Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Importance: Circulating tumor human papillomavirus (HPV) DNA (ctHPVDNA) is an important biomarker for the presence of HPV associated-oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) and is under investigation as a potential biomarker for treatment selection and disease surveillance. However, little is known about early postoperative kinetics related to tumor burden and ctHPVDNA clearance.
Objective: To investigate the post-operative kinetics of ctHPVDNA in surgically managed patients with HPV(+)OPSCC.
Design, setting and participants: Patients with newly diagnosed HPV(+)OPSCC undergoing surgical management were enrolled in this prospective biomarker trial (NCTN: NCT06356272). HPV status was defined as positive if p16 IHC and/or HPV DNA ISH and/or E6/E7 RNA ISH was positive. Patients had no history of prior head and neck cancer and were clinically M0. Blood was drawn prior to surgery (pretreatment), 1-2 days after surgery (POD1-2), and approximately 2 weeks after surgery (POW2) (range: 7-21 days). ctHPVDNA was quantified by NavDx (Tumor Tissue Modified Viral (TTMV)-HPV DNA, Naveris Inc.). Tumor size, lymph node size, and pretreatment TTMV-HPV DNA were included in a logistic regression model for the association with POD1-2 detectability. We additionally analyzed the concordance between ctHPVDNA results at POD1-2 and at POW2.
Results: Between October 20, 2015, and February 22, 2024, 92 patients were enrolled and underwent curative intent surgery. 66 (72%) had blood draws available pretreatment, 73 (79%) on POD1-2, and 61 (66%) at POW2. 47 (51%) patients had all time points available. 24 of 73 (33%) had detectable TTMV-HPV DNA at POD1-2, 4 of 61 (7%) had detectable TTMV-HPV DNA at POW2. Larger tumor (≥4 cm) and lymph node (≥4 cm) size were associated with POD1-2 detectability and the logistic regression model had an AUC of 0.73 (95%CI 0.59-0.87). Of the 22 patients with detectable TTMV-HPV DNA on POD1-2 and a POW2 blood draw, 19 (86%) were undetectable at POW2. Of the 34 patients with undetectable TTMV-HPV DNA at POD1-2 and a POW2 draw, only 1 (3%) patient converted to detectable. Progression free survival (PFS) for the overall cohort at 3 years was 94% (88-99%). Analyses for the association of post-operative TTMV-HPV DNA and PFS were not performed given few events.
Conclusions: Tumor size and lymph node size were associated with early postoperative TTMV-HPV DNA detectability. Patients with a ≥4 cm primary tumor and with a largest involved lymph node of ≥4 cm are estimated to have a 68% chance of POD1-2 ctHPVDNA positivity. In our cohort, 86% of patients with detectable TTMV-HPV DNA at POD1-2 converted to undetectable at POW2. Patients with early undetectable TTMV-HPV DNA are highly likely to remain undetectable at POW2 (97%). These data are useful to inform timepoint optimization for MRD.