Objective For human papillomavirus–associated oropharynx carcinoma treated with definitive surgery, we aimed to find predictors of adverse histopathology indicating the possible need for adjuvant therapy. Study Design Retrospective review. Setting National Cancer Database. Methods We analyzed 2347 eligible patients from 2010 to 2015. We evaluated (1) the ability of clinical nodal staging and extranodal extension designation per the AJCC, seventh edition (American Joint Committee on Cancer), to predict histopathology and (2) the likelihoods for adverse postsurgery histopathology by common clinical stages. Results Clinical nodal staging predicted pathologic nodal staging 65% of the time, with 24% (569/2347) being upstaged and 11% (251/2347) being downstaged. In patients with cN+ disease, clinical extranodal extension distinction had the following accuracy for pathologic extranodal extension: positive predictive value, 81% (88/109); negative predictive value, 73.1% (505/691); sensitivity, 32.1% (88/274); and specificity, 96.0% (505/526). Patients with cT1-2, N0-N2c, without clinical extranodal extension had the following proportions of pN2+ without pathologic extranodal extension (indicating consideration for adjuvant radiation): cN0, 11%; cN1, 31%; cN2a, 67% (8% downstaged); cN2b, 66% (6% downstaged); and cN2c, 35% (17% downstaged). From this group, patients had the following proportions of pathologic extranodal extension (indicating consideration for adjuvant chemoradiation): cN0, 6%; cN1, 20%; cN2a, 27%; cN2b, 28%; and cN2c, 48%. Conclusion For human papillomavirus–associated oropharynx carcinoma, nodal clinical staging per the American Joint Committee on Cancer, seventh edition, predicts pathologic stage about two-thirds of the time, leading to up- and downstaging. Clinical extranodal extension assessment has low sensitivity and moderate predictive capability. With careful selection, definitive surgery can allow patients to often avoid adjuvant chemotherapy and sometimes avoid adjuvant radiation.