Chau Nicole G, Rabinowits Guilherme, Haddad Robert I
Center for Head and Neck Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA,
Curr Treat Options Oncol. 2014 Dec;15(4):595-610. doi: 10.1007/s11864-014-0309-1.
Human papillomavirus-associated oropharynx cancer (HPV-OPC) is growing in incidence and has distinct clinical, pathologic, molecular, and epidemiologic features. However, the management of HPV-OPC does not presently differ from HPV-negative OPC based on the current evidence and requires complex multidisciplinary approaches. The superior prognosis of HPV-OPC and the toxicities of current multimodality treatment in a young population serve as the impetus to evaluate de-intensification treatment regimens aimed at reducing toxicity while maintaining therapeutic efficacy. Clinical trials are underway to evaluate reduced doses of radiation or less toxic systemic therapy regimens in HPV-OPC. Minimally invasive surgical approaches in the HPV-OPC population with early tumor stage also are being investigated. De-intensification strategies should only be employed in the context of clinical trials, and HPV-OPC patients should be offered clinical trials' participation. Appropriate patient selection is critical to the development of de-intensification regimens, and this requires greater understanding of risk factors within the HPV-OPC population, HPV-OPC biology, and how HPV modulates response to specific therapies. Smoking history and bulky nodal disease have been shown to impact negatively the favorable prognosis of HPV association. Validated biomarkers within the HPV-OPC population are lacking, although alterations in the PI3K pathway and markers of immune response may emerge as important considerations in the future. Novel therapeutic strategies are desperately needed particularly for HPV-OPC patients who fail definitive therapy, and select patients with recurrent or metastatic disease may benefit from aggressive approaches.
人乳头瘤病毒相关的口咽癌(HPV-OPC)发病率正在上升,具有独特的临床、病理、分子和流行病学特征。然而,根据目前的证据,HPV-OPC的治疗目前与HPV阴性的口咽癌并无差异,且需要复杂的多学科方法。HPV-OPC的预后较好,以及当前多模式治疗对年轻人群的毒性,促使人们评估旨在降低毒性同时维持治疗效果的降阶梯治疗方案。目前正在进行临床试验,以评估HPV-OPC中降低放疗剂量或毒性较小的全身治疗方案。对于肿瘤分期较早的HPV-OPC人群,微创外科手术方法也在研究之中。降阶梯策略应仅在临床试验的背景下采用,并且应向HPV-OPC患者提供参与临床试验的机会。合适的患者选择对于降阶梯方案的制定至关重要,这需要对HPV-OPC人群中的风险因素、HPV-OPC生物学以及HPV如何调节对特定治疗的反应有更深入的了解。吸烟史和巨大淋巴结疾病已被证明会对HPV相关性的良好预后产生负面影响。HPV-OPC人群中缺乏经过验证的生物标志物,尽管PI3K途径的改变和免疫反应标志物未来可能成为重要的考虑因素。尤其对于确定性治疗失败的HPV-OPC患者,迫切需要新的治疗策略,部分复发或转移性疾病患者可能从积极的治疗方法中获益。