Circulating HPV Tumor DNA as a Pretreatment Biomarker in Oropharyngeal Cancer: JAMA

While the presence or absence of TTMV DNA may predict the presence or absence of HPV-positive OPSCC cancer cells, the importance of ctDNA concentration, measured as fragments/mL, in these patients is less understood.

The study by Rettig et al evaluated other potential contributors to TTMV HPV DNA levels. They examined if other tumor metabolic activity (positron emission tomography standardized update value), host genetics (sex), or markers of tumor biology (HPV subtype, lymphovascular invasion) might also contribute to the fragment concentration, with mixed results. It is also unclear why some patients with biopsy-proven disease still have undetectable ctDNA, as seen in 89% of the cohort in this study, a finding also observed in other published HPV-positive OPSCC cohorts. This is despite the fact that tumor DNA can be detected sometimes years prior to cancer development. There remain many unanswered questions in understanding TTMV DNA levels.

These considerations of pretreatment ctDNA levels are not just academic. While the survival of patients with HPVpositive OPSCC is fortunately more favorable compared with tobacco or alcohol–associated p16-negative OPSCC, a subset of patients with HPV-positive OPSCC still die of their disease. Head and neck disease teams everywhere are endeavoring, on the one hand, to de-escalate treatment intensity for favorable prognosis in HPV-positive OPSCC, while on the other hand also seeking strategies to identify patients a priori as poor responders to therapy and find alternatives. Pretreatment biomarkers like HPV TTMV DNA offer a pathway to addressing this challenge. Understanding the circumstances that drive detectable HPV TTMV DNA pretreatment will better inform treatment decisions and prognosis. Indeed, an ongoing phase 2 clinical trial is evaluating the use of pretreatment HPV TTMV DNA levels to risk-adapt patients for radiation de-escalation.

Use of HPV ctDNA as a pretreatment biomarker provides promising data to help better guide the care of patients with HPV-positive OPSCC. Source: Jeffrey C. Liu, JAMA Otolaryngology–Head & Neck Surgery doi:10.1001/jamaoto.2022.3331