Predictive impact of human papillomavirus circulating tumor DNA in treatment response monitoring of HPV‐associated cancers; a meta‐analysis on recurrent event endpoints

BACKGROUND: HPV infection can cause cancer, and standard treatments often result in recurrence. The extent to which liquid biopsy using HPV circulating tumor DNA (HPV ctDNA) can be used as a promising marker for predicting recurrence in HPV‐related cancers remains to be validated. Here we conducted a systematic review and meta‐analysis to assess its effectiveness in predicting treatment response. METHODS: We conducted a systematic literature search of online databases, including PubMed, Embase, Scopus, and the Cochrane Library, up to December 2022. The goal was to identify survival studies that evaluated the potential of plasma HPV ctDNA at baseline and end‐of‐treatment (EoT) in predicting recurrence of related cancers. Hazard ratios were estimated directly from models or extracted from Kaplan–Meier plots. RESULTS: The pooled effect of HPV ctDNA presence on disease recurrence was estimated to be HR = 7.97 (95% CI: [3.74, 17.01]). Subgroup analysis showed that the risk of recurrence was HR = 2.17 (95% CI: [1.07, 4.41]) for baseline‐positive cases and HR = 13.21 (95% CI: [6.62, 26.36]) for EoT‐positive cases. Significant associations were also observed between recurrence of oropharyngeal squamous cell carcinoma (HR = 12.25 (95% CI: [2.62, 57.36])) and cervical cancer (HR = 4.60 (95% CI: [2.08, 10.17])) in plasma HPV ctDNA‐positive patients. CONCLUSIONS: The study found that HPV ctDNA detection can predict the rate of relapse or recurrence after treatment, with post‐treatment measurement being more effective than baseline assessment. HPV ctDNA could be used as a surrogate or incorporated with other methods for detecting residual disease.