Oral Oncology Research Articles

1st World Congress of the International Academy of Oral Oncology: oral cancer – a global challenge

The International Academy of Oral Oncology (IAOO) was founded in 2005 with the aim of bringing together key personnel involved in the management of oral cancer. The aim of the Academy was to ‘impro...

Meeting of oral oncology experts

Meeting of oral oncology experts

O192 Ageism in oral oncology – fact or fiction?

O192 Ageism in oral oncology – fact or fiction?

P65 Advantages of using harmonic scalpel in oral oncology and its sequelae

P65 Advantages of using harmonic scalpel in oral oncology and its sequelae

Human papillomavirus: Its identikit and controversial role in oral oncogenesis, premalignant and malignant lesions (Review)

Human papillomaviruses (HPVs) are a group of host-specific DNA viruses, with a remarkable epithelial cell specificity: they have been reported principally in the ano-genital tract, urethra, skin, larynx, tracheo-bronchial and oral mucosa. More than 100 different HPV types have been identified and classified as high (e.g. 16, 18, 31) or low (e.g. 11, 42, 36) -risk (HR and LR), based on their association with cervical carcinoma. The carcinogenic role of HR-HPV revolves mainly around two of its oncoproteins: HPV-E6 which promotes degradation of the p53 tumour suppressor gene product and HPV-E7 which modifies the pRb tumour suppressor gene product, inhibiting the activity of TGF-beta2. Since these viral oncoproteins are capable of transforming primary human keratinocytes from either genital or upper respiratory tract epithelia, they have been considered to play a role in disrupting cell-cycle regulatory pathways leading to a genetic progression to ano-genital cancer and, possibly, also to oral squamous cell carcinoma (OSCC). Recently, the oncogene HPV-E5 has also been found to transform cells by modulating growth factor receptors. On the basis of the high, although very variable, frequency of HR-HPV in OSCC, an oral malignant potential of HPV infection has been hypothesised but not definitively confirmed. Major aims of this review are to update the understanding of HPV activities with respect to oral oncology and to comment on the HPV DNA reported frequencies in OSCC and potentially malignant oral lesions. A computer database search was performed, through the use of MEDLINE (PubMED) and Cochrane Library, for the last three decades. Search key words used were: human papillomavirus, HPV and cancer, HPV and oral lesions, HPV and oral premalignant lesions, HPV and oral cancer, HPV and HNSCC, HPV and oral mucosa. The search was of all fields, all languages and all dates available.

Avaliação de dois métodos de extração de DNA de material parafinado para amplificação em PCR

BACKGROUND: There are several methods for DNA extraction from formalin-fixed paraffin-embedded tissues reported in the literature. High success rate on this procedure is important for the use of molecular diagnostic methods based on the polymerase chain reaction (PCR). OBJECTIVE: Two methods of DNA extraction from paraffin-embedded samples were tested aiming at PCR amplification of genomic DNA. MATERIAL AND METHOD: Thirty-five samples were obtained from patients with squamous cell carcinoma of mouth floor treated at the Oral Oncology Center in Universidade Estadual Paulista. The DNA extraction methods included: 1. proteinase K digestion followed by Chelex 100® (BioRad) purification and 2. QIAamp DNA minikit® system (Qiagen). Purified DNA was quantified by spectrophometry and a beta-globin gene fragment was amplified using PCR. RESULTS: The DNA concentration from samples applied to the first method presented an average of 120.62 ng/µl and absorbance ratio 260/280 varying between 0.8 and 1.41. From the samples extracted using the second procedure, the mean DNA concentration was 67.38 ng/µl, with absorbance ratio varying between 1.11 and 2.53. DNA samples were submitted to PCR and from 35 samples extracted with both methods, respectively, 29 and 30 were successfully amplified for the beta-globin gene. CONCLUSION: Both methods used to obtain genomic DNA from formalin-fixed paraffin-embedded tissues presented similar performance, revealing their potential to be included in diagnosis of molecular biology, as well as in retrospective studies using archived paraffin-embedded samples.

P16 INK4A in Oral Squamous Cell Carcinomas—A Correlation With Biological Behaviors: Immunohistochemical and FISH Analysis

The p16(INK4A) gene and Rb gene are key tumor suppressor genes in a cell cycle regulatory pathway that is commonly inactivated in various cancers. The disruption of p16(INK4A) expression has been reported in several types of carcinoma but sparse in the area of oral oncology. The study included 66 cases who were diagnosed as oral squamous cell carcinoma. Immunohistochemical p16(INK4A) and pRb expression, fluorescence in situ hybridization analysis were performed to the resected materials. p16(INK4A) protein expressions were detected in 14 cases without lymph node metastasis versus in 4 cases with metastasis (P = .04). As to histopathological grading of the effect of chemotherapy, almost all the p16(INK4A)-positive cases (9 cases out of 10) exhibited the histological feature of being rather sensitive to chemotherapy (2B and better response according to Ohboshi and Shimosato's criteria) versus 17 of 33 negative cases (P = .02). Survival curves showed that the survival rate of patients with loss of p16(INK4A) expression was significantly worse than those with amplification and normal genetic dosage of p16(INK4A) (P < .0001). The expressions of p16(INK4A) were significantly correlated with biological behavior of OSCCs. These results indicate we can use p16(INK4A) as a marker of a prognostic prediction of oral cancer and it is useful for management of OSCCs.

Antimicrobials, mucosal coating agents, anesthetics, analgesics, and nutritional supplements for alimentary tract mucositis

This review focuses on the value of several groups of agents for the prevention and treatment of mucositis. The review refers to alimentary mucositis as a generalized term that includes oral mucositis and gastrointestinal mucositis. This paper is part of the systematic review made by the mucositis study group which operates in the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO). Several new guidelines are suggested in this review as an update to the primary systematic review that was published by the same group in 2004.

Promulgation of guidelines for mucositis management: educating health care professionals and patients

The Multinational Association for Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) Mucositis and Patient and Professional Education Study Groups are collaborating to improve the promulgation of the updated mucositis management guidelines. The initial step in the collaboration was to survey cancer care health professionals to determine their awareness of the original 2004 guidelines and their opinions on the usefulness of patient educational materials based on the guidelines. The authors surveyed four samples (three US and one European) of cancer health care professionals attending three cancer-related professional conferences between May and July 2005 using a ten-item questionnaire in both paper-and-pencil and web-based formats. Data were compiled and analyzed using descriptive statistics. All respondents were generally aware of the importance of mucositis as a treatment-limiting toxicity with life-threatening complications and endorsed regular oral assessment and dental care practices. Only about one third of the US respondents were aware of the 2004 guidelines in contrast to 80% of the European respondents. A majority of respondents across all four surveys (66-93%) felt strongly that educational materials based on the guidelines were needed and that they would use them, while a smaller number (7-29%) indicated they might use them if a patient had a problem with mucositis. Awareness of the guidelines remains limited in the US, and use of the guidelines worldwide is minimal. The Mucositis and Patient and Professional Education Study Groups have developed a set of strategies to enhance dissemination, awareness, and use of the updated guidelines and to promote patient education based on the guidelines. Future work will focus on implementation and evaluation of the guidelines in clinical practice.

The role of basic oral care and good clinical practice principles in the management of oral mucositis

The Basic Oral Care Group is one of eight subcommittees functioning within the Mucositis Study Group Guidelines Panel of the Multinational Association of Supportive Care in Cancer and International Society for Oral Oncology (MASCC/ISOO). The Basic Oral Care Group, comprised of the four authors of this paper, represented the disciplines of nursing (DBM, JJ), dentistry (MEPC), and pediatric dentistry (PW). This group reviewed research and clinical literature to update the original 2004 Mucositis Management Guidelines in the areas of basic oral care, bland rinses, protocols and education, and good clinical practices such as pain management, oral assessment, oral care, and dental care. Over 100 articles published between 2000 and 2005 were identified, and 32 of these were useful for the analysis. Each article was rated by at least two authors using a structured rating form and systematic determination of levels of evidence, based on the American Society of Clinical Oncology criteria. Discussion at the 2005 MASCC/ISOO Geneva pre-conference meeting of the Guidelines Panel resulted in the development of consensus on the interpretation of the literature. Based on the literature and on Panel discussions, a revision of the original guidelines for protocols and education was produced by the group, and they developed a set of recommendations related to good clinical practices. Although research remains scanty for components of basic oral care, bland rinses, protocols, and education, the original 2004 guidelines with the help of newer literature from 2000 to 2005 and expert consensus among the Guidelines Panel enabled the development of useful clinical practice guidelines for managing oral mucositis in patients receiving cancer treatment with radiation and/or chemotherapy.

Growth factors and cytokines in the prevention and treatment of oral and gastrointestinal mucositis

Growth factors and cytokines may be useful in preventing chemotherapy (CT)- and radiotherapy (RT)-induced oral and gastrointestinal mucositis. Two systematic reviews of the medical literature on growth factors and cytokines for the amelioration of CT- and RT-induced mucositis throughout the alimentary tract were performed by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology. The aim of these evidence-based scientific reviews was to critically evaluate the literature and create evidence-based guidelines for the use of growth factors and cytokines in the prevention or treatment of CT- and RT-induced mucositis. The two reviews covered articles on clinical trials from January 1966 through May 2002 and preclinical studies from June 2002 through May 2005, respectively. The systematic review process was based on a well-established method for evaluating scientific literature. The number of articles in the first review was 29. In the second review, 23 articles were evaluated, 14 preclinical and 9 clinical studies. It was concluded from the first review that there was no sufficient evidence to provide any recommendations for clinical practice guidelines regarding growth factors and cytokines. From the second review, a guideline could be presented recommending the use of recombinant human keratinocyte growth factor-1 (palifermin) to prevent oral mucositis in patients receiving high-dose CT and total body irradiation followed by stem cell transplantation for haematological malignancies. A guideline could also be provided suggesting that granulocyte macrophage colony-stimulating factor mouthwash not be used for the prevention of oral mucositis in the transplant setting with high-dose CT and autologous or allogeneic stem cell transplantation. These systematic reviews have provided clarity and shown exciting new results. Further studies will provide new options for this debilitating side-effect of cancer therapy.

Alimentary mucositis: putting the guidelines into practice

The Mucositis Study Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology completed an evidence-based review of the literature for the management of alimentary mucositis. The present manuscript puts these guidelines into clinical practice by presenting two cases of alimentary mucositis from cancer therapy. These cases illustrate the impact of oral and gastrointestinal mucositis on patient care.

Developing evidence-based guidelines for management of alimentary mucositis: process and pitfalls

It is important yet difficult to maintain currency in clinical oncology practice. The emergence of new diagnostic technologies and new paradigms for cancer treatment combine to produce a rapidly changing clinical approach to patients aided by the increasing use of multidisciplinary care teams and development of evidence-based protocols. Teams of experts review the literature in a given area and produce management guidelines and protocols for use by practicing clinicians. Traditionally within Hematology/Oncology, these guidelines have been directed to management of a given tumor type. However, in recent years, attention has increasingly turned to supportive oncology; for example, there are now management guidelines for conditions such as neutropenic fever [Hughes et al. Clinical Infectious Diseases 34(6):730-751, 2002], antiemetic (The Antiemetic Subcommittee of the Multinational Association of Supportive Care in Cancer Annals of Oncology 17:20-28, 2006) and most recently, mucositis [Rubenstein et al. Cancer 100(9 Suppl):2026-2046, 2004]. It is critical that any guideline process should include education, evaluation, and timely update in its remit, because guidelines become highly compromised if their existence is not widely known, if they do not facilitate clinical practice, or if they are not reflective of contemporary medical literature. The Mucositis Study Group (MSG) of the Multinational Association for Supportive Care in Cancer/International Society for Oral Oncology was created in 1998 to specifically address the multiprofessional approach to clinical care, research, and education associated with mucosal injury in cancer patients. A specific outcome has been the development of evidence-based guidelines for the management of mucositis [Rubenstein et al. Cancer 100(9 Suppl):2026-2046, 2004; The Mucositis Study Group of MASCC/ISSO 2005]. The original guidelines [Rubenstein et al. Cancer 100(9 Suppl):2026-2046, 2004] and a companion paper discussing the science behind mucositis [Sonis et al. Cancer 100(9):1995-2025, 2004], were published in 2004. The MSG has recently updated the guidelines [The Mucositis Study Group of MASCC/ISSO 2005]. This paper discusses the process involved and the lessons learned that might help other groups planning to undertake a similar project.

Amifostine in the management of radiation-induced and chemo-induced mucositis

Mucositis is a significant complication of cancer therapy, with important clinical and economic implications. In June 2005, the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) conducted an evidence-based update review of the literature on mucositis. The goal of this literature review is to update previously published guidelines for the management of mucositis. This article reports the findings of the subgroup charged with reviewing the literature related to amifostine.

The role of alternative and natural agents, cryotherapy, and/or laser for management of alimentary mucositis

To review the literature and update the current guidelines of alternative/natural agents, cryotherapy, and/or laser therapy in the management of alimentary mucositis (AM). The original guidelines developed by the Multinational Association for Supportive Care in Cancer (MASCC)/International Society for Oral Oncology (ISOO) mucositis study group were the basis for this study. A medical librarian conducted an initial Medline search to identify research articles published between 2002 and 2005 in English language. A search term combination that included stomatitis, mucositis, mucous membrane, neoplasm, lasers, complimentary therapies, amino acids, antioxidants, vitamins, minerals, plant extracts, and cryotherapy was conducted. This initial search identified articles with a strong scientific methodology that included both preclinical and clinical research. Using standardized scoring forms, authors reviewed and scored individual articles. A consensus result of the review was achieved in a meeting of reviewers in June of 2005. The initial search identified a total of 167 new articles. Of these, 14 were selected and reviewed: alternative/natural therapy (one preclinical study); cryotherapy (four clinical studies); lasers (two clinical studies); and alternative/natural agents (seven clinical studies). A new guideline could be established for the use of cryotherapy in the management of AM in hematopoietic stem cell transplant (HSCT) patients receiving melphalan in the conditioning phase. The rapid progress in the understanding of AM created a need for new prevention and management protocols. Frequent literature review is now necessary to identify agents and protocols being developed in this important area of supportive care in cancer.

Anti-inflammatory agents in the management of alimentary mucositis

Alimentary mucositis is a significant complication of cancer therapy, with important clinical and economic implications. In June 2005, the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology conducted an evidence-based review of the literature on alimentary mucositis. The goal of this literature review was to update previously published guidelines for the management of mucositis. This article reports the findings of the subgroup charged with reviewing the literature related to anti-inflammatory interventions. Considerable preclinical and clinical evidence suggests that the use of anti-inflammatory agents may be a promising approach to reduce the severity of mucositis. However, there was not enough evidence to support any new guidelines advocating the use of any specific anti-inflammatory intervention. Thus, there is a need for well-designed clinical trials evaluating the use of anti-inflammatory agents in the management of mucositis.

Risk factors of laryngeal cancer in patients attended in the oral oncology center of Araçatuba

The laryngeal cancer is the second most common respiratory cancer worldwide. The aim of this study is to perform a survey on data related to the incidence of laryngeal cancer that would enable its analysis among patients with larynx cancer attended at the Oral Oncology Center from the Dentistry School - UNESP, Aracatuba-SP-BR. Out of the 66 cases of cancer registered at the Oncologic Treatment Center between 1991 and 2003, 64 cases were identified in men. Information of gender, age, race, tobacco and alcohol use and occupational history were obtained from patients through a standardized questionnaire. The largest number of cases of laryngeal cancer occurred among farmers, building constructions workers and drivers. The incidence was higher among smokers, white individuals with ages ranging from 50 to 60 years. In conclusion, the risk of laryngeal cancer was associated to several factors, also occurring due to the effect of the socio-economic status, diet, income and educational level.

RETRACTED: Overexpression of cyclooxygenase-2 in nasopharyngeal carcinoma and association with lymph node metastasis

This article has ben retracted by the authors and editors. Please see http://www.elsevier.com/wps/locate/withdrawalpolicy.Reason: Readers are asked to note that the named authors and editors of this paper published in Oral Oncology have requested that it should be retracted due to concerns relating to some of the specific patient’s information. It is understood by the Publisher that some of the patient’s information has not been correctly registered and therefore, this may have affected the authors’ conclusion in this paper.Oral Oncology and the publishers, Elsevier, are keen to ensure that papers published in this journal maintain high levels of clinical accuracy and academic excellence in all papers accepted for publication.

Engineering craniofacial scaffolds

To develop an integrated approach for engineering craniofacial scaffolds and to demonstrate that these engineered scaffolds would have mechanical properties in the range of craniofacial tissue and support bone regeneration for craniofacial reconstruction. Scaffold architecture designed to achieve desired elasticity and permeability. Scaffold external shape designed to match craniofacial anatomy. Final fabricated biomaterial scaffolds. Compressive mechanical modulus and strength. Bone regeneration as measured by micro-CT scanning, mechanical testing and histology. Departments of Biomedical Engineering, Oral/Maxillofacial Surgery, and Oral Medicine, Pathology and Oncology at the University of Michigan. Results showed that the design/fabrication approach could create scaffolds with designed porous architecture to match craniofacial anatomy. These scaffolds could be fabricated from a wide range of biomaterials, including titanium, degradable polymers, and degradable calcium phosphate ceramics. Mechanical tests showed that fabricated scaffolds had compressive modulus ranging 50 to 2900 MPa and compressive strength ranging from 2 to over 56 MPa, within the range of human craniofacial trabecular bone. In vivo testing of designed scaffolds showed that they could support bone regeneration via delivery of BMP-7 transduced human gingival fibroblasts in a mouse model. Designed hydroxyapatite scaffolds with pore diameters ranging from 400 to 1200 microns were implanted in minipig mandibular defects for 6 and 18 weeks. Results showed substantial bone ingrowth (between 40 and 50% at 6 weeks, between 70 and 80% at 18 weeks) for all scaffolds, with no significant difference based on pore diameter. Integrated image-based design and solid free-form fabrication can create scaffolds that attain desired elasticity and permeability while fitting any 3D craniofacial defect. The scaffolds could be manufactured from degradable polymers, calcium phosphate ceramics and titanium. The designed scaffolds supported significant bone regeneration for all pore sizes ranging from 300 to 1200 microns. These results suggest that designed scaffolds are clinically applicable for complex craniofacial reconstruction.

Although leukoplakia responds to some treatments relapses and adverse effects are common

The Cochrane Oral Health Group's Trials Register, Cochrane Central Trials Register, Medline and Embase were searched, as well as the following journals: Cancer, Community Dentistry and Oral Epidemiology, European Journal of Oral Sciences, Journal of Dental Research, Oral Oncology, Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics. The reference lists of included studies and reviews were checked, and oral medicine experts were contacted through a European mailing list (EURORALMED). Randomised controlled trials (RCT) were included if they had enrolled patients who had a diagnosis of oral leukoplakia and who were undergoing any surgical or medical (topical and systemic) treatment. The primary outcome considered was malignant transformation of leukoplakia demonstrated by histopathological examination. Other outcomes considered were clinical resolution, histological modification and frequency of adverse effects. Data were collected using a specific extraction form. The validity of studies included was assessed by two reviewers, on the basis of the method of allocation concealment, blindness of the study and loss of participants. Data were analysed by calculating relative risk (RR). When valid and relevant data were collected, a meta-analysis of the data was undertaken. The possible effectiveness of surgical interventions, including laser therapy and cryotherapy, has never been studied by means of an RCT. Nineteen RCT of nonsurgical interventions were identified: seven were included. Vitamin A and retinoids were tested in five RCT (245 patients); the other drugs tested were bleomycin (one study), mixed tea (one study) and beta-carotene (one study). Malignant transformation was recorded in just two studies. None of the treatments tested showed a benefit compared with placebo. Treatment with beta-carotene and vitamin A or retinoids was associated with significant rates of clinical resolution, compared with placebo or absence of treatment. Whenever reported, a high rate of relapse was a common finding. Side effects of variable severity were often described but interventions were well accepted by patients, since dropout rates were similar between treatment and control. To date there is no evidence of effective treatment in preventing malignant transformation of leukoplakia. Treatments may be effective in the resolution of lesions, but relapses and adverse effects are common.