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/TILhigh=96%, HPV-positive/TILlow=59%). Survival of HPV-positive/TILlow 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

Habitat attributes of landscape mosaics along a gradient of matrix development intensity: Matrix management matters

The matrix is an important element of landscape mosaics that influences wildlife indirectly through its influence on habitat, and directly, if they live in ormove through it.Therefore, to quantify andmanage habitat quality for wildlife in modified landscapes, it is necessary to consider the characteristics of both patch and matrix elements of the whole landscape mosaic. To isolate matrix effects from the often simultaneous and confounding influence of patch and landscape characteristics, we identified nineteen 500 mradius landscapes in southeastQueensland, Australiawith similar remnant forest patch attributes, habitat loss, and fragmentation, but exhibiting a marked gradient from rural through high-density suburban development of the matrix, quantified by a weighted road-length metric. We measured habitat disturbance, structure, and floristics in patch core, patch edge andmatrix landscape elements to characterise how landscape habitat quality changes for small mammals. Correlation analyses identified that with increased matrix development intensity, human disturbance of core sites increased, predators and exotic plant species richness in matrix sites increased, and structural complexity (e.g. logs and stumps) in the matrix decreased. Ordination analyses showed landscape elements were most similar in habitat structure and floristics at low to moderate levels of matrix development, suggesting enhanced landscape habitat quality. Matrix development intensity was not, however, the greatest source of overall variation of habitat throughout landscapes. Many variables, such as landholder behaviour, complicate the relationship. For enhanced conservation outcomes the matrix needs to be managed to control disturbances and strategically plan for matrix habitat retention and restoration