Post-treatment monitoring of surgically treated oropharyngeal squamous cell carcinoma patients using human papillomavirus cell-free DNA.

INTRODUCTION: The incidence rate of human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) is increasing. Despite good prognosis, recurrence can decrease health-related quality of life and increase mortality, so post-treatment monitoring is important for patient outcomes. One potential biomarker for post-treatment monitoring is HPV cell-free DNA (cfDNA) from blood plasma. METHODS: Plasma samples at start of treatment and during follow-up from 27 OPSCC patients were analyzed for cfDNA of six high-risk HPV types using a multiplex digital PCR assay. Presence of HPV cfDNA was compared to HPV tumor status determined by p16(INK4a) immunohistochemistry, HPV DNA, HPV RNA and HPV16 E6 serology. RESULTS: At start of treatment, sensitivity of HPV cfDNA detection in HPV-driven OPSCC cases was 89 % (17/19), while specificity was 100 % among 39 plasma samples from 8 HPV-negative OPSCC cases. A median of 4 follow-up plasma samples per patient over a mean time of 11 months were available. Positive and negative predictive values during follow-up were assessed on a per-test-basis. HPV cfDNA testing after completion of therapy had a positive predictive value of 100 % for HPV-OPSCC recurrence within one year, and a negative predictive value of 98 %. In cases of recurrent HPV-driven OPSCC, HPV cfDNA was detectable between 3 and 6.8 months before detection of recurrence by routine follow-up examination methods. CONCLUSION: Post-treatment monitoring for early detection of recurrence could be aided by testing for HPV cfDNA in HPV-driven OPSCC patients.