Detection of Plasma Circulating Tumor-Tissue Modified HPV DNA Following Trans-Oral Robotic Surgery (TORS) and Neck Dissection for p16+ Oropharyngeal Squamous Cell Carcinoma

Abstract

This study sought to measure circulating plasma tumor-tissue modified human papilloma virus DNA (TTMV-HPV DNA) and kinetics following trans-oral robotic surgery (TORS), neck dissection, and adjuvant (chemo)radiation for p16+ oropharyngeal squamous cell carcinoma (OPSCC).Patients with p16+ OPSCC currently enrolled on an ongoing phase II clinical trial investigating radiation dose de-intensification following TORS and neck dissection (TORS version 2.0, NCT03729518) with available post-operative plasma samples were included. Plasma was collected following TORS procedure (∼6 weeks post-operatively), during adjuvant (chemo)radiation, and at treatment completion. Plasma samples were analyzed for TTMV-HPV DNA using a liquid biopsy assay. Multivariate robust linear regression analysis was used to identify clinicopathologic features associated with detectable post-operative TTMV-HPV DNA levels.Thirty-four patients were included (median age 59 years, IQR 55-62 years; 94% male). The majority of patients had pT1-2 (n = 32, 94%; 1 pT0,1 pT3) and pN1 (n = 32, 94%; 2 pN0) disease. Other pathologic features included LVI (n = 5, 15%), PNI (n = 2, 6%), close or positive margin (n = 9, 26%), number of positive nodes (median 1.5, IQR 1-2), largest node size (median 3.7 cm, IQR 3.0-4.4 cm), and ENE (n = 8, 24%; 4 macroscopic). The majority of patients had undetectable TTMV-HPV DNA following TORS (n = 31, 91%). Three patients (9%) had detectable TTMV-HPV DNA post-operatively with 2 having very low detectable levels (≤ 10 copies/mL) and 1 having a high detectable level (4421 copies/mL). Largest node size (P = 0.0083) and ENE (P = 0.041) were significantly associated with detectable post-operative TTMV-HPV DNA levels. Of those with initially undetectable TTMV-HPV DNA, levels remained undetectable during and after adjuvant (chemo)radiation with 1 patient developing a very low detectable level (7 copies/mL) following treatment. The 2 patients with low detectable TTMV-HPV DNA levels post-operatively (≤ 10 copies/mL) had complete clearance following adjuvant therapy. There were no locoregional recurrences (median follow-up 15 months, IQR 12-21 months) including the patient who developed a low detectable level (7 copies/mL) following treatment (currently 24 months post-TORS). The patient with the high detectable level post-operatively (4421 copies/mL) developed osseous metastatic disease 5 months post-TORS.Tumor-tissue modified HPV DNA can be detected with high sensitivity following definitive surgery for p16+ OPSCC. Further prospective studies are warranted to determine if the observed range of post-operative values allows for stratification of patients into those with distant metastatic disease, persistent locoregional disease that warrants adjuvant therapy, versus active surveillance.