Specificity and Sensitivity of Circulating Tumor HPV-DNA in Patients with HPV-Positive Oropharyngeal Squamous Cell Carcinoma.

The global incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing, mainly due to a rise in human papillomavirus-positive (HPV+) cases. In Denmark, this group now constitutes more than 70% of newly diagnosed patients with OPSCC, making HPV+ OPSCC an increasing health issue. Approximately 10-15% of patients experience recurrence after treatment, and 30% die within five years of diagnosis. Detecting recurrence can be challenging, as it relies on either visible findings during clinical examination or symptoms reported by the patient. However, recent studies have shown that circulating tumor HPV-DNA (ctHPV-DNA) is a promising biomarker for detecting recurrence. The aim of the study presented in this protocol is to investigate whether prospective and systematic ctHPV-DNA testing can improve the standard follow-up program by detecting recurrence earlier than, or simultaneously with, clinical or radiological examination. This study is a prospective diagnostic accuracy study aiming to include 200 newly diagnosed patients with HPV+ OPSCC. Patients will be followed systematically with blood samples at baseline before treatment initiation and at every standard follow-up visit after treatment completion for up to three years. If a sample after treatment completion is positive for ctHPV-DNA, the patient will be referred for clinical ENT examination and a PET/CT scan to assess if the patient has detectable recurrence. This study will provide novel knowledge of the sensitivity and specificity of ctHPV-DNA testing for detecting recurrence in patients with HPV+ OPSCC, based on a large, prospectively and systematically followed cohort in which positive ctHPV-DNA findings will be acted upon clinically.