Plasma Circulating HPV DNA Surveillance in a Patient With Nasopharyngeal Cancer.

Siddharth Sheth,Tyler Walburn,Jason Tasoulas,Samip Patel,Ankit Agarwal,Margaret L Gulley
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Abstract

Nearly one third of nasopharyngeal carcinomas (NPCs) in the United States are associated with human papillomavirus (HPV). Surveillance for Epstein-Barr virus (EBV)-negative subtypes is customarily based solely on imaging and physical examinations. We present a case of HPV-positive NPC using serial circulating tumor HPV DNA (ctHPVDNA) as a biomarker of disease status. A 58-year-old Caucasian female initially presented with T1N1M0 EBV-negative p16-positive squamous cell carcinoma of the nasopharynx and was treated with concurrent chemoradiation. Regional nodal recurrence identified 7 months post-radiotherapy was treated with salvage left neck dissection. Surveillance was supplemented using a commercially available polymerase chain reaction (PCR)-based ctHPVDNA assay. Rising ctHPVDNA levels at 9 and 10 months post salvage surgery prompted positron emission tomography (PET). Biopsy confirmed recurrence in avid right hilar and paraoesophageal lymph nodes. Following definitive radiotherapy to the involved nodes and concurrent pembrolizumab, posttreatment ctHPVDNA decreased to baseline, but then increased after 6 cycles of pembrolizumab. Follow-up PET found left mediastinal recurrence outside of the prior treatment field, which was treated with concurrent chemoradiation with cetuximab. Again, ctHPVDNA level dropped to baseline but increased 3 months postradiation. PET scan showed a left lung nodule, and the patient received systemic therapy. Plasma ctHPVDNA monitoring correlated well with disease activity in our patient with HPV-positive NPC. ctHPVDNA detected disease earlier than standard surveillance methods and allowed for earlier intervention. Larger studies are needed to validate the utility of HPV biomarker surveillance in NPC.
对一名鼻咽癌患者进行血浆循环 HPV DNA 监测
在美国,近三分之一的鼻咽癌(NPC)与人类乳头瘤病毒(HPV)有关。对爱泼斯坦-巴氏病毒(EBV)阴性亚型的监测通常仅基于成像和体检。我们介绍了一例使用序列循环肿瘤 HPV DNA(ctHPVDNA)作为疾病状态生物标志物的 HPV 阳性鼻咽癌病例。一名 58 岁的白种女性最初患鼻咽 T1N1M0 EBV 阴性 p16 阳性鳞状细胞癌,接受了同期化疗。放疗后 7 个月发现区域性结节复发,患者接受了左颈部切除术进行挽救治疗。使用市售的基于聚合酶链反应(PCR)的ctHPVDNA检测法对患者进行监测。抢救性手术后 9 个月和 10 个月,ctHPVDNA 水平上升,促使进行正电子发射断层扫描(PET)。活检证实,右侧肺门和食管旁淋巴结复发。在对受累淋巴结进行确定性放疗并同时使用pembrolizumab后,治疗后ctHPVDNA降至基线,但在使用6个周期的pembrolizumab后又有所增加。随访 PET 发现左纵隔复发在先前的治疗区域之外,该患者同时接受了西妥昔单抗化疗。ctHPVDNA水平再次降至基线,但在放疗后3个月有所上升。PET 扫描显示左肺结节,患者接受了全身治疗。血浆ctHPVDNA监测结果与HPV阳性鼻咽癌患者的疾病活动性密切相关。需要进行更大规模的研究来验证 HPV 生物标记监测在鼻咽癌中的实用性。
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