This study aimed to evaluate the diagnostic and surveillance performance of circulating tumour human papillomavirus DNA for post-treatment monitoring of human papilloma virus–positive oropharyngeal squamous cell carcinoma.

Systematic review and meta-analysis of prospective studies (2019–2024) identified from PubMed, Web of Science and Scopus. Random-effects models were used to pool circulating tumour human papillomavirus DNA detectability and summarise lead-times to recurrence.

Fifteen studies (n=1,447) were included; 10 cohorts (n=731) entered the quantitative meta-analysis. Pooled baseline detectability was 85.5 per cent (95 per cent confidence interval 78.2–90.6). Circulating tumour human papillomavirus DNA positivity preceded clinical recurrence by a mean of 76.8 days (median 87.5). Specificity and negative predictive value were consistently high, whereas sensitivity varied by assay platform and sampling frequency.

Serial circulating tumour human papilloma virus DNA testing is a reliable adjunct to post-treatment surveillance in HPV-positive oropharyngeal squamous cell carcinoma, offering a clinically meaningful lead-time to recurrence. Standardised assays and multicentre validation are warranted.