Circulating Tumor HPV DNA for Surveillance of HPV-Positive Oropharyngeal Squamous Cell Carcinoma

Abstract

ImportanceHuman papillomavirus (HPV)–positive oropharyngeal squamous cell carcinoma has an overall favorable prognosis, yet a subset of patients will experience devastating disease recurrence. Current surveillance standards for detection of recurrent disease are imperfect. There is growing interest in improving detection of recurrent disease through the use of plasma-based assays able to detect circulating tumor HPV DNA.ObservationsAlthough most circulating tumor HPV DNA assays remain in the research domain, the circulating tumor tissue–modified viral HPV DNA assay became commercially available in the United States in early 2020 and has been increasingly used in the clinical setting. With the rapidly increasing incidence of HPV-positive oropharyngeal squamous cell carcinoma and concomitant expansion of biomarker capabilities for this disease, it is critical to reexamine current posttreatment surveillance practices and to determine whether emerging technologies may be used to improve outcomes for a growing survivor population. However, caution is advised; it is not yet known whether biomarker-based surveillance is truly beneficial, and as is true with any intervention, it has the capacity to cause harm.Conclusions and RelevanceUsing Margaret Pepe’s classic 5 phases of biomarker development for early detection of cancer as a framework, this article reviews the current state of knowledge, highlights existing knowledge gaps, and suggests research that should be prioritized to understand the association between biomarker-based surveillance and patient outcomes. Specific attention is paid to the commercially available tumor tissue–modified viral HPV DNA assay, given its increasing clinical use. This review may serve as a road map for future research and a guide for clinicians considering its adoption in practice. Enrollment of patients into clinical trials incorporating biomarker-based surveillance should be prioritized.

Human papillomavirus circulating tumor DNA assays as a mechanism for head and neck cancer equity in rural regions of the United States

“…It remains unclear how to optimally work up a survivor with detectable HPV ctDNA in order to localize and pathologically confirm a recurrence. And, according to the largest cohort study published to date, the sensitivity of HPV ctDNA for recurrence is 92.5% when considered on a per-test basis, and 87.3% when considered on a per-patient basis ( 67 , 68 ). These results are very favorable, but HPV-OPC can indeed recur without a corresponding or preceding spike in ctDNA.…”

Personalized ctDNA for Monitoring Disease Status in Head and Neck Squamous Cell Carcinoma

“…Recent research efforts have focused on exploring the potential of ctDNA in virally driven human papillomavirus (HPV)–associated oropharyngeal cancers ( 5 ) and Epstein–Barr virus–positive nasopharyngeal carcinoma ( 6 , 7 ). Viral DNA permits detection of highly tumor-specific gene sequences that should otherwise be absent in circulation.…”