Plasma Circulating HPV DNA Surveillance in a Patient With Nasopharyngeal Cancer

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.