Is the early identification and referral of suspected head and neck cancers by community pharmacists feasible? A qualitative interview study exploring the views of patients in North East England.

INTRODUCTION: Head and neck cancer (HNC) is the eighth most common cancer in the United Kingdom. Survival rates improve when the cancer is diagnosed at an early stage, highlighting a key need to identify at-risk patients. This study aimed to explore opportunistic HNC identification and referral by community pharmacists (CPs) using a symptom-based risk assessment calculator, from the perspective of patients with a diagnosis of HNC. METHODS: Purposive sampling was used to recruit patients from the HNC pathway in three large teaching hospitals in Northern England. Qualitative methodology was used to collect data through an iterative series of semistructured telephone interviews. Framework analysis was utilised to identify key themes. RESULTS: Four main themes were constructed through the analytic process: (1) HNC presentation and seeking help; (2) the role of the CP; (3) public perception of HNC and (4) the role of a symptom-based risk calculator. Participants agreed that CPs could play a role in the identification and referral of suspected HNCs, but there were concerns about access as patients frequently only encounter the medicine counter assistant when they visit the pharmacy. HNC symptoms are frequently attributed to common or minor conditions initially and therefore considered not urgent, leading to delays in seeking help. While there is public promotion for some cancers, there is little known about HNC. Early presentation of HNC can be quite variable, therefore raising awareness would help. The use of a symptom-based risk calculator was considered beneficial if it enabled earlier referral and diagnosis. Participants suggested that it would also be useful if the public were made aware of it and could self-assess their symptoms. CONCLUSION: In principle, CPs could play a role in the identification and referral of HNC, but there was uncertainty as to how the intervention would work. Future research is needed to develop an intervention that would facilitate earlier identification and referral of HNC while not disrupting CP work and that would promote HNC and the risk calculator more widely. PATIENT OR PUBLIC CONTRIBUTION: Patient and public involvement and engagement (PPIE) was integrated throughout the project. Initially, the proposal was discussed during a Cancer Head and Neck Group Experience (CHANGE) PPIE meeting. CHANGE was set up to support HNC research in 2018. The group is composed of seven members (four female, three male) with an age range of 50-71 years, who were diagnosed at Sunderland Royal Hospital. A patient representative from the University of Sunderland PPIE group and a trustee of the Northern HNC Charity were recruited as co-applicants. They attended project management group meetings and reviewed patient-facing documentation.

Expression of Epsin3 and its interaction with Notch signalling in oral epithelial dysplasia and oral squamous cell carcinoma.

BACKGROUND: Most oral squamous cell carcinoma patients present with late-stage disease. Early detection of the disease is considered to be the most effective way of improving patient outcomes. Several biomarkers have been identified as indicators of oral cancer development and progression; however, none have been translated into clinical practice. In this study, we have investigated the role of Epsin3, an endocytic adaptor protein, and Notch1, a transmembrane signalling protein, in oral carcinogenesis with a view to explore their potential as biomarkers. METHODS: Oral cancer cell lines and a normal oral keratinocyte cell line were used together with tissue samples of normal oral mucosa (n = 21), oral epithelial dysplasia (n = 74) and early stage (Stages I and II) oral squamous cell carcinoma (n = 31). Immunocytochemical staining, immunoblotting and real-time quantitative polymerase chain reaction (PCR) were performed to assess protein as well as gene expression levels. RESULTS: The expression levels of Epsin3 and Notch1 mRNA and protein are variable across different oral squamous cell carcinoma derived cell lines. Epsin3 was upregulated in oral epithelial dysplasia and oral squamous cell carcinoma tissues compared with normal epithelium. Overexpression of Epsin3 resulted in a significant reduction of Notch1 expression in oral squamous cell carcinoma. Notch1 was generally downregulated in the dysplasia and oral squamous cell carcinoma samples. CONCLUSION: Epsin3 is upregulated in oral epithelial dysplasia and oral squamous cell carcinoma and has the potential to be used as a biomarker for oral epithelial dysplasia. Notch signalling is downregulated in oral squamous cell carcinoma, possibly through an Epsin3-induced de-activation pathway.

Qualitative interview study exploring the early identification and referral of patients with suspected head and neck cancer by community pharmacists in England.

OBJECTIVE: To explore pharmacists' perceptions of, and attitudes towards, the early identification and referral of patients with signs and symptoms indicating potential diagnosis of head and neck cancer (HNC) in community pharmacy settings. DESIGN: Qualitative methodology, using constant comparative analysis to undertake an iterative series of semistructured interviews. Framework analysis facilitated the identification of salient themes. SETTING: Community pharmacies in Northern England. PARTICIPANTS: 17 community pharmacists. RESULTS: Four salient and inter-related categories emerged: (1) Opportunity and access, indicating frequent consultations with patients presenting with potential HNC symptoms and the accessible nature of community pharmacists; (2) Knowledge gap, indicating knowledge of key referral criteria, but limited experience and expertise in undertaking more holistic patient assessments to inform clinical decision making; (3) Referral pathways and workloads; indicating good working relationships with general medical practices, but limited collaboration with dental services, and a desire to engage with formal referral pathways, but current practices based entirely on signposting resulting in a potential lack of safety-netting, no auditable trail, feedback mechanism or integration into the multidisciplinary team; (4) Utilisation of clinical decision support tools; indicating that no participants were aware the Head and Neck Cancer Risk Calculator (HaNC-RC V2) for HNC but were positive towards the use of such tools to improve decision making. HaNC-RC V2 was seen as a potential tool to facilitate a more holistic approach to assessing patient's symptoms, acting as a prompt to further explore a patient's presentation, requiring further investigation in this context. CONCLUSIONS: Community pharmacies offer access to patients and high-risk populations that could support HNC awareness initiatives, earlier identification and referral. However, further work to develop a sustainable and cost-effective approach to integrating pharmacists into cancer referral pathways is needed, alongside appropriate training for pharmacists to successfully deliver optimum patient care.

Population-based cohort study to assess the gingival lesions in 1319 patients with lichen planus.

AIMS: Oral lichen planus (OLP) is a chronic immune disease. In this paper, we evaluated the overall characters, clinical presentation, and outcome of gingival lesions in OLP Italian patients. METHODS AND RESULTS: A retrospective cohort study was accomplished: a total of 1319 charts were investigated, of whom 922 were female (69.9%): 617 patients (46.8%) manifested white lesions and 702 red ones (53.2%). While most patients had several oral sites of involvement, the gingiva was the unique location in 103 cases. Symptoms were reported in 480 patients (36.4%): 286 patients with erosive OLP, 103 with atrophic form, and 91 with a white form. Long-lasting surveillance showed that only 40 patients (3.03%) had a total clinical signs remission. Regarding OLP medical treatment provided, patients attending less frequently a dental office underwent more often a specific therapy. CONCLUSIONS: To the best of our knowledge, this is the biggest collections of patients with gingival OLP ever described; exclusive gingival lesions are, however, rare and unlikely to undergo a malignant transformation. Moreover, gum lesions seemed to anticipate the appearance of oral lesions and a higher rate of OLP therapy was observed in patients with less frequent dental check-ups and oral hygiene instructions.

Oral health status after hematopoietic stem cell transplantations: Outcomes from an adult Italian population.

AIM: To describe oral cavity changes in patients who underwent a hematopoietic stem cell transplantation (HSCT). METHODS AND RESULTS: A group of 32 patients was studied after a mean period of 48.8 months (±11.22) from HSCT; oral, dental, and periodontal status were collected and compared with those of healthy matched controls. Unstimulated whole salivary flow (UWS) and salivary pH were also measured. A validated questionnaire (EORTC QLQH&N-35) was used for reported quality of life. Fifty-nine percent of patients were affected by chronic graft-versus-host disease (cGVHD). Dental health and periodontal status were statistically worse than in controls (P = .003 and P = .008, respectively). Regarding the HSCT group, UWS was statistically lower, and EORTC QLQH&N-35 significantly higher than those reported in controls (P = .000 for both). There was no statistical correlation between hypo-salivation and conditioning, presence of cGVHD, type of medication used before and after transplantation, and time of follow-up. A reduction in salivary pH has been noted only for patients with erosive oral lesions. CONCLUSION: The oral cavity of HSCT patients appeared to undergo substantial modifications and the quality of life was deeply compromised.

Risk of Malignant Transformation in 3173 Subjects with Histopathologically Confirmed Oral Lichen Planus: A 33-Year Cohort Study in Northern Italy.

BACKGROUND: Oral lichen planus (OLP) is considered an oral potentially malignant disorder. The aim of our study was to estimate the risk for oral cancer in patients diagnosed with OLP. METHODS: A population-based cohort study between January 1988 and December 2020 at one hospital in Northern Italy was performed. The primary endpoint of the study was that of the histopathological diagnosis of oral cancer during the follow-up period. RESULTS: The study population comprised 3173 patients. During the follow-up period, 32 men and 50 women developed an oral squamous cell carcinoma (2.58%), with a mean time of 103.61 months after the initial diagnosis of OLP, and 21 patients died because of oral cancer. Almost half of the deceased patients had the last follow-up visit before cancer diagnosis in a period of more than 12 months. Older age, having a red form of OLP and fewer sites of involvement, increased the risk of having cancer, while age and no treatment increased the risk of death. CONCLUSION: This is the largest group of OLP patients with such a long follow up ever reported. Due to the increased risk of having a malignant transformation, especially in elderly subjects, OLP patients should be regularly followed up, particularly in the Northern Italian population.

The blue palate-A case series of imatinib-related oral pigmentation and literature review.

Pigmented oral mucosal lesions are diverse, and differential diagnosis can range from benign conditions such as oral melanotic macule to malignancies such as oral malignant melanoma. Imatinib mesylate is a tyrosine kinase inhibitor used as a first-line medication in the management of oncohematological conditions such as chronic myeloid leukemia and gastrointestinal stromal tumors. Side effects of imatinib therapy are common, and paradoxically imatinib has been associated with both hypo- and hyperpigmented lesions, the underlying mechanism for which is still unclear. Hyperpigmentation associated with imatinib therapy is a potentially underreported phenomenon. This article presents an in-depth, clinicopathological review of the literature surrounding imatinib-related hyperpigmentation, alongside a case series of imatinib-related oral pigmentation with notable practical learning points. A pragmatic flowchart to help clinicians in the diagnosis and management of oral pigmented lesions is provided, as well as advice on the application of the ABCDE criteria to standardize recording of oral pigmented lesions.

A service evaluation of the diagnostic testing for mucous membrane pemphigoid in a UK oral medicine unit.

BACKGROUND: Mucous membrane pemphigoid (MMP) is an uncommon bullous disease typically involving the oral cavity. The most commonly used laboratory test for the diagnosis of MMP is direct immunofluorescence (DIF) on fresh perilesional tissue; however, the sensitivity of this test may be hampered by technical difficulties. Immune-serological investigations can also be employed to render a diagnosis. The purpose of this paper was to present an evaluation of diagnostic testing for MMP within an Oral Medicine Unit in UK. METHODS: A retrospective analysis of the medical records was undertaken for patients who had undergone biopsy and DIF testing from January 2016 to December 2018. Parameters analysed included clinical presentation, histopathological features, DIF, salt-split skin indirect immunofluorescence, ELISA anti-BP180 and BP 230 and HLA-DQB1*03:01 findings. RESULTS: Thirty patients (23 females and 7 males, mean age 66.8 years old) were diagnosed with MMP through a combination of histopathology and serological testing. Sixteen patients (53%) were DIF positive, whereas in 14 (47%), MMP diagnosis was achieved using immune-serologic tests. HLA DQB1*03:01 status was undertaken in 15 DIF-positive and 12 DIF-negative patients, and HLA DQB1*03:01 was found in 73% and 58% of the cases, respectively. CONCLUSIONS: This service evaluation has shown that when DIF is informative, it remains the gold standard technique for diagnosis of MMP. However, we have also highlighted the value of serological testing for increasing diagnostic yield for patients with suspected MMP and the potential for HLA DQB1*03:01 as an adjunctive test for the evaluation of MMP.

Oral lichen planus: A disease or a spectrum of tissue reactions? Types, causes, diagnostic algorhythms, prognosis, management strategies.

Oral lichen planus and lichenoid lesions comprise a group of disorders of the oral mucosa that likely represent a common reaction pattern to 1 or more unknown antigens. The coexistence of hyperkeratotic striation/reticulation, varying degrees of mucosal inflammation from mild erythema to severe widespread ulceration, and a band-like infiltrate of mononuclear inflammatory cells including activated T lymphocytes, macrophages, and dendritic cells, are considered suggestive of oral lichen planus and lichenoid lesions. Several classification systems of oral lichen planus and lichenoid lesions have been attempted, although none seem to be comprehensive. In this paper, we present a classification of oral lichen planus and lichenoid lesions that includes oral lichen planus, oral lichenoid contact lesions, oral lichenoid drug reactions, oral lichenoid lesions of graft vs. host disease, discoid lupus erythematosus, and systemic lupus erythematosus, lichen planus-like variant of paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome, chronic ulcerative stomatitis, lichen planus pemphigoides, solitary fixed drug eruptions, and lichen sclerosus. We present the clinical and diagnostic aspects of oral lichen planus and lichenoid lesions, and discuss related treatment options.

Current protocols in the management of oral submucous fibrosis: An update.

Oral submucous fibrosis (OSMF) is a debilitating condition of oral cavity which has significant potential for malignant transformation. In spite of over 20 years of research, the pathogenesis of the condition is still obscure and no single management modality is effective. Many OSMF treatment protocols have been proposed to alleviate the signs and symptoms of the disorder and there is overwhelming evidence that as areca nut is primary cause, stopping its use may have a considerable effect on symptoms rather than reversing pre-existing fibrosis. We present a review of the current protocols for managing OSMF.

The Clinical Presentation of Oral Potentially Malignant Disorders.

Early detection of oral cancer improves survival rates significantly, however, the incidence of oral cancer has continued to rise in the UK - between 2002-2012, it increased by more than 30%. There is currently no national screening programme for oral cancer, so undertaking a full examination of the oral mucosa during routine dental appointments is vital. Although strong evidence is still lacking, oral cancer is thought to be preceded by oral potential malignant disorders (OPMDs) or oral precancerous diseases. These mainly present as white/red lesions within the mouth and their clinical appearance can be challenging to diagnose accurately, which can lead to them being misdiagnosed as negligible problems. Dentists must keep up to date with OPMDs detection and ensure they are capable of correctly recognising lesions that carry a potential risk. This paper aims to provide a brief overview on OPMDs, highlighting potentially malignant disorders as they may present to the practitioner, showing their typical clinical appearance, and suggesting differential diagnosis and clinical management in dental practice.

Oral purpura as the first manifestation of primary systemic amyloidosis.

Oral blood blisters and purpura are rare features of primary systemic amyloidosis (amyloid light-chain (AL) amyloidosis). We report a case in which these unusual presentations led to a diagnosis of amyloidosis, which enabled effective treatment before organ failure.

Clinical features and histological description of tongue lesions in a large Northern Italian population.

BACKGROUND: Only few studies on tongue lesions considered sizable populations, and contemporary literature does not provide a valid report regarding the epidemiology of tongue lesions within the Italian population. In this report, the histopathological and clinical appearance of 1.106 tongue lesions from northern Italians are described and discussed. MATERIAL AND METHODS: The case records of patients referred for the diagnosis and management of tongue lesions, from October 1993 to October 2013, were reviewed. Histological data were also obtained and blindly re-examined. RESULTS: For instance, a biopsy performed on a lingual ulcer has a strong predicting association with a carcinoma, whereas a biopsy on a white lesion predicts for a leukoplakia or oral lichen planus. Moreover, a biopsy of erosion is representative of bullous diseases, whereas a biopsy on a verrucous-papillary lesion is significant for fibroma. Furthermore, carcinomas occur in the majority of cases on the lingual edge or pelvis, oral lichen planus is mainly seen on the edge, and fibromas mostly on the lingual tip. CONCLUSIONS: The high frequency of tongue involvement of such different diseases emphasizes the importance of histological characterization and that some diseases occur more frequently than others, with a peculiar clinical aspect and a more common area. In fact our survey can help the clinician in advancing diagnostic hypothesis, on the basis of the elementary lesion and its site of involvement.

Oral manifestations of hepatitis C virus infection.

Extrahepatic manifestations (EHMs) of hepatitis C virus (HCV) infection can affect a variety of organ systems with significant morbidity and mortality. Some of the most frequently reported EHM of HCV infection, involve the oral region predominantly or exclusively. Oral lichen planus (OLP) is a chronic inflammatory condition that is potentially malignant and represents cell-mediated reaction to a variety of extrinsic antigens, altered self-antigens, or super antigens. Robust epidemiological evidence support the link between OLP and HCV. As the virus may replicate in the oral mucosa and attract HCV-specific T lymphocytes, HCV may be implicated in OLP pathogenesis. Sjögren syndrome (SjS) is an autoimmune exocrinopathy, characterized by dryness of the mouth and eyes and a multitude of other systemic signs and symptoms. SjS patients have also an increased risk of non-Hodgkin lymphoma. Patients with chronic hepatitis C do frequently have histological signs of Sjögren-like sialadenitis with mild or even absent clinical symptoms. However, it is still unclear if HCV may cause a disease mimicking SjS or it is directly responsible for the development of SjS in a specific subset of patients. Oral squamous cell carcinoma is the most common oral malignant tumour and at least in some part of the world could be linked to HCV.

Changes in parotid gland morphology and function in patients treated with intensity-modulated radiotherapy for nasopharyngeal and oropharyngeal tumors.

OBJECTIVE: To evaluate the morphological changes of the parotid glands in patients treated with intensity-modulated radiotherapy (IMRT) for nasopharyngeal and oropharyngeal tumors and the correlations with parotid function. METHODS: Ten patients with nasopharyngeal and oropharyngeal tumors treated with IMRT between May 2009 and January 2010 at Hokkaido University Hospital were included in this study. In the morphological assessment of the parotid glands, the sizes and computed tomography (CT) numbers of the bilateral parotid glands before and after IMRT with CT were calculated. For functional assessment of the parotid glands, we conducted the Saxon test and used a visual analog scale (VAS) for xerostomia evaluation. RESULTS: Reductions in saliva secretion were observed in the patients treated with IMRT for nasopharyngeal and oropharyngeal tumors, and there was a significant correlation between the reduction in saliva secretion and the VAS. The reductions in the parotid gland size and CT number were larger on the ipsilateral side than on the contralateral side. The reduction in saliva secretion was not significantly correlated with the reduction in parotid gland size, but was significantly correlated with the reduction in CT number. CONCLUSIONS: Morphological and functional changes of the parotid glands were observed after IMRT for nasopharyngeal and oropharyngeal tumors, and preservation of the contralateral parotid glands was only partly achieved. Among the morphological changes of the parotid glands, the CT number may be considered a predictor of parotid function after radiotherapy.

Oral lichenoid tissue reactions: diagnosis and classification.

The concept of lichenoid tissue reaction/interface dermatitis was introduced in dermatology to define a number of diverse inflammatory skin diseases linked together by the presence of common histopathological features. Similarly to the skin, the oral mucosa is affected by a variety of oral lichenoid lesions. Oral LTRs (OLTRs) include: oral lichen planus; oral lichenoid contact lesion; oral lichenoid drug reaction; oral lichenoid lesions of graft-versus-host disease; oral discoid lupus erythematosus; oral lesions of systemic lupus erythematosus; erythema multiforme; paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome; chronic ulcerative stomatitis and lichen planus pemphigoid. Traditionally, diagnosis of OLTRs relies on clinical and histological correlation but in several instances this approach fails to provide a reliable diagnosis. Inclusion of molecular techniques may refine our ability to differentiate OLTRs.

Numb chin syndrome as first symptom of diffuse large B-cell lymphoma.

Numb chin syndrome is a rare sensory neuropathy of the mental nerve characterized by numbness, hypoesthesia, paraesthesia, and very rarely pain. Dental causes, especially iatrogenic ones, maxillofacial trauma, or malignant neoplasm are etiologic factors for this rare syndrome. Many malignant and metastatic neoplasms are causing this syndrome, like primary osteosarcoma, squamous cell carcinoma, and mandibular metastasis of primary carcinoma of breast, lung, thyroid, kidney, prostate, and nasopharynx. Haematological malignancies like acute lymphocytic leukaemia, Hodgkin and non-Hodgkin lymphoma, and myeloma can cause this neuropathy. The authors report a case of a 71-year-old woman in which the numb chin syndrome was the first symptom of the diffuse large B-cell lymphoma, which caused infiltration and reabsorption of the alveolar ridge and lower mandibular cortex. A biopsy of the mass was performed on fragments of tissue collected from the mandibular periosteum, medullary and cortical mandibular bone, and inferior alveolar nerve.

Clinical and histological features of gingival lesions: a 17-year retrospective analysis in a northern Italian population.

OBJECTIVES: Only few studies on gingival lesions considered large enough populations and contemporary literature does not provide a valid report regarding the epidemiology of gingival lesions within the Italian population. The histopathological and clinical appearance of 538 gingival lesions from northern Italians are described and discussed here. STUDY DESIGN: The case records of patients referred for the diagnosis and management of gingival lesions, from October 1993 to October 2009, were reviewed. Data regarding the histological type of lesion were also obtained from the biopsy register for each case, and blindly re-examined. RESULTS: We reported a greater frequency of benign lesions (reactive and/or inflammatory) in non-plaque/non-calculus induced gingival disorders. We confirmed an unambiguous prevalence of oral squamous cell carcinoma above all other malignant neoplasia, and a prevalence of neoplastic malignant lesions in the maxilla, with a slight increase in females and a drift of the incidence peak from the seventh to the eighth decade. There was a prevalence of precancerous gingival lesions in the maxilla, with a higher incidence in females and with a drift from the sixth to the seventh decade. We also reported a prevalence of oral lichen planus and lichenoid lesions as major manifestations of desquamative gingivitis. CONCLUSIONS: The high frequency of gingival involvement of such different diseases emphasizes the importance of histological characterization and differential diagnosis for periodontists, but more prospective studies are needed to better describe the true incidence of the non-plaque related gingival diseases.

Interventions for treating oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a common chronic autoimmune disease associated with cell-mediated immunological dysfunction. Symptomatic OLP is painful and complete healing is rare. OBJECTIVES: To assess the effectiveness and safety of any form of therapy for symptomatic OLP. SEARCH STRATEGY: The following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 26 January 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 26 January 2011) and EMBASE via OVID (1980 to 26 January 2011). There were no restrictions regarding language or date of publication. SELECTION CRITERIA: All randomised controlled clinical trials (RCTs) of therapy for symptomatic OLP which compared treatment with a placebo or between treatments or no intervention were considered in this review. DATA COLLECTION AND ANALYSIS: The titles and abstracts of all reports identified were scanned independently by two review authors. All studies meeting the inclusion criteria were assessed for risk of bias and data were extracted. For dichotomous outcomes, the estimates of effects of an intervention were expressed as risk ratios (RR) together with 95% confidence intervals. For continuous outcomes, mean differences (MD) and 95% confidence intervals were used to summarise the data for each group. The statistical unit was the patient. Meta-analyses were done only with studies of similar comparisons reporting the same outcome measures. MAIN RESULTS: 28 trials were included in this review. Pain is the primary outcome of this review because it is the indication for treatment of OLP, and therefore this review indicates as effective, only those treatments which significantly reduce pain. Although topical steroids are considered first line treatment for symptomatic OLP, we identified no RCTs that compared steroids with placebo. There is no evidence from the three trials of pimecrolimus that this treatment is better than placebo in reducing pain from OLP. There is weak evidence from two trials, at unclear and high risk of bias respectively, that aloe vera may be associated with a reduction in pain compared to placebo, but it was not possible to pool the pain data from these trials. There is weak and unreliable evidence from two small trials, at high risk of bias, that cyclosporin may reduce pain and clinical signs of OLP, but meta-analysis of these trials was not possible.There were five trials that compared steroids with calcineurin inhibitors, each evaluating a different pair of interventions. There is no evidence from these trials that there is a difference between treatment with steroids compared to calcineurin inhibitors with regard to reducing pain associated with OLP. From six trials there is no evidence that any specific steroid therapy is more or less effective at reducing pain compared to another type or dose of steroid. AUTHORS' CONCLUSIONS: Although topical steroids are considered to be first line treatment, we identified no RCTs that compared steroids with placebo in patients with symptomatic OLP. From the trials in this review there is no evidence that one steroid is any more effective than another. There is weak evidence that aloe vera may reduce the pain of OLP and improve the clinical signs of disease compared to placebo. There is weak and unreliable evidence that cyclosporin may reduce pain and clinical signs of OLP. There is no evidence that other calcineurin inhibitors reduce pain compared to either steroids or placebo. From the 28 trials included in this systematic review, the wide range of interventions compared means there is insufficient evidence to support the effectiveness of any specific treatment as being superior.

Immunohistochemical expression of basement membrane proteins of verrucous carcinoma of the oral mucosa.

Squamous cell carcinoma (SCC) of the oral cavity is an extremely invasive tumour of stratified squamous epithelium that spreads throughout degradation of the basement membrane (BM) and extra-cellular matrix. Oral verrucous carcinoma (VC) is a rare low-grade variant of oral SCC that penetrates into the subepithelial connective tissue. It also has a different clinical behaviour from classical oral SCC. We investigated the immunohistochemical expression of laminin, laminin-5, collagen IV and fibronectin in VC, severe epithelial dysplasia (SED) and SCC in order to analyse if the pattern of these molecules expression contributes to the differences in the biological behaviour of these diseases. The staining pattern of laminin was less intensive in SCC compared with SED and VC, and collagen IV expression was increased in VC compared with SED. Discontinuities of laminin, collagen IV and fibronectin were more evident in SED than in VC. This study indicates that VC has a biological behaviour different from SED or SCC, observable by immunohistochemistry in the BM zone.