While 32% of tested patients declined surgery based on a benign AGEC, 86% of patients with suspicious AGEC findings had unnecessary surgery, reflecting a substantially lower rate of malignancy from what was previously reported for all indeterminate nodules. Given the approximate pretest malignancy risk of 25-35% for an FNA diagnosis of SHCN or AFHCN, a suspicious AGEC diagnosis does not increase the probability of malignancy in an HCN, and patients should be counseled accordingly.

A critical aim of vaccine-related research is to identify the mechanisms by which memory T cells are formed and maintained over long periods of time. In recent years, we have designed experiments aimed at addressing two key questions: (i) what are the factors that maintain functionally responsive CD8+ memory cells over long periods of time, and (ii) what are the signals during the early stages of infection that drive the differentiation of long-lived CD8+ memory T cells? We have identified a role for CD4+ T cells in the generation of CD8+ T-cell-mediated protection from secondary challenge. While CD4+ T cells appear to play a role in the programme of CD8 memory, we find that they are also required for the long-term maintenance of CD8+ memory T-cell numbers and function. This property is independent of CD40-CD40L interactions, and we propose a role for CD4+ T cells in maintaining the ability of CD8+ memory T cells to respond to interleukin-7 (IL-7) and IL-15. By manipulating both the time course of infection and the timing of antigen presentation to newly recruited CD8+ T cells, we also demonstrate that the programming of effector and memory potential are at least partially distinct processes.

Objectives: The importance of detecting human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has resulted in a growing expectation for HPV testing of clinical samples. Although testing protocols vary, most pertain to primary tumor biopsies/resections. Testing of fine-needle aspirates and core biopsies (FNACBs) is advantageous, but it is unclear whether technical and biological factors adversely affect the fidelity of HPV detection in these samples. Methods: Data was collected for 85 patients with regionally metastatic HNSCC that had undergone FNACB with HPV analysis as part of clinical care. HPV testing consisted of p16 immunostaining and HPV in situ hybridization (ISH). The FNACBs were compared with the subsequent biopsies/resections for HPV status. Results: p16 staining was present in 60 cases (71%). p16 positivity was predictive of oropharyngeal origin (p < 0.001) and correlated with the presence of HPV by ISH (98% correlation). On comparison of the metastases and primary cancers, the HPV status was concordant in 58 of 59 cases (98%). Conclusions: For patients with metastatic HNSCC, p16 staining reliably reflects the HPV status of the primary tumor. p16 staining of FNACBs may obviate the need for more invasive sampling of the primary cancer solely for the purpose of HPV testing.

Confirmation of human papillomavirus (HPV) as a causative agent for a subset of biologically and clinically distinct squamous cell carcinomas of the head and neck (HNSCC) has resulted in a growing need and expectation for HPV testing of head and neck cancers. At the same time, opportunities to obtain tissue samples for HPV testing are diminishing: The sensitivity of HPV-related HNSCC to chemotherapy and ionizing radiation has limited the role of surgical resection, and diagnostic tissue biopsies/resections may not be available in a substantial portion of patients with small or occult primaries. Into this quandary steps the cytopathologist. Fine needle aspirates of metastatic HNSCCs and brushes of oropharyngeal cancers provide a valuable substrate for HPV analysis. These cytologic specimens are suitable for standard tissue-based methods of HPV detection such as immunoperoxidase and in situ hybridization, but the expanding demands for biomarker analysis of these limited samples is driving the development of alternative assays that eliminate the requirement for high cellularity and complex specimen processing. Various liquid phase assays already in widespread use for HPV analysis of cervical cancer risk may be directly transferrable to the head and neck context. Implementation of these assays may abrogate the current need for tissue acquisition of HNSCCs via a more aggressive surgical procedure.