Purpose: Circulating tumor DNA (ctDNA) assays have evolved into transformative tools capable of disrupting current management paradigms, including that of human papillomavirus (HPV)-positive oropharyngeal carcinoma (OPC). Despite readily available assays, guidance on its implementation remains undefined.
Methods: A systematic literature review, an expert physician panel, and patient interviews were used to develop consensus items on circulating tumor HPV DNA (ctHPVDNA) use. A hybrid Delphi approach was applied with California Head and Neck Consortium (CHNC) experts to appraise consensus over iterative rounds of feedback. Voting continued until thematic saturation was achieved.
Results: In total, 33 CHNC experts participated, representing various entities (academic medical center, integrated managed care system, county hospital, Veterans Affairs hospital, community cancer center, private practice). Item development led to 32 statements across five domains, which later expanded to 33 items. Thematic saturation was reached after three rounds, with complete participation (33 of 33 votes) achieved in each round. Of these statements, 63.6% (21 of 33) reached strong consensus, 9.1% (3 of 33) reached consensus, 12.1% (4 of 33) was found to have no consensus, and 15.1% (5 of 33) was rejected. Key statements highlighted the strong consensus that ctHPVDNA was a valuable tool appropriate for diagnosis and surveillance settings, but not for screening or treatment modifications in current clinical practice. Despite the promise of this technology, there was strong consensus that randomized clinical trials should be performed to optimize its use in HPV+ OPC in the setting of potential increased costs.
Conclusion: Using currently available evidence and expertise, we establish a pragmatic framework of consensus recommendations for ctHPVDNA use. Such statements of varying strength will help bridge gaps in knowledge and lead to judicious implementation of assays into clinical practice.