HPV DNA in plasma and oral gargle from patients with HPV oropharyngeal cancer treated with radiation
MO-0871
Abstract
HPV DNA in plasma and oral gargle from patients with HPV oropharyngeal cancer treated with radiation
Authors: Michelle Echevarria1, Jimmy Caudell1, Youngchul Kim2, George Yang1, Sunil Kumar3, Charlotte Kuperwasser3, Catherine Del Vecchio Fitz3, Anna Giuliano4, Christine Chung5
1Moffitt Cancer Center, Radiation Oncology, Tampa, USA; 2Moffitt Cancer Center, Biostatistics and Bioinformatics, Tampa, USA; 3Naveris, Biotechnology, Waltham, USA; 4Moffitt Cancer Center, Cancer Epidemiology, Tampa, USA; 5Moffitt Cancer Center, Head and Neck, Tampa, USA
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Purpose or Objective
Changes in circulating tumor human papilloma virus (HPV) DNA and absence of detectable oral HPV DNA during and after treatment may be biomarkers of treatment response and recurrence. The goal of this study was to assess the kinetics of oral HPV DNA and tumor-derived plasma HPV DNA among HPV-positive oropharyngeal cancer (OPC) patients pre-, during, and post-radiotherapy (RT).
Material and Methods
Patients with T0-2 N0-1 p16-positive OPC were enrolled on a personalized definitive RT trial, with a total dose of 60-70 Gy. Plasma and oral gargle (OG) samples were collected prior to treatment, week 4 of treatment, at end of treatment (EOT), and 2-3 months, 6 months, and 12 months post-treatment. OG were additionally collected during weeks 1-3 of RT. HPV genotyping of OG cell DNA was performed utilizing the HPV SPF10 PCR-DEIA-LiPA25 line probe assay system. Circulating tumor HPV DNA was assessed in plasma using an assay that scores tumor tissue modified viral HPV DNA (TTMV) (Naveris, Natick, MA). Statistics were performed via Fisher’s exact test.
Results
OG HPV DNA was available in 48 patients, with 20 (43.8%) detectable pretreatment and 28 (64%) detectable prior to week 4. Patients with tonsil or soft palate primaries were more likely to have detectable OG HPV DNA compared with base of tongue/unknown primary (p=0.04). OG HPV DNA was cleared at week 4 in 27 of 31 (87.1%) who had a positive OG at any point prior to week 4, 28 of 35 (80%) at EOT, and 21 of 24 (87.5%) at 3 months. OG HPV DNA clearance at 4 weeks was not associated with a ≥ 32% volumetric CT imaging response at 4 weeks.
Pretreatment plasma TTMV was available in 48 patients and was detectable in 41 (82%), indeterminate in 2 (4%), and undetectable in 5 (10%). TTMV was detected more frequently in node positive patients (p=0.008) and never smokers (p=0.04). Of the 41 pretreatment TTMV positive patients, TTMV was undetectable in 16 of 41 patients (39%) at week 4, 27 of 39 (69.2%) at EOT, and 37 of 38 (97.4%) at 3 months. TTMV clearance at week 4 was associated with a ≥ 32% volumetric CT imaging response at 4 weeks (p=0.005).
During follow-up, two patients converted back to detectable TTMV at 6 and 12 months, respectively. Both patients were found to have a regional recurrence in the high dose volume and were salvaged. One additional pretreatment negative patient had a transient low-positive result at 3 months that subsequently resolved. This patient remains clinically and radiographically NED.
Conclusion
OG HPV, when detected, clears during RT in the majority of patients. TTMV clearance at week 4 is associated with a robust radiological response. Early clearance may be suggestive of radiosensitivity, and these patients may be candidates for aggressive de-escalation strategies. TTMV testing during surveillance may assist with monitoring, however further follow-up is needed.