ctDNA to Predict Treatment Response in Head and Neck Squamous Cell Carcinoma: A Systematic Review

To investigate the potential role of plasma circulating tumor DNA (ctDNA) in predicting treatment response in HPV-positive and HPV-negative Head and Neck Squamous Cell Carcinoma (HNSCC).

Medline, PubMed, Cochrane databases (Cochrane Library, Cochrane Central Register of Controlled Trials) and EMBASE databases were searched in accordance with the standard PICOTS model.

Search results were independently reviewed by two primary authors. Disagreements were adjudicated by the senior author. Studies were excluded according to defined exclusion criteria. Studies were assessed for quality in accordance with the REMARK guidelines. Data were then extracted, and findings were discussed narratively.

From a total of 1026 articles initially retrieved, 18 papers were included in the final review. Study quality was suboptimal, with a median REMARK score of 12.65/20. Short follow-up (median 24.5 months) and modest cohort sizes (median 59 patients) were observed. Most studies (13/18) investigated HPV ctDNA alone, and ctDNA detection methods varied considerably between studies. Broadly, studies showed that ctDNA monitoring has a high negative predictive value (91.7%) for residual and recurrent disease. Persistently positive ctDNA corresponded with poorer outcomes overall, but there was variability in the positive predictive value between studies, which was mitigated by consecutive testing.

These results suggest there is potential for ctDNA utility in surveillance for both HPV-positive and HPV-negative HNSCC patients; however, better adherence to reporting guidelines will enable meta-analysis.