D. Murray Walker

Human papillomavirus positivity predicts favourable outcome for squamous carcinoma of the tonsil

Mutations in the p53 and retinoblastoma (pRb) pathways associated with the use of tobacco and alcohol are common in squamous cell carcinoma (SCC) of the head and neck. Cell cycle proteins are also affected by human papillomavirus (HPV), which may also have an aetiological role in cancers at particular sites, most notably the tonsil. Attempts to identify prognostic molecular markers in head and neck cancers have met with conflicting results, but few studies have been undertaken with tumours of known HPV status at a single anatomic site. In our study 86 tonsil cancers were analysed for HPV status by sequence analysis of polymerase chain reaction products and for the expression of cell cycle proteins (p53, p21CIP1/WAF1, pRb, p16INK4A, cyclin D1 and p27KIP1) by immunohistochemistry. The HPV status could be established in 67 of the tumours. Thirty‐one (46%) of these were HPV‐positive, predominantly (28/31) for HPV16. Findings were related to tumour recurrence and patient survival. None of the cell cycle proteins independently predicted recurrence or survival. Patients with HPV‐positive tumours, however, were significantly less likely (p < 0.05) to have recurrence or to die of disease than those with HPV‐negative tumours, after adjusting for the effects of the cell cycle proteins, clinical stage, pathological node status, tumour grade, age, gender and treatment. These findings support the concept that HPV‐positive tonsil cancers may be a distinct biological group with less aggressive characteristics. Screening of tonsil cancers for HPV DNA may help optimise treatment and provide more accurate prognostic information.

The pathology of oral cancer

Summary Oral cancer is a serious public health problem, with over 200 000 new cases reported annually worldwide, two‐thirds of which occur in developing countries. The overall mortality rate for intra‐oral cancer remains high at approximately 50%, even with modern medical services, probably due to the advanced stage of the disease at presentation. This review outlines recent advances in our understanding of the roles and interactions of major risk factors for oral cancer worldwide, notably tobacco, alcohol and betel quid and the genetic polymorphisms determining their metabolism that may predispose patients to oral carcinoma. Oral epithelial lesions with malignant potential are described. We discuss the histopathology of oral cancer, its grading and the staging of the disease at clinical, microscopic, immunohistological and molecular levels. A recommended minimum dataset for pathology reports is described. The available strategies and current prospects for controlling oral cancer in the community are summarised.

Establishing a normal range for mouth opening : its use in screening for oral submucous fibrosis

The maximal mouth opening of 700 healthy Nepalese adults, age range of 18-68 years, measured by paraclinical workers was determined as there are no data available for an Asian population. The mean value of the inter-incisal distance was 47.1 mm (range 33.7-60.4 mm) and 98% of the population surveyed fell within this range. The minimum limit of normal oral opening was determined to be 34 mm. Ten out of 13 patients with histologically confirmed oral submucous fibrosis (OSF) had a maximal oral opening of less than 34 mm. It was concluded that reduced oral opening measured by paraclinical workers as a single screening test for oral submucous fibrosis, has a sensitivity of only 77% and will detect only advanced cases. However, each of the 3 subjects from the healthy population found to have restricted mandibular opening and who agreed to be examined further had significant oral conditions, namely oral submucous fibrosis (2) and pericoronitis (1). The study confirms the value of this measurement as a screening procedure for significant oral disease by paraclinical staff particularly in developing countries where trained dental and medical personnel are scarce. Because of its limited sensitivity, measurement of mouth opening is unsatisfactory as a single screening test for OSF, as it will not detect early stages of the disease.

Spatial distribution of lead in enamel and coronal dentine of wistar rats.

Lead is one of the most hazardous environmental toxins known. The assessment of lead in dental hard tissues is important in the understanding of its to xic effects on oral tissues and in estimating exposure and body burden in individuals exposed to lead from the environment. However, current information on the uptake and distribution of lead in enamel and dentine is limited. The aim of this project was to study, at high resolution, the spatial distribution of lead in enamel and coronal dentine using an experimental rat model. A dose of 40 mg/L of lead nitrate was administered to pregnant femake rats during the periods of gestation and lactation through drinking water. First mandibular molar teeth were removed from their 15-d-old pups and the distribution of lead was studied using a nuclear microprobe (NMP). The distribution of lead in enamel and coronal dentine showed four distinct zones with significantly different mean lead concentrations (p<0.05). High levels of lead were observed in the superficial regions of enamel and in the dentine directly adjacent to the pulp. Additionally, the results confirmed that the NMP is capable of mapping the distribution of lead in teeth at micron resolutions with a detection limit of approx 1 μg/g.

Massive osteolysis of the mandibleReport of a case with multifocal bone loss

Osteolysis of the jaws has been reported in association with infection, cysts, neoplasia, and metabolic, endocrine, or hematologic abnormalities. Rare cases of idiopathic osteolysis have also been recorded. We report the case of a 10-year-old girl with mandibular basal and alveolar bone resorption that has continued over a period of 9 years. The patient has subsequently developed bilateral resorption of the ascending rami and condyles. The maxilla is uninvolved. Investigations included radiology, computerized tomography, scintigraphy, hematology, serum chemistry, endocrinology, histopathology, microbiology, and immunology. Neutrophil chemotaxis, chemiluminescence, and random migration values were low but within the normal range. These findings are interpreted as indicating an unusual variant of massive osteolysis.

Fatal Staphylococcus aureus infective endocarditis: the dental implications.

Infective endocarditis remains an important and life-threatening infection despite improvements in diagnosis and management. There is currently a greater role for nosocomial acquisition of organisms and immunosuppression in the pathogenesis of this disease and emergence of a broader spectrum of infective organisms including those not commonly isolated from the mouth such as staphylococci. We report a case of infective endocarditis caused by Staphylococcus aureus in which the patient developed disseminated intravascular coagulation and multiple septic infarcts resulting in a frontal lobe brain abscess. Multiple dental extractions were complicated by delayed postextraction hemorrhage and the immediate cause of death was abdominal hemorrhage. The dental management in infective endocarditis should be planned in consultation with the attending physician, and should take into account both the causative organism and the presence of complications. When the oral cavity cannot be proven as the bacterial source for infective endocarditis, the immediate dental management should be directed toward improving the patients oral hygiene and providing pain relief. Definitive long-term treatment, including any extractions, is ideally delayed until the patient has fully recovered from the infective endocarditis and its attendant complications.

Analysis of the amplification refractory mutation allele-specific polymerase chain reaction system for sensitive and specific detection of p53 mutations in DNA

The sensitivity of the amplification refractory mutation allele‐specific polymerase chain reaction system (ARMAS‐PCR) to detect known p53 mutations was determined using DNA extracted from two human tumour cell lines collected by cytobrush, as a model for its use in exfoliative cytology. Using DNA extracted from SW480 and CEM cell lines diluted with normal human fibroblasts, a nested ARMAS‐PCR was more sensitive than a non‐nested version and could detect one mutated cell amongst 100 000 normal cells. When compared with PCR–single stranded conformational polymorphism, nested ARMAS‐PCR was 10 000 times more sensitive for detecting mutant p53 in extracted DNA. Primer design proved to be influential on the sensitivity and specificity of the assay; increased specificity was achieved by the use of deliberate mismatches upstream from the 3′ end of mutation‐specific primers. ARMAS‐PCR was confirmed to be specific for the mutation that each primer was designed to detect. Nested ARMAS‐PCR offered a rapid and sensitive method of analysis of cells with predetermined p53 mutations and has the potential to be applied to the study of the molecular progression of cancer, including diagnosis and detection of residual disease. It could also be extended to the in situ detection of aberrant cells. Copyright