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Background: Human papillomavirus (HPV)‐driven oropharyngeal squamous cell carcinomas (OPSCCs) demonstrate superior outcome compared with HPV‐negative OPSCCs. The eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, lymph node, metastasis (TNM) classification (TNM 2017) modifies OPSCC staging based on p16 positivity as a surrogate for HPV‐driven disease. In p16‐negative OPSCCs, lymph node (N) categories include extracapsular/extranodal extension (ECE); and, in p16‐positive OPSCCs, N categories are based on the number of positive neck lymph nodes omitting ECE status. The objective of the current study was to assess the prognostic impact of positive ECE status and the detection of HPV16 DNA in patients with p16‐positive OPSCC. Methods: In a cohort of 92 patients with p16‐positive, lymph node (N)‐positive (stage III‐IVB) OPSCC who underwent surgery and neck dissection, allowing for a pathologic examination of positive lymph nodes, 66 of 92 patients (71.4%) were p16‐positive/HPV16 DNA‐positive, 62 of 92 (67%) were ECE‐positive, and 45 of 62 (72.6%) were ECE‐positive, p16‐positive, and HPV16 DNA‐positive. Differences in outcome were assessed using Kaplan‐Meier plots and Cox proportional hazard regression (CoxR) for tumor‐specific survival and overall survival (OS). Results: The mean numbers of positive lymph nodes in ECE‐positive patients (5.0 positive lymph nodes; 95% CI, 3.8‐6.4 positive lymph nodes) and ECE‐negative patients (2.4 positive lymph nodes; 95% CI, 1.8‐2.9 positive lymph nodes) were different (P =.0007). ECE affected OS and tumor‐specific survival in p16‐positive patients (P =.007 and P =.047, respectively) and in p16‐positive/HPV16 DNA‐positive patients (P =.013 and P =.026, respectively). Related to the unequal distributions of ECE‐positive/HPV16 DNA‐negative tumors, the TNM 2017 failed to discriminate OS in patients with UICC stage I, II, and III disease (mean OS, 54.5, 73.4, and 45 months, respectively; median OS, 64.7 months, not reached, and 41.1 months, respectively). According to a univariate CoxR, the presence of ECE predicted impaired OS in patients with p16‐positive OPSCC (hazard ratio, 3.40; 95% CI, 1.17‐9.89; P =.025) and even greater impaired OS in those with p16‐positive/HPV16 DNA‐positive OPSCC (HR, 8.64; 95% CI, 1.12‐66.40; P =.038). Multivariate CoxR confirmed ECE and HPV16 DNA detection as independent predictors. Conclusions: ECE and HPV16 DNA status should be included in the prognostic staging of patients with p16‐positive OPSCC because several lines of evidence demonstrate their impact on survival. In a consecutive sample of 92 patients with p16‐positive oropharyngeal squamous cell carcinoma who underwent surgery with or without adjuvant radiotherapy/chemotherapy, extracapsular extension of neck lymph nodes and the absence of detectable human papillomavirus (HPV) subtype 16 DNA are linked to impaired outcomes. The staging of these patients should not omit but, rather, should include an assessment of HPV type 16 DNA and extracapsular extension because both are independent prognostic factors for overall survival and other outcome measures. [ABSTRACT FROM AUTHOR]

Background: Accurate, individualized prognostication in patients with oropharyngeal squamous cell carcinoma (OPSCC) is vital for patient counseling and treatment decision making. With the emergence of human papillomavirus (HPV) as an important biomarker in OPSCC, calculators incorporating this variable have been developed. However, it is critical to characterize their accuracy prior to implementation.Methods: Four OPSCC calculators were identified that integrate HPV into their estimation of 5-year overall survival. Treatment outcomes for 856 patients with OPSCC who were evaluated at a single institution from 2003 through 2016 were analyzed. Predicted survival probabilities were generated for each patient using each calculator. Calculator performance was assessed and compared using Kaplan-Meier plots, receiver operating characteristic curves, concordance statistics, and calibration plots.Results: Correlation between pairs of calculators varied, with coefficients ranging from 0.63 to 0.90. Only 3 of 6 pairs of calculators yielded predictions within 10% of each other for at least 50% of patients. Kaplan-Meier curves of calculator-defined risk groups demonstrated reasonable stratification. Areas under the receiver operating characteristic curve ranged from 0.74 to 0.80, and concordance statistics ranged from 0.71 to 0.78. Each calculator demonstrated superior discriminatory ability compared with clinical staging according to the seventh and eighth editions of the American Joint Committee on Cancer staging manual. Among models, the Denmark calculator was found to be best calibrated to observed outcomes.Conclusions: Existing calculators exhibited reasonable estimation of survival in patients with OPSCC, but there was considerable variability in predictions for individual patients, which limits the clinical usefulness of these calculators. Given the increasing role of personalized treatment in patients with OPSCC, further work is needed to improve accuracy and precision, possibly through the identification and incorporation of additional biomarkers. [ABSTRACT FROM AUTHOR]

Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing among older adults. It is unknown whether these trends can be explained by human papillomavirus (HPV) and whether HPV-related tumors remain associated with an improved prognosis among older patients.Methods: In a retrospective study of OPSCCs diagnosed from 1995 to 2013 at 2 National Comprehensive Cancer Network-designated cancer centers, p16 immunohistochemistry and in situ hybridization (ISH) for HPV-16, high-risk DNA, and/or E6/E7 RNA were performed. The median age at diagnosis was compared by p16 and ISH tumor status. Trends in age were analyzed with nonparametric trends. Survival was analyzed with the Kaplan-Meier method and Cox proportional hazards models.Results: Among 239 patients, 144 (60%) were p16-positive. During 1998-2013, the median age increased among p16-positive patients (Ptrend = .01) but not among p16-negative patients (Ptrend = .71). The median age of p16-positive patients increased from 53 years (interquartile range [IQR] in 1995-2000, 45-65 years) to 58 years (IQR for 2001-2013, 53-64 years). Among patients ≥ 65 years old, the proportion of OPSCCs that were p16-positive increased from 41% during 1995-2000 to 75% during 2007-2013 (Ptrend = .04). Among all age groups, including older patients, a p16-positive tumor status conferred improved overall survival in comparison with a p16-negative status.Conclusions: The median age at diagnosis for HPV-related OPSCC is increasing as the proportion of OPSCCs caused by HPV rises among older adults. The favorable survival conferred by an HPV-positive tumor status persists in older adults. Cancer 2018;124:2993-9. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]