The clinical utility of circulating human papillomavirus across squamous cell carcinomas.

Background and purpose: The similarities in biology, treatment regimens and outcome between the different human papillomavirus (HPV) associated squamous cell carcinomas (SCCs) allow for extrapolation of results generated from one SC tumor type to another. In HPV associated cancers, HPV is integrated into the tumor genome and can consequently be detected in the circulating fragments of the tumor DNA. Thus, measurement of HPV in the plasma is a surrogate for circulating tumor DNA (ctDNA) and holds promise as a clinically relevant biomarker in HPV associated cancers. With the present overview we aim to present the status of circulating HPV studies in SCCs, the clinical potential and the gaps of knowledge, with the overall aim to facilitate the next steps into clinically relevant prospective trials.

Material and methods: We reviewed the literature and presented the data for each tumor type as well as analyses of the clinical utility across the SCC.

Results and interpretation: A total of 41 studies were identified in cervical, head and neck and anal SCC and we discuss the common signals from the results across the different tumor sites. Our results not only confirm the strong clinical potential but also emphasize an urgent need to coordinate studies to allow for relevant sample sizes and statistical validations.