880P - ctHPV16-DNA in Liquid Biopsy: A promising biomarker to monitor disease status in patients with HPV-positive oropharyngeal squamous cell carcinoma

Background

Globally the incidences of oropharyngeal squamous cell carcinoma (OPSCC), especially those associated with high-risk human papillomavirus are rising. Although patients with HPV-positive OPSCC present with better survival, up to 25% develop recurrent disease. Biomarkers to monitor therapy response, minimal residual disease and tumor burden during follow-up are urgently needed. The detection of cell-free (cf)HPV-DNA in blood plasma offers the opportunity for minimally invasive disease monitoring and early recurrence detection.

Methods

We examined 34 patients with HPV-related OPSCC and 21 controls (healthy donors and HPV-negative OPSCC patients) to investigate cfHPV16-DNA status prior to and during therapy as well as throughout follow-up. qPCR and ddPCR were applied to quantify the concentration of cfHPV16-DNA in plasma, using the viral gene E6 as a target.

Results

No cfHPV16-DNA or <10 copies per ml plasma were detected in healthy donors or HPV-negative OPSCC patients. Plasma samples from patients with HPV-positive OPSCC collected prior to treatment. At the cut-off of 10 copies/ml plasma, ddPCR showed 79% sensitivity, 80% specificity, 70% NPV, and 90% PPV, whereas qPCR showed 73% sensitivity, 80% specificity, 60% NPV, 90% PPV. Patients without clinical evidence of recurrence had significantly lower cfHPV16-DNA concentrations after therapy, whereas increase of copy number was correlated to recurrent disease.

Conclusions

Our results demonstrate that ddPCR is a more sensitive method compared to qPCR for detection of cfHPV16-DNA in plasma of patients with HPV16-positive OPSCC. cfHPV16-DNA correlated with tumor burden and therefore presents a promising diagnostic tool. Nevertheless, prospective studies with expanded patient cohorts are necessary to investigate the kinetics of cfHPV16-DNA in relation to therapy response and the development of recurrent and metastatic disease.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Dr. Nora Würdemann.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.