美国人类乳头瘤病毒（HPV）感染最常引起的癌症是口咽癌(OPC)，自世纪之交以来其发病率不断上升。由于化疗和放疗具有长期明显不良反应，且HPV阳性OPC的良好预后，因此寻找适当的减弱治疗策略已成为头颈外科、放射肿瘤学和医学肿瘤学等学术领域过去十年的关键问题。然而，第一代减弱化疗随机试验未能改变标准治疗，引发了对减弱治疗可行性的担忧。国家数据库研究估计，多达三分之一的患者接受非标准的减弱治疗，其专科特殊性差异很大。综合多学科减弱治疗数据和当前治疗标准，对肿瘤学界来说是强化最佳实践和确保患者最佳结果的重要方面。在本综述中，作者总结和比较了前瞻性HPV阳性OPC减弱治疗试验的情况。减弱化疗会损害疗效但不降低毒性。有限的数据比较经口机器人手术（TORS）与放疗在毒性和疗效方面令人担忧。有令人兴奋的数据支持TORS后的辅助治疗减弱策略，但需要确定治疗指征的共识。有报道表明，促进放疗的减弱策略是可行的（前期剂量减少和诱导化疗基于患者的选择），但一级证据需要数年时间才能得出。最终，分期和HPV状态可能不足以指导减弱治疗。减弱治疗的未来可能在于结合治疗反应评估，充分利用个体化医学的力量和整合实时监测。© 2022作者。由Wiley Periodicals LLC代表美国癌症协会出版的《CA:医师癌症杂志》。

The most common cancer caused by human papillomavirus (HPV) infection in the United States is oropharyngeal cancer (OPC), and its incidence has been rising since the turn of the century. Because of substantial long-term morbidities with chemoradiation and the favorable prognosis of HPV-positive OPC, identifying the optimal deintensification strategy for this group has been a keystone of academic head-and-neck surgery, radiation oncology, and medical oncology for over the past decade. However, the first generation of randomized chemotherapy deintensification trials failed to change the standard of care, triggering concern over the feasibility of de-escalation. National database studies estimate that up to one third of patients receive nonstandard de-escalated treatments, which have subspecialty-specific nuances. A synthesis of the multidisciplinary deintensification data and current treatment standards is important for the oncology community to reinforce best practices and ensure optimal patient outcomes. In this review, the authors present a summary and comparison of prospective HPV-positive OPC de-escalation trials. Chemotherapy attenuation compromises outcomes without reducing toxicity. Limited data comparing transoral robotic surgery (TORS) with radiation raise concern over toxicity and outcomes with TORS. There are promising data to support de-escalating adjuvant therapy after TORS, but consensus on treatment indications is needed. Encouraging radiation deintensification strategies have been reported (upfront dose reduction and induction chemotherapy-based patient selection), but level I evidence is years away. Ultimately, stage and HPV status may be insufficient to guide de-escalation. The future of deintensification may lie in incorporating intratreatment response assessments to harness the powers of personalized medicine and integrate real-time surveillance.© 2022 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.