Circulating HPV16 DNA may complement imaging assessment of early treatment efficacy in patients with HPV-positive oropharyngeal cancer

Abstract

Background: Early detection of treatment failure may improve clinical outcome and overall survival in patients with head and neck cancer after first-line treatment. Circulating cell-free HPV16 DNA (cfHPV16 DNA) was evaluated as a possible complementary marker to radiological assessment of early response in patients with HPV-related oropharyngeal cancer (OPC) after radiotherapy alone or combined with chemotherapy. Methods:The study included 66 patients with HPV-related OPC receiving radical radiotherapy alone or in combination with chemotherapy. cfHPV16 DNA was assessed in the blood of all patients before treatment using TaqManbased qPCR. Subsequent analysis of cfHPV16 DNA was performed 12 weeks after treatment completion, along with radiological assessment of early treatment results.Results: Complete (CRR) and incomplete radiological response (IRR) was found in 43 (65%) and 23 (35%) patients respectively. cfHPV16 DNA was present in 5 (28%) patients with IRR, while only in 1 (4%) with CRR. Three of five patients with IRR that were positive for cfHPV16 DNA exhibited histopathologically confirmed local or regional treatment failure, and other two developed distant metastases. None of the patients with negative cfHPV16 DNA presented disease failure. Conclusion:The post-treatment assessment of cfHPV16 DNA in patients with HPV-related OPC may be used as a complementary biomarker to conventional imaging-based examinations for early identification of treatment failure.

Utility of Plasma Circulating Tumor DNA and Tumor DNA Profiles in Head and Neck Squamous Cell Carcinoma

“…[34] In hereditary nonpolyposis colorectal cancer, HPV16 level in cfDNA after radical radiotherapy alone or in combination with chemotherapy had been suggested to be useful as a complementary biomarker for the early identi cation of treatment failure. [35] These results indicate that patient-speci c ctDNA analysis is a highly sensitive approach for surveillance of HNC, allowing early detection and the possibility of therapeutic intervention.…”

Longitudinal measurement of HPV copy number in cell-free DNA is associated with patient outcomes in HPV-positive oropharyngeal cancer

“…All 40 of these patients remained disease free. Previous studies of comparable size (22e67 cases studied longitudinally) have shown a similar percentage of patients (80e91%) who were cfDNA positive for HPV at presentation, who then became persistently cfDNA negative for HPV following treatment [23,25,27,30]. Of note, each of these studies have different assay methods, sampling timepoints and study endpoints.…”

“…In assessing association with treatment outcomes, Chera et al define a "favorable cfDNA clearance profile" based on pre-treatment HPV copy number and >95% clearance by week 4 of treatment [23]. Rutkowski used the 12-week posttreatment timepoint to define sensitivity and specificity for detecting treatment failure up to 6 months post-treatment [30]. Lee et al reported patient outcomes based on NGS-assayed HPV at 6 and 12 weeks post-treatment [27].…”

Utility of plasma circulating tumor DNA and tumor DNA profiles in head and neck squamous cell carcinoma

“…In the same study, ctDNA was not detected in plasma from 31 patients without recurrence 32 . In hereditary nonpolyposis colorectal cancer, HPV16 level in cfDNA after radical radiotherapy alone or in combination with chemotherapy had been suggested to be useful as a complementary biomarker for the early identification of treatment failure 33 . These results indicate that patient-specific ctDNA analysis is a highly sensitive approach for surveillance of HNC, allowing early detection and the possibility of therapeutic intervention.…”