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Purpose: Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) commonly affects people of working age, yet there is limited data regarding the return-to-work experience in this cohort. This study aimed to investigate the proportion of survivors currently working after completion of radiation therapy and to explore potential facilitators and barriers to working after treatment.Methods: A cross-sectional, single-institutional study was undertaken at the Peter MacCallum Cancer Centre, a comprehensive cancer center in Melbourne, Victoria, Australia. Eligible participants were 18 to 65 years old at diagnosis, were employed at or within the 3 months before diagnosis, and had completed curative treatment for HPV-associated OPC ≥4 months before enrollment. Participants completed a paper-based survey to assess baseline demographics, employment status, and quality of life (QOL; Functional Assessment of Cancer Therapy Head and Neck). Open-ended questions explored factors affecting return to work. Associations between current employment status and various disease, treatment, and demographic variables and with QOL were examined. Free-text items were analyzed by summarizing content analysis.Results: Of 93 participants approached, 68 responded (73.1%). Mean age was 54.1 years (range, 39-64 years), and 89.7% were male. Most participants (67.6%) had stage II disease and were treated with chemoradiation (85.3%). Mean time after treatment was 2.6 years (range, 0.3-9.1 years). Fifty-eight of 68 participants (85.3%) were working at enrollment; median time to return to work was 6.0 months (interquartile range, 4-10 months); 45 (77.6%) were in the same role and 35 (60.3%) worked the same number of hours. Ten participants were not working, 3 had retired, 5 reported persistent and significant treatment toxicity preventing employment. Survivors currently working reported higher physical, functional, and global QOL scores. Access to leave and support from treating doctors were facilitators for return to work, whereas fatigue was frequently reported as a barrier to returning to work.Conclusion: With time, the majority of participants with HPV-associated OPC will return to work after radiation therapy. Attention to symptom management and support from the workplace may enable more successful return to work. [ABSTRACT FROM AUTHOR]