Different cellular p16(INK4a) localisation may signal different survival outcomes in head and neck cancer.

BACKGROUND: Recently, the management of head and neck squamous cell carcinoma (HNSCC) has focused considerable attention on biomarkers, which may influence outcomes. Tests for human papilloma infection, including direct assessment of the virus as well as an associated tumour suppressor gene p16, are considered reproducible. Tumours from familial melanoma syndromes have suggested that nuclear localisation of p16 might have a further role in risk stratification. We hypothesised p16 staining that considered nuclear localisation might be informative for predicting outcomes in a broader set of HNSCC tumours not limited to the oropharynx, human papilloma virus (HPV) status or by smoking status. METHODS: Patients treated for HNSCC from 2002 to 2006 at UNC (University of North Carolina at Chapel Hill) hospitals that had banked tissue available were eligible for this study. Tissue microarrays (TMA) were generated in triplicate. Immunohistochemical (IHC) staining for p16 was performed and scored separately for nuclear and cytoplasmic staining. Human papilloma virus staining was also carried out using monoclonal antibody E6H4. p16 expression, HPV status and other clinical features were correlated with progression-free (PFS) and overall survival (OS). RESULTS: A total of 135 patients had sufficient sample for this analysis. Median age at diagnosis was 57 years (range 20-82), with 68.9% males, 8.9% never smokers and 32.6% never drinkers. Three-year OS rate and PFS rate was 63.0% and 54.1%, respectively. Based on the p16 staining score, patients were divided into three groups: high nuclear, high cytoplasmic staining group (HN), low nuclear, low cytoplasmic staining group (LS) and high cytoplasmic, low nuclear staining group (HC). The HN and the LS groups had significantly better OS than the HC group with hazard ratios of 0.10 and 0.37, respectively, after controlling for other factors, including HPV status. These two groups also had significantly better PFS than the HC staining group. This finding was consistent for sites outside the oropharynx and did not require adjustment for smoking status. CONCLUSION: Different p16 protein localisation suggested different survival outcomes in a manner that does not require limiting the biomarker to the oropharynx and does not require assessment of smoking status.

Gene therapy principles and strategies for head and neck cancer.

The ongoing preclinical and now human clinical investigation of gene therapy in head and neck cancer and cancer and cancer overall have provided a few foundation points of information. The first point is that viral and nonviral gene therapy has demonstrated efficacy in a variety of animal models and these successes support consideration and evaluation of gene therapy in human clinical trials. Regarding the retrovirus as a vehicle for gene transfer in humans, it appears to be a safe vehicle. There has been no significant short- or long-term toxicity associated with a wide application of retroviral gene therapy in human patients [12]. Regarding adenovirus as a vehicle, there are less numbers and less advanced trials, but the associated toxicities reported thus far have been both transient and relatively minor. Nonviral cationic lipid-mediated gene transfer also appears safe in human patients. These points are significant because they establish the safety foundation for delivering potentially therapeutic genes to humans. Without this safety data, gene therapy would not have a future in the treatment of cancer. At the present Phase I stage of human clinical trial investigation for head and neck cancer, the focus remains on patients with advanced or recurrent incurable cancer. Although this patient population is a standard choice for establishing the safety of novel therapies, the greatest chance of eventual success with currently available gene transfer vehicles and gene therapy strategies will most likely be in those patients with less advanced stages of disease. Another future potential for gene therapy in head and neck cancer may be in combination with surgery or radiation or chemotherapy. At some acceptable ratio of efficacy to toxicity, gene therapy may also prove effective against earlier stage cancer either as a primary or adjuvant therapy. In conjunction with the evolution of molecular diagnostics, gene therapy strategies may provide the means for preventing the malignant progression of premalignant head and neck lesions upon early diagnosis.

Assessment of donor-site functional morbidity from radial forearm fasciocutaneous free flap harvest.

OBJECTIVE: To quantitate the functional morbidity to the hand and wrist following harvest of a radial forearm fasciocutaneous free flap. DESIGN: Prospective case-control study, with each patient providing his or her internal control, comparing preoperative and postoperative operated to nonoperated forearms. SETTING: Tertiary care hospital in large metropolitan area. PATIENTS: A consecutive sample of 11 patients who underwent a radial forearm free flap reconstruction of the head and neck from April 1997 to May 1998. MAIN OUTCOME MEASURES: Range of motion of the wrist (flexion and extension, ulnar and radial deviation), grip and pinch strength, and sharp and dull sensation in the distribution of the radial, ulnar, and median nerves. RESULTS: Statistically significant differences (P<.05) were measured in wrist flexion, pinch strength, and sharp sensation in the anatomical snuffbox of the operated forearm. No subjective complaints of loss of function were reported by any patient. CONCLUSIONS: Donor-site functional morbidity associated with harvest of the radial forearm fasciocutaneous free flap is measurable. The statistical differences found do not translate into subjective patient complaints of everyday functional morbidity.