Edward McNeil

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.

Significance of clinical stage, extent of surgery, and pathologic findings in metastatic cutaneous squamous carcinoma of the parotid gland†

Metastatic cutaneous cancer is the most common parotid malignancy in Australia, with metastatic squamous carcinoma (SCC) occurring most frequently. There are limitations in the current TNM staging system for metastatic cutaneous malignancy, because all patients with nodal metastases are simply designated N1, irrespective of the extent of disease. The aim of this study was to analyze the influence of clinical stage, extent of surgery, and pathologic findings on outcome after parotidectomy for metastatic SCC by applying a new staging system that separates metastatic disease in the parotid from metastatic disease in the neck.

Influence of condition of surgical margins on local recurrence and disease-specific survival in oral and oropharyngeal cancer

BACKGROUND The clearance of surgical margins at the primary site is widely thought to influence the subsequent course of the disease in patients operated on for oral and oropharyngeal carcinoma. In some reports the adverse impact of close or involved margins was not negated by postoperative radiotherapy. These findings, in addition to descriptive histopathological studies, have led some authors to recommend margins of more than a macroscopic clearance of 1cm at certain subsites. We have therefore examined the relation between the condition of surgical margins and local recurrence and disease-specific survival. METHODS Identical treatment protocols were used to treat two independent groups of patients (Sydney, Australia, n=237; Lanarkshire, n=95) who presented with previously untreated carcinoma of the mouth or oropharynx. All patients were operated on with the primary objective of achieving a macroscopic clearance of 1cm. Postoperative radiotherapy was used according to a protocol. Data about patients were entered into comprehensive computerised databases prospectively. Known clinical and pathological prognostic indicators, in addition to the condition of surgical margins, were analysed to find out if they were predictive of local recurrence and disease-specific survival using the Cox proportional hazard model. RESULTS Local recurrence was predicted by the presence of perineural invasion at the primary site in both groups. Disease-specific survival was predicted by the presence and extent of regional lymph node metastases in both groups. The condition of surgical margins (clear, close, or involved) did not predict local recurrence, or disease-specific survival on multivariate analysis. CONCLUSIONS A macroscopic margin of 1cm seems adequate in the surgical management of oral and oropharyngeal carcinoma. For most patients who have close or involved margins the biology of the disease influences the subsequent course irrespective of the width of clearance of tumour.

Tumor thickness influences prognosis of T1 and T2 oral cavity cancer—but what thickness?

Previous studies have demonstrated that tumor thickness might influence prognosis in oral cancer, but the significant point at which outcome changes has varied from 1.5 mm to 6 mm. The clinical relevance of thickness remains unclear, and a reproducible prognostic “breakpoint” needs to be defined.

Childhood Acute Renal Failure: 22-Year Experience in a University Hospital in Southern Thailand

OBJECTIVES. The objectives of this study were to review the prevalence, cause, and morbidity and mortality rates of acute renal failure in a large tertiary care institution in southern Thailand, to examine any differences in acute renal failure cases diagnosed during a 22-year period, and to determine the risk factors indicating death. METHODS. The case records for children 1 month to 17 years of age who were diagnosed as having acute renal failure between February 1982 and December 2004, in the Department of Pediatrics, Songklanagarind Hospital, in southern Thailand, were reviewed. RESULTS. A total of 311 children with 318 episodes of acute renal failure were included, that is, 177 boys (55.7%) and 141 girls (44.3%), 1 month to 16.7 years of age (mean age: 7.6 ± 5.1 years; median age: 7.8 years). The causes of acute renal failure in each age group were significantly different. Overall, sepsis was the major cause of acute renal failure, accounting for 68 episodes (21.4%), followed by hypovolemia, poststreptococcal glomerulonephritis, systemic lupus erythematosus, and infectious diseases. Renal replacement therapy was performed in 55 cases (17.3%). The overall mortality rate was 41.5%. Logistic regression analysis showed that disease groups and creatinine levels were significant independent predictors of outcomes. CONCLUSIONS. The incidence of acute renal failure in Songklanagarind Hospital was 0.5 to 9.9 cases per 1000 pediatric patients, with a mortality rate of 41.5%. Sepsis was a major cause of acute renal failure and death. Causes of acute renal failure and serum creatinine levels were significant independent predictors of death.

Primary and Metastatic Cancer of the Parotid: Comparison of Clinical Behavior in 232 Cases

Objectives/Hypothesis Parotid malignancy may develop as a primary cancer of salivary tissue or by metastatic involvement of parotid lymph nodes. The aim of the study was to compare the clinical behavior of primary and metastatic parotid cancers by analyzing patterns of treatment failure and clinical outcomes.

The Expression Of Key Cell Cycle Markers And Presence Of Human Papillomavirus In Squamous Cell Carcinoma Of The Tonsil.

Chemical carcinogens induce squamous cell carcinoma (SCC) of the head and neck by targeting the p53 and the retinoblastoma (pRb) pathways. Human papillomavirus (HPV) might have an etiologic role in these cancers at particular sites. Few studies have compared cell cycle protein expression in HPV‐positive and HPV‐negative tumors in this region.

Influence of bone invasion and extent of mandibular resection on local control of cancers of the oral cavity and oropharynx.

The aim of this paper was to evaluate the influence of bone invasion on treatment outcome among patients with cancers of the oral cavity and oropharynx and to determine whether or not outcome was influenced by the extent of mandibular resection. A review of 127 prospectively documented patients who were treated with marginal or segmental resection for oral (n = 110) and oropharyngeal (n = 17) cancers was undertaken. There were 97 males and 30 females with a median age of 61 years. Clinical T stages were: T1 17 patients, T2 33, T3 22, T4 55. Median followup was 4 years. A total of 94 patients underwent marginal resections and 33 underwent segmental resections. Histological bone invasion was present in 17 patients (16%) in the marginal resection group and 21 patients (64%) in the segmental group (P<0.05). Soft tissue surgical margins were positive in 11 patients (12%) in the marginal group and in seven patients (21%) in the segmental group (P=not significant). Local control did not correlate significantly with T stage, the extent of mandibular resection or the presence of histological bone invasion, but was significantly influenced by positive soft tissue margins (P<0.01). Among patients with bone invasion, the local control rate was higher following segmental resection when compared to marginal resections (87% vs 75%) but this was not statistically significant. Survival was significantly influenced by positive soft tissue margins but not bone invasion or the type of resection. We conclude that bone invasion alone did not predict for local control or survival rates among patients with oral and oropharyngeal cancers. Involved soft tissue margins were highly predictive of local recurrence and decreased survival. Conservative resection of the mandible is safe as long as marginal mandibulectomy does not lead to compromise of soft tissue margins. Segmental resection should be reserved for patients extensive bone invasion or those with limited invasion in a thin atrophic mandible.

Outcome of treatment for advanced cervical metastatic squamous cell carcinoma

Patients with advanced cervical metastases from mucosal squamous cell carcinoma have a poor prognosis because of their high risk of regional and distal failure. This study aims to evaluate the outcomes of patients with clinical N2 or N3 disease managed with surgery and postoperative radiotherapy.

Absence of human papillomavirus in tonsillar squamous cell carcinomas from Chinese patients.

Epidemiological and experimental evidence from Western countries now consistently support an etiological role for human papillomavirus (HPV) in a subset of oropharyngeal squamous cell carcinomas (SCC), especially those originating in the tonsil. The role of HPV in the etiology of tonsil cancer in developing countries such as China has not been investigated. In this study, none of 16 tonsil cancer specimens from Chinese patients were positive for HPV DNA, whereas those from Australian patients using the same methodology gave a positivity rate of 46%. The tumors from Chinese patients, like the Australian HPV-negative subset, significantly overexpressed pRb and cyclin D1 and underexpressed p16(INK4A) (p16). In contrast, the Australian HPV-positive cancers overexpressed p16 and had reduced expression of pRb and cyclin D1. These findings may help explain why China has a relatively low rate of oropharyngeal cancer compared with Australia. They also support the hypothesis that molecular pathways to tonsil cancer mediated by HPV are distinct from those induced by mutagens present in cigarette smoke or alcohol.