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 p16INK4a 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.