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PURPOSE Definitive or postoperative chemoradiation (CRT) is curative for human papillomavirus–associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a deintensification strategy, we studied primary transoral surgery (TOS) and reduced postoperative radiation therapy (RT) in intermediate-risk HPV+ OPC. METHODS E3311 is a phase II randomized trial of reduced- or standard-dose postoperative RT for resected stage III-IVa (American Joint Committee on Cancer-seventh edition) HPV+ OPC, determined by pathologic parameters. Primary goals were feasibility of prospective multi-institutional study of TOS for HPV+ OPC, and oncologic efficacy (2-year progression-free survival) of TOS and adjuvant therapy in intermediate-risk patients after resection. TOS plus 50 Gy was considered promising if the lower limit of the exact 90% binomial confidence intervals exceeded 85%. Quality of life and swallowing were measured by functional assessment of cancer therapy-head and neck and MD Anderson Dysphagia Index. RESULTS Credentialed surgeons performed TOS for 495 patients. Eligible and treated patients were assigned as follows: arm A (low risk, n = 38) enrolled 11%, intermediate risk arms B (50 Gy, n = 100) or C (60 Gy, n = 108) randomly allocated 58%, and arm D (high risk, n = 113) enrolled 31%. With a median 35.2-month follow-up for 359 evaluable (eligible and treated) patients, 2-year progression-free survival Kaplan-Meier estimate is 96.9% (90% CI, 91.9 to 100) for arm A (observation), 94.9% (90% CI, 91.3 to 98.6]) for arm B (50 Gy), 96.0% (90% CI, 92.8 to 99.3) for arm C (60 Gy), and 90.7% (90% CI, 86.2 to 95.4) for arm D (66 Gy plus weekly cisplatin). Treatment arm distribution and oncologic outcome for ineligible or step 2 untreated patients (n = 136) mirrored the 359 evaluable patients. Exploratory comparison of functional assessment of cancer therapy-head and neck total scores between arms B and C is presented. CONCLUSION Primary TOS and reduced postoperative RT result in outstanding oncologic outcome and favorable functional outcomes in intermediate-risk HPV+ OPC.

Background No reports describe falsepositive reverse transcriptase polymerase chain reaction (RT‐PCR) for novel coronavirus in preoperative screening. Methods Preoperative patients had one or two nasopharyngeal swabs, depending on low or high risk of viral transmission. Positive tests were repeated. Results Forty‐three of 52 patients required two or more preoperative tests. Four (9.3%) had discrepant results (positive/negative). One of these left the coronavirus disease (COVID) unit against medical advice despite an orbital abscess, with unknown true disease status. The remaining 3 of 42 (7.1%) had negative repeat RT‐PCR. Although ultimately considered falsepositives, one was sent to a COVID unit postoperatively and two had urgent surgery delayed. Assuming negative repeat RT‐PCR, clear chest imaging, and lack of subsequent symptoms represent the “gold standard,” RT‐PCR specificity was 0.97. Conclusions If false positives are suspected, we recommend computed tomography (CT) of the chest and repeat RT‐PCR. Validated serum immunoglobulin testing may ultimately prove useful.