Michael J. Veness

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.

Surgery and adjuvant radiotherapy in patients with cutaneous head and neck squamous cell carcinoma metastatic to lymph nodes: combined treatment should be considered best practice.

Objective: Patients with cutaneous squamous cell carcinoma (SCC) may develop metastatic SCC to nodes in the head and neck. Recent data support best outcome with the addition of adjuvant radiotherapy. This study aims to present further supportive evidence.

Aggressive cutaneous malignancies following cardiothoracic transplantation

The development of malignancies in recipients of a cardiothoracic transplant (CTT)—that is, heart, lung, or heart and lung recipients—is of concern. Cutaneous and lymphoproliferative malignancies comprise the two major groups of malignancies encountered. A small subgroup of patients will develop potentially life‐threatening aggressive cutaneous malignancies (ACM); these are poorly defined and documented in the literature. The authors report the results for 619 CTT recipients from a single institution.

High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck Results from 266 Treated Patients with Metastatic Lymph Node Disease

Most patients with cutaneous squamous cell carcinoma (cSCC) of the head and neck (HN) are at low‐risk (< 5%) of developing metastatic SCC to regional lymph nodes. However, patients with unfavorable clinicopathologic factors often are under appreciated by clinicians but remain at higher risk for developing metastatic lymph node disease and dying.

Cutaneous head and neck squamous cell carcinoma metastatic to parotid and cervical lymph nodes

Nonmelanoma skin cancers occur at an epidemic rate in Australia and are increasing in incidence worldwide. In most patients, local treatment is curative. However, a subset of patients will be diagnosed with a high‐risk cutaneous squamous cell carcinoma (SCC) and are defined as patients at increased risk of developing metastases to regional lymph nodes. Patients with high‐risk SCC may be identified based on primary lesion and patient factors. Most cutaneous SCC arises on the sun‐exposed head and neck. The parotid and upper cervical nodes are common sites for the development of metastases arising from ear, anterior scalp, temple/forehead, or scalp SCC. The mortality and morbidity associated with high‐risk cutaneous SCC is usually a consequence of uncontrolled metastatic nodal disease and, to a lesser extent, distant metastases. Patients with operable nodal disease have traditionally been recommended for surgery. The efficacy of adjuvant radiotherapy has previously been questioned based on weak evidence in the early literature. Recent evidence from larger studies has, however, strengthened the case for adjuvant radiotherapy as a means to improve locoregional control and survival. Despite this, many patients still experience relapse and die. Research aimed at improving outcome such as a randomized trial incorporating the addition of chemotherapy to adjuvant radiotherapy is currently in progress in Australia and New Zealand. Ongoing research also includes the development of a proposed new staging system and investigating the role of molecular factors such as the epidermal growth factor receptor.

MERKEL CELL CARCINOMA: IMPROVED OUTCOME WITH ADJUVANT RADIOTHERAPY

Background:  Merkel cell carcinoma is an aggressive primary cutaneous neuroendocrine carcinoma. Patients remain at high risk of locoregional and distant relapse despite treatment. Most studies support the incorporation of locoregional adjuvant radiotherapy in reducing the risk of relapse.

Merkel cell carcinoma of the head and neck: Is adjuvant radiotherapy necessary?

Controversy exists regarding the optimal management of patients with Merkel cell carcinoma. The primary aim of this study was to determine whether combined treatment with surgery and radiotherapy improves outcome in a multi‐institutional cohort of patients with Merkel cell carcinoma of the head and neck. The secondary aims were to determine by stage, which patients derive benefit from combined therapy and to identify predictors for survival on multivariable analysis.

Improving interpretation of clinical studies by use of confidence levels, clinical significance curves, and risk-benefit contours

The process of interpreting the results of clinical studies and translating them into clinical practice is being debated. Here we examine the role of p values and confidence intervals in clinical decision-making, and draw attention to confusion in their interpretation. To improve result reporting, we propose the use of confidence levels and plotting of clinical significance curves and risk-benefit contours. These curves and contours provide degrees of probability of both the potential benefit of treatment and the detriment due to toxicity. Additionally, they provide clinicians with a mechanism of translating the results of studies into treatment for individual patients, thus improving the clinical decision-making process. We illustrate the application of these curves and contours by reference to published studies. Confidence levels, clinical significance curves, and risk-benefit contours can be easily calculated with a hand calculator or standard statistical packages. We advocate their incorporation into the published results of clinical studies.

Implications for Clinical Staging of Metastatic Cutaneous Squamous Carcinoma of the Head and Neck Based on a Multicenter Study of Treatment Outcomes

Cutaneous squamous cell carcinoma (SCC) of the head and neck is a common cancer that has the potential to metastasize to lymph nodes in the parotid gland and neck. Previous studies have highlighted limitations with the current TNM staging system for metastatic skin carcinoma. The aim of this study was to test a new staging system that may provide better discrimination between patient groups.

Cutaneous head and neck squamous cell carcinoma metastatic to cervical lymph nodes (nonparotid): a better outcome with surgery and adjuvant radiotherapy.

Objective: The aim of this study is to report on the experience of treating cutaneous squamous cell carcinoma (SCC) metastatic to cervical (nonparotid) lymph nodes at the Head and Neck Unit, Westmead Hospital, Sydney, Australia. Study Design: Retrospective chart review. Methods: Patients diagnosed with previously untreated metastatic cutaneous SCC to cervical lymph nodes (levels I‐V) and treated with radiotherapy, surgery, or surgery and adjuvant radiotherapy were identified. Relapse and outcome was analyzed using Cox regression analysis. Results: Between 1980 and 2000, 74 patients were treated with curative intent. There were 59 males and 15 females, with a median age of 66 (range 37–93) years. Median duration of follow up was 48 (range 12–187) months. Fifty‐two were treated with neck dissection and radiotherapy, 13 with neck dissection alone, and 9 with only radiotherapy. Most patients (85%) had an identifiable index lesion. Level I (38%) and II (36%) lymph nodes were the most often involved. In total, 25 (34%) patients developed recurrent disease, predominantly locoregional (22 of 25). Median time to recurrence was 5.2 (2‐34.3) months. Increasing nodal size (≥3cm) (P = .01), metastatic spread to multiple nodes (P = .05), and the presence of extranodal spread (P = .01) all predicted for worse survival. Patients undergoing combined modality treatment had a lower relapse rate (15%) and a significantly better disease free survival (P = .001) compared with single modality treatment. Conclusion: Metastatic cutaneous SCC is uncommon but potentially lethal. Surgery and adjuvant radiotherapy remain the best practice and provide the best chance of achieving locoregional control.