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Head and Neck Surgery

(469) Synchronous Primaries Confound CtHPVDNA Monitoring: A Case Report

Monday, October 2, 2023
2:45 PM – 3:45 PM East Coast USA Time

    Presenting Author(s)

  • SN

    Saskia Naegele, MD

    Resident
    Northwell Health
    New York, New York, United States

    • Co-Author(s)

  • VE

    Vasileios Efthymiou, MD

    Department of Otolaryngology–Head and Neck Surgery, Massachusetts Eye and Ear, USA

  • DD

    Dipon Das, PhD

    Department of Otolaryngology–Head and Neck Surgery, Massachusetts Eye and Ear, USA

  • JM

    Julia Mendel, BS

    Department of Otolaryngology–Head and Neck Surgery, Massachusetts Eye and Ear, USA

  • AC

    Annie Chan, MD

    Department of Radiation Oncology, Massachusetts General Hospital, USA

  • Jeremy D. Richmon, MD

    Associate Professor of Otolaryngology-Head and Neck Surgery
    Department of Otolaryngology–Head and Neck Surgery, Massachusetts Eye and Ear
    Boston, Massachusetts, United States

    • Senior Author(s)

  • Daniel L. Faden, MD

    Assistant Professor
    Department of Otolaryngology–Head and Neck Surgery Harvard Medical School
    Boston, MA, United States

Disclosure(s):
Jeremy D. Richmon, MD: No relevant relationships to disclose.


Introduction: Human papillomavirus-associated head and neck squamous cell carcinoma (HPV+HNSCC) includes oropharyngeal SCC (HPV+OPSCC), sinonasal SCC (HPV+SNSCC), and nasopharyngeal carcinoma (HPV+NPC). Circulating tumor HPV DNA (ctHPVDNA) is detectable in the blood at diagnosis in most HPV+OPSCC patients, accurately tracks treatment response in real time, detects recurrence, and can be utilized with equal efficacy in HPV+ SNSCC and NPC. While the majority of HPV+HNSCC patients develop a single primary tumor, up to 7.4% develop synchronous or metachronous HPV+ primaries that are caused by the same viral isolate, which could confound ctHPVDNA monitoring. Here, we present a case and discuss the considerations of interpreting ctHPVDNA in the face of such a confounder.

Methods: A 65-year-old male who presented with T2N1M0 HPV16+OPSCC was enrolled in our prospective observational ctHPVDNA study. Blood was collected before transoral robotic surgery and neck dissection, on postoperative day 1 (POD 1), and before, during, and after adjuvant radiation therapy.

Results: The patient’s ctHPVDNA decreased on POD 1, but did not fully clear. At the end of adjuvant radiation therapy, ctHPVDNA had increased further. Biopsy of a sinonasal mass seen on follow-up MRI revealed HPV16+SNSCC. After endoscopic resection of the second HPV+ primary, ctHPVDNA cleared.

Conclusions: We report longitudinal monitoring of ctHPVDNA in a patient with multiple HPV+ primaries in which persistence of ctHPVDNA after surgery was, at least in part, due to the second untreated and unknown tumor, as opposed to residual disease from the known cancer. As the incidence of HPV+HNSCC continues to increase, and as deintensification with surgical treatment alone becomes more common, it is likely that the prevalence of multiple HPV+HNSCC will also increase. Thus, as ctHPVDNA monitoring becomes implemented into clinical practice, it is critical to recognize, and factor into confirmatory testing, that molecular detection of disease can come not only from the primary tumor or metastatic clones, but also synchronous or metachronous second primaries.