Cell‐free human papillomavirus DNA kinetics after surgery for human papillomavirus–associated oropharyngeal cancer

Abstract

BACKGROUND: New ultrasensitive methods for detecting residual disease after surgery are needed in human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC). METHODS: To determine whether the clearance kinetics of circulating tumor human papillomavirus DNA (ctHPVDNA) is associated with postoperative disease status, a prospective observational study was conducted in 33 patients with HPV+OPSCC undergoing surgery. Blood was collected before surgery, postoperative days 1 (POD 1), 7, and 30 and with follow-up. A subcohort of 12 patients underwent frequent blood collections in the first 24 hours after surgery to define early clearance kinetics. Plasma was run on custom droplet digital polymerase chain reaction (ddPCR) assays for HPV genotypes 16, 18, 33, 35, and 45. RESULTS: In patients without pathologic risk factors for recurrence who were observed after surgery, ctHPVDNA rapidly decreased to <1 copy/mL by POD 1 (n = 8/8). In patients with risk factors for macroscopic residual disease, ctHPVDNA was markedly elevated on POD 1 (>350 copies/mL) and remained elevated until adjuvant treatment (n = 3/3). Patients with intermediate POD 1 ctH-PVDNA levels (1.2-58.4 copies/mL) all possessed pathologic risk factors for microscopic residual disease (n = 9/9). POD 1 ctHPVDNA levels were higher in patients with known adverse pathologic risk factors such as extranodal extension >1 mm (P = .0481) and with increasing lymph nodes involved (P = .0453) and were further associated with adjuvant treatment received (P = .0076). One of 33 patients had a recurrence that was detected by ctHPVDNA 2 months earlier than clinical detection. CONCLUSIONS: POD 1 ctHPVDNA levels are associated with the risk of residual disease in patients with HPV+OPSCC undergoing curative intent surgery and thus could be used as a personalized biomarker for selecting adjuvant treatment in the future.

Circulating tumor DNA in head and neck cancer: Early successes and future promise

“…The convergence of these studies demonstrates the potential of ctHPVDNA as a useful tool for predicting treatment response. Additionally, as evidenced by the patient identified with distant metastasis in O’Boyle et al's study, 8 bloodborne markers have potential advantages over salivary markers for the detection of regional and distant metastasis. Defining the optimal role for ctHPVDNA in managing oropharyngeal squamous cell carcinoma (OPSCC) will take robust prospective study, but it does have potential for describing the risk of recurrence, informing adjuvant therapy, and dictating appropriate surveillance.…”

“…In this issue of Cancer , O’Boyle et al 8 report leveraging ctHPVDNA for surveillance after transoral robotic surgery. The authors used digital droplet polymerase chain reaction to detect ctHPVDNA in 34 patients before and after transoral robotic surgery, and they suggest that levels of ctHPVDNA on postoperative day 1 (POD1) were significantly associated with pathologic risk for residual disease and traditional indications for adjuvant therapy.…”

“…O’Boyle et al's work 8 serves as a proof of concept for the feasibility of ctHPVDNA for detecting recurrence, but there are notable limitations. The primary limitations include a small cohort size with limited follow‐up duration for detecting recurrence.…”

“…1,2 Human papillomavirus-associated OPC provides a particularly exciting avenue for this research because both ctDNA and circulating tumor human papillomavirus DNA (ctHPVDNA) can be detected in the blood and saliva, [3][4][5][6] and this potentially could enable noninvasive genotyping and posttreatment surveillance. 2,7 In this issue of Cancer, O'Boyle et al 8 report leveraging ctHPVDNA for surveillance after transoral robotic surgery. The authors used digital droplet polymerase chain reaction to detect ctHPVDNA in 34 patients before and after transoral robotic surgery, and they suggest that levels of ctHPVDNA on postoperative day 1 (POD1) were significantly associated with pathologic risk for residual disease and traditional indications for adjuvant therapy.…”

“…15 ctDNA can also be used to evaluate for emerging resistance mechanisms to guide systemic treatment. 16,17 Although the focus of O'Boyle et al 8 is understanding patterns of ctHPVDNA after surgery, there is significant interest in using both ctDNA and ctHPVDNA for the initial diagnosis and screening of patients at high risk for OPC. Patients with early-stage disease generally have an excellent prognosis 18,19 ; unfortunately, early symptoms of OPC can be confused with common benign disorders and can cause delays in diagnosis.…”