Purpose: Human papillomavirus-16 (HPV16) is the causative agent in a biologically distinct subset of oropharyngeal squamous cell carcinoma (OPSCC) with highly favorable prognosis. In clinical trials, HPV16 status is an essential inclusion or stratification parameter, highlighting the importance of accurate testing.Experimental Design: Fixed and fresh-frozen tissue from 108 OPSCC cases were subject to eight possible assay/assay combinations: p16 immunohistochemistry (p16 IHC); in situ hybridization for highrisk HPV (HR HPV ISH); quantitative PCR (qPCR) for both viral E6 RNA (RNA qPCR) and DNA (DNA qPCR); and combinations of the above.Results: HPV16-positive OPSCC presented in younger patients (mean 7.5 years younger, P ¼ 0.003) who smoked less than HPV-negative patients (P ¼ 0.007). The proportion of HPV16-positive cases increased from 15% to 57% (P ¼ 0.001) between 1988 and 2009. A combination of p16 IHC/DNA qPCR showed acceptable sensitivity (97%) and specificity (94%) compared with the RNA qPCR "gold standard", as well as being the best discriminator of favorable outcome (overall survival P ¼ 0.002). p16 IHC/HR HPV ISH also had acceptable specificity (90%) but the substantial reduction in its sensitivity (88%) impacted upon its prognostic value (P ¼ 0.02). p16 IHC, HR HPV ISH, or DNA qPCR was not sufficiently specific to recommend in clinical trials when used in isolation.Conclusions: Caution must be exercised in applying HPV16 diagnostic tests because of significant disparities in accuracy and prognostic value in previously published techniques.

Meta-analysis and comparative systematic review confirm that FNAC is highly effective in the diagnosis of head and neck masses, with some limitations.

Objective The rapid worldwide rise in incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has generated studies confirming this disease as an entity distinct from traditional OPSCC. Based on pathology, surgical studies have revealed prognosticators specific to HPV-positive OPSCC. The current AJCC/UICC staging and pathologic nodal (pN)-classification do not differentiate for survival, demonstrating the need for new, HPV-specific OPSCC staging. The objective of this study was to define a pathologic staging system specific to HPV-positive OPSCC. Methods Data were assembled from a surgically-managed, p16-positive OPSCC cohort (any T, any N, M0) of 704 patients from five cancer centers. Analysis was performed for a) the AJCC/UICC pathologic staging, b) newly published clinical staging for non-surgically managed HPV-positive OPSCC and c), a novel, pathology-based, “HPVpath” staging system that combines features of the primary tumor and nodal metastases. Results A combination of AJCC/UICC pT-classification and pathology-confirmed metastatic node count (<4 versus ≥5) yielded three groups, stages I (pT1-T2, ≤ 4 nodes), II (pT1-T2, ≥ 5 nodes; pT3-T4, ≤ 4 nodes), and III (pT3-T4, ≥ 5 nodes), with incrementally worse prognosis (Kaplan-Meier overall survival of 90%, 84% and 48% respectively). Existing AJCC/UICC pathologic staging lacked prognostic definition. Newly published HPV-specific clinical stagings from non-surgically managed patients, although prognostic, showed lower precision for this surgically managed cohort. Conclusions Three loco-regional “HPVpath” stages are identifiable for HPV-positive OPSCC, based on a combination of AJCC/UICC primary tumor pT-classification and metastatic node count. A workable, pathologic staging system is feasible to guide prognosis and adjuvant therapy decisions in surgically-managed HPV-positive OPSCC.