BACKGROUND: Extracapsular spread (ECS) is commonly used to justify adjuvant chemotherapy in patients with head and neck cancer. The role of ECS as a prognosticator and adjuvant therapy determinant in surgically resected, human papillomavirus-related oropharyngeal squamous cell carcinoma (OPSCC), however, has never been determined. METHODS: Of 210 oropharynx patients in a prospective transoral laser microsurgery database, 152 patients who had p16-positive primary OPSCC and pathologically positive necks were eligible for the study. ECS was measured from routine reporting (ECS report ) and by using a novel histologic grading system (ECS graded ). Proportional hazards models and matched analyses were used to compare the impact of ECS and adjuvant therapy on disease-free survival (DFS). Patients with and without graded ECS were matched for T-stage, surgical margins, and adjuvant therapy. RESULTS: At a median follow-up of 43 months, the presence of ECS was not associated with poorer DFS in multivariate analyses (ECS report : hazard ratio [HR], 3.42; 95% confidence interval [CI], 0.45-25.88; P ¼ .23; ECS graded : HR, 2.54; 95% CI, 0.88-7.34; P ¼ .09). T-stage and high-grade ECS, ie soft tissue metastasis (STM graded ) were prognostic. Overall and in the presence of ECS or even STM, adjuvant CRT was not associated with better DFS over radiotherapy alone (HR, 0.25; 95% CI, 0.06-1.13; P ¼ .07). In addition, matched analyses demonstrated no significant reduction in DFS for the presence of ECS versus the absence of ECS or reduced DFS for the administration of adjuvant radiotherapy alone versus CRT in ECS-positive patients. CONCLUSIONS: Routinely reported ECS was not prognostic in this study. Adjuvant CRT versus radiotherapy alone produced no improvement in DFS for ECS-positive patients. The authors propose that de-escalated adjuvant therapy should be considered for patients with p16-positive OPSCC who undergo surgery and that routinely reported ECS should not be used to justify adjuvant chemotherapy. Cancer 2012;118:3519-

We document a well-delineated set of prognostic variables that specifically and accurately identify individuals at risk of reduced outcomes in an otherwise good prognosis p16+ OPSCC cohort. Based on these prognosticators, appropriate patient counseling, adjuvant treatment recommendations, and stratification for trials can more accurately be made. We also observed an additional edge conferred by TLM toward more accurate clinical as well as pathological T staging.

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Objective With good loco-regional control, disease failure in p16-positive oropharyngeal squamous cell carcinoma (OPSCC) mainly results from distant metastasis (DM). Our objective was to characterize the patterns and clinical outcomes of DM in p16-positive OPSCC and compare these to patients with p16-negative disease. Methods Primary OPSCC patients who developed DM after completing surgical or non-surgical treatment were identified and p16 status was evaluated. Patterns of DM and post-DM progression-free (PFS) and disease-specific survival (DSS) were assessed. Results Forty-one of the 66 (62%) patients with DM were p16-positive. DM patterns were not statistically different by p16 status. However, p16-positive patients developed DM later in their course and had longer survival. All p16-negative patients either had progression or died within 24 months of DM detection whereas the 2-year post-DM PFS in the p16-positive group was 20% (95% CI:8–32.5%,p=0.003). The 3-year post-DM disease-specific survival (DSS) estimate in the p16-positive patients was 16% (95%CI: 7–18%) while all p16-negative patients died within 34 months (p<0.001). p16-negativity, loco-regional disease, and no/palliative versus curative intent treatment were all associated with reduced post-DM DSS in multivariate analysis. Conclusions The DM pattern did not differ remarkably between p16-positive and negative OPSCC patients in our practice. In p16-positive OPSCC with pulmonary oligometastatic disease, curative intent treatment and optimized locoregional control for the index primary prolonged survival.

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.