Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer.

BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal cancer (OPSCC) is associated with improved survival compared with HPV-negative disease. However, a minority of HPV-positive patients have poor prognosis. Currently, there is no generally accepted strategy for identifying these patients. METHODS: We retrospectively analysed 270 consecutively treated OPSCC patients from three centres for effects of clinical, pathological, immunological, and molecular features on disease mortality. We used Cox regression to examine associations between factors and OPSCC death, and developed a prognostic model for 3-year mortality using logistic regression analysis. RESULTS: Patients with HPV-positive tumours showed improved survival (hazard ratio (HR), 0.33 (0.21-0.53)). High levels of tumour-infiltrating lymphocytes (TILs) stratified HPV-positive patients into high-risk and low-risk groups (3-year survival; HPV-positive/TIL(high)=96%, HPV-positive/TIL(low)=59%). Survival of HPV-positive/TIL(low) patients did not differ from HPV-negative patients (HR, 1.01; P=0.98). We developed a prognostic model for HPV-positive tumours using a 'training' cohort from one centre; the combination of TIL levels, heavy smoking, and T-stage were significant (AUROC=0·87). This model was validated on patients from the other centres (detection rate 67%; false-positive rate 5.6%; AUROC=0·82). INTERPRETATION: Our data suggest that an immune response, reflected by TIL levels in the primary tumour, has an important role in the improved survival seen in most HPV-positive patients, and is relevant for the clinical evaluation of HPV-positive OPSCC.

Audit of the care of patients with epilepsy in general practice.

BACKGROUND: Previous studies have shown that there is great potential for improving the management of patients with epilepsy. AIM: To identify all patients with epilepsy, to evaluate and audit their care in relation to an annual review, to document seizure frequency and appropriateness of daily therapy to aid compliance and to propose strategies to improve these and other aspects of epileptic care. METHOD: An audit of the care of patients with epilepsy was undertaken in two King's Lynn practices with a combined population of 22,500. Principles for the management of epilepsy were established. From these principles, the following standards were agreed: 75% of patients on treatment for epilepsy should be seen every year, 75% of patients should have their seizure frequency documented, and 75% of patients should take their anti-epileptic drugs no more than twice daily. As a result of the first audit cycle, changes were made in the documentation and advice regarding treatment relating to these standards. RESULTS: The first audit cycle showed that 83% of patients had been seen at least once in the previous year, that documentation of seizure frequency existed for 51% of patients in the past year, and that 63% of patients were taking their treatment no more than twice daily. The evaluation was repeated 22 months later and an overall improvement was demonstrated in the first two results: 95% of patients had been seen in the past year, 93% had had their seizure frequency documented; however, only 66% of patients were taking their treatment twice daily or less. CONCLUSION: Call and recall, and documentation of seizure frequency were improved by this clinical audit. However, alterations in daily therapy appeared difficult for a variety of reasons; for example, therapy might have been initiated by a hospital specialist, and patients in a stable condition might have been apprehensive about changes. In order to improve the care of patients with epilepsy, a primary care team approach is desirable within a structure of good specialist services.