure to 5-Aminolevulinic acid (ALA). STUDY DESIGN/MATERIALS AND METHODS: DMBA carcinogenesis was applied to one cheek pouch in 18 hamsters for 0-20 weeks. Prior to sacrifice, 20% ALA was applied to the cheek tissues. Excised cheek tissues were cryosectioned and imaged using fluorescence microscopy with excitation at 405 nm, detection at 635 nm. After fluorescence measurement, H&E staining and histopathological evaluation were performed. RESULTS: Fluorescence intensity was significantly lower in healthy tissue than in pathological tissues. Significantly higher intensities and more "fluorescence hot spots" occurred in severe dysplasia and carcinoma than in healthy tissue, hyperkeratosis, mild and moderate dysplasia. CONCLUSIONS: Light-induced fluorescence after ALA exposure can differentiate between the different stages of premalignancy and malignancy. Its ability to differentiate between healthy tissue and early pathology is particularly interesting     

Recent advances in optical diagnosis of oral cancers: Review and future perspectives

Optical diagnosis techniques offer several advantages over traditional approaches, including objectivity, speed, and cost, and these label‐free, noninvasive methods have the potential to change the future workflow of cancer management. The oral cavity is particularly accessible and, thus, such methods may serve as alternate/adjunct tools to traditional methods. Recently, in vivo human clinical studies have been initiated with a view to clinical translation of such technologies. A comprehensive review of optical methods in oral cancer diagnosis is presented. After an introduction to the epidemiology and etiological factors associated with oral cancers currently used, diagnostic methods and their limitations are presented. A thorough review of fluorescence, infrared absorption, and Raman spectroscopic methods in oral cancer diagnosis is presented. The applicability of minimally invasive methods based on serum/saliva is also discussed. The review concludes with a discussion on future demands and scope of developments from a clinical point of view. © 2015 Wiley Periodicals, Inc. Head Neck 38 : E2403–E2411, 2016     

Longitudinal health-related quality of life after mandibular resection for oral cancer: a comparison between rim and segment

BACKGROUND: Mandibular resection for oral cancer is often necessary to achieve an adequate margin of tumor clearance. Segmental mandibulectomy has been associated with a poor health-related quality of life (HRQOL), particularly before composite free tissue transfer to reconstruct the defect. Little is published in the literature contrasting the subjective deficit of segmental compared with rim resection. The aim of this study was to use a validated head and neck HRQOL questionnaire to compare rim and segmental mandibular resection in patients having primary surgery for oral cancer. METHOD: There were 224 consecutive patients between 1995 and 1999 who were treated by primary surgery for oral squamous cell carcinoma. One hundred twenty-tree had no mandibular resection, 44 had a rim resection, and 57 had a segmental resection. The University of Washington Quality of life questionnaire (UW-QOL) was administered before treatment, at 6 months, 12 months and after 18 months. RESULTS: Preoperatively, patients undergoing segmental resection reported significantly more pain, chewing problems, and a lower composite UW-QOL score. Postoperatively, the segment group tended to score worse at all time points, particularly in appearance, swallowing, recreation, and chewing; however, the difference between rim and segment was only seen in smaller resections without adjuvant radiotherapy. Little difference was seen between rim or segment for tumors < 4 cm with radiotherapy and between rim and segments for tumors > 4 cm. CONCLUSION: After segmental mandibulectomy and reconstruction using composite free tissue transfer, the UW-QOL scores were relatively good. The only 2 difference between rim and segments was noted in the small resections without radiotherapy, and some of this was reflected in differences at baseline.     

Speech outcome after surgical treatment for oral and oropharyngeal cancer: a longitudinal assessment of patients reconstructed by a microvascular flap

BACKGROUND: The aim of the study was to analyze speech outcome for patients with advanced oral/oropharyngeal cancer treated with reconstructive surgery and adjuvant radiotherapy. METHODS: Speech tests (communicative suitability, intelligibility, articulation, nasality, and consonant errors) were performed in a control group and in patients before treatment (n = 76), and 6 months (n = 51) and 12 months (n = 42) after treatment. RESULTS: Speech tests were significantly worse for patients before and after treatment compared with the controls. Speech did not improve between 6 and 12 months. After treatment, patients with T3-4 tumors showed a significantly worse score for communicative suitability, intelligibility, and articulation than patients with T2 tumors. No significant differences were found for subsites after treatment, although patients with mobile tongue tumors showed the best results. CONCLUSION: Speech difficulties are significant, and with the knowledge of this study better counseling and vigilance as to speech difficulties may be possible in patients undergoing treatment for oral/oropharyngeal cancer.     

In vivo optical coherence tomography for the diagnosis of oral malignancy

BACKGROUND AND OBJECTIVE: Oral cancer results in 10,000 U.S. deaths annually. Improved highly sensitive diagnostics allowing early detection of oral cancer would benefit patient survival and quality of life. Objective was to investigate in vivo non-invasive optical coherence tomography (OCT) techniques for imaging and diagnosing neoplasia-related epithelial, sub-epithelial changes throughout carcinogenesis. STUDY DESIGN/MATERIALS AND METHODS: In the standard hamster cheek pouch model for oral carcinogenesis (n = 36), in vivo OCT was used to image epithelial and sub-epithelial change. OCT- and histopathology-based diagnoses on a scale of 0 (healthy) to 6 (squamous cell carcinoma, SCC) were performed at all stages throughout carcinogenesis by two blinded investigators. RESULTS: Epithelial, sub-epithelial structures were clearly discernible using OCT. OCT diagnosis agreed with the histopathological gold standard in 80% of readings. CONCLUSION: In vivo OCT demonstrates excellent potential as a diagnostic tool in the oral cavity.     

Histopathologic parameters in the evaluation of T1 squamous cell carcinomas of the oral cavity

BACKGROUND: Prognostic indicators that could assist in a more precise selection of patients with small oral carcinomas for differentiated therapy would be valuable. A significant fraction of patients with stage I disease have a relatively poor prognosis despite the small size of the tumor, but in general stage I tumors of the oral cavity have a favorable prognosis. METHODS: Seventy-eight patients with stage I (T1N0M0) oral squamous cell carcinoma from two different ENT departments were included in the study. The pretreatment biopsy specimens were graded according to the modified classification of Jakobsson et al. Eight individual parameters were recorded, four parameters describing the tumor cell population and four parameters describing the tumor/host interaction. RESULTS: The only significant prognostic parameter for disease-specific survival was "mode of invasion." The histologic mean score was not significantly correlated to disease-specific or crude survival. CONCLUSIONS: Mode of invasion is the most important histologic parameter when evaluating the prognosis. Histologic evaluation of small squamous cell carcinomas of the oral cavity may assist the design of a differentiated treatment strategy (eg, monotherapy vs combined treatment).     

Anatomically‐based transoral surgical approach to early‐stage oral tongue squamous cell carcinoma

The mainstream of treatment of early‐stage oral tongue squamous cell carcinoma (OTSCC) is represented by transoral resection with “adequate” free margins. Despite that, a precise and shared definition of “adequate margin” is lacking, and so is a standardized transoral surgical technique.The tongue is a symmetrically paired organ, consisting of intertwining intrinsic and extrinsic muscles, which can be distinguished during dissection. Routes of tumoral spread in oral tongue cancer are well‐known and should be taken into account during resection. We propose herein a standardized and replicable surgical technique to resect early‐stage OTSCC, based on rational anatomical considerations.     

Quality of life and oral function in patients treated with radiation therapy for head and neck cancer

BACKGROUND: Multiple oral complaints develop during radiation therapy for head and neck cancer, and quality of life is affected after treatment. The purpose of this investigation was to assess the quality of life, oral function, and oral symptoms in a cohort of patients during and after radiation therapy. METHODS: A general quality of life survey (the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), with an added oral symptom and function scale was administered to a consecutive series of patients who received radiation therapy for head and neck malignant disease. Patients completed surveys at the beginning of radiation therapy, immediately after, and 6 months after treatment. RESULTS AND DISCUSSION: The questionnaire used in this study provides increased information regarding the oral and dental function that is frequently affected by radiation therapy. Results of this study indicate the need to determine oral dysfunction after head and neck cancer therapy, so that the most predictable cure or best palliation of the malignancy with the least impact on oral function and quality of life is chosen. Oral complications during and after radiation therapy for head and neck cancer are common and affect quality of life. Oral QOL does not return to pretreatment levels by 6 months after radiation therapy. This study supports the use of a general function scale such as the EORTC questionnaire with the addition of disease/site-specific scales to provide data on outcomes of therapy and on the complications associated with therapy. The EORTC QLQ 30 questionnaire with the oral assessment addendum provides a measure of the quality of life and oral function in head and neck cancer patients and may provide useful outcome measures for assessment of oral care prevention and management strategies in these patient populations. The results show that the questionnaire is responsive to change throughout the course of radiation therapy for head and neck cancer.     

Expression of PCNA, p53, Bax, and Bcl-X in oral poorly differentiated and basaloid squamous cell carcinoma: relationships with prognosis

BACKGROUND: The aim of this study was to compare the clinical features and proliferating cell nuclear antigen (PCNA), p53, Bcl-X, and Bax expression in primary oral basaloid squamous cell carcinoma (BSCC) and poorly differentiated squamous cell carcinoma (PDSCC) matched by stage and site and to assess the possible prognostic significance of these variables. METHODS: Seventeen cases of oral BSCC were compared with 27 PDSCCs matched by stage and tumor site. In addition, PCNA, p53, Bax, and Bcl-X expression in both carcinomas were evaluated in relation to their clinicopathologic features and prognostic values using the Kaplan-Meier method and Cox regression models. RESULTS: No statistically significant differences were found between the groups (BSCC and PDSCC) in regard to clinical features and immunohistochemical reactivity for antibodies PCNA, p53, and Bcl-X. In comparison with PDSCC, the BSCC group exhibited a higher Bax score (p = .031). The 5-year and 10-year overall survival, cancer-specific survival, and disease-free survival rates demonstrated no significant differences between the BSCC and PDSCC groups, and the PCNA, p53, Bax, and Bcl-X also showed no prognostic value. CONCLUSIONS: These results suggest that the clinical and biologic course of BSCC is similar to PDSCC in the oral cavity when clinical stage and site are matched.     

Significance of the juxtaoral organ (of Chievitz)

BACKGROUND: Most physicians are unaware of the juxtaoral organ (of Chievitz) and its clinical significance. The aim of this review is to draw attention to the clinical importance of this organ. METHODS: Review and interpretation of the English and non-English literature pertaining to the juxtaoral organ. RESULTS: The juxtaoral organ is a small structure located within the soft tissue overlying the angle of the mandible in the buccotemporal space. It is composed of an epithelial parenchyma embedded in a highly organized connective tissue stroma rich in nerves and sensory receptors innervated by the buccal nerve. This metabolically active structure presumably serves as a mechanosensor in the lateral wall of the oral cavity. Needless surgical removal of this juxtaoral structure is therefore best avoided. In children, the normal organ may be discovered as a small mass in the cheeks, which may lead to extensive and unnecessary investigations. Hyperplasia of the parenchyma may occur, but carcinoma originating from this organ has not been reported. CONCLUSION: Awareness of this normal anatomic structure is important, because the finding of epithelial islands intimately admixed with nerves could be misinterpreted as perineural invasion by carcinoma.