Evaluating Clinical Factors Including HPV Clearance on Survival Outcomes in HPV+ Oropharyngeal Carcinoma

Background: The relationship between detectable circulating tumor DNA levels and clinical outcome following definitive therapy in patients with human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinoma has not been well established. Methods: In this retrospective analysis of patients with HPV-positive oropharyngeal squamous cell carcinoma seen from 2016 to 2024 at a single institution, 88 patients met inclusion criteria with baseline-positive tumor tissue-modified viral HPV DNA (TTMV-HPV DNA) testing and post-treatment testing performed. Results: Of the 88 patients included in the survival analysis, 77 had undetectable tumor tissue-modified viral human papillomavirus DNA after treatment, while 11 had positive (detectable) tumor tissue-modified viral human papillomavirus DNA. TTMV-HPV DNA positivity after treatment was associated with worse 1-year and 2-year overall survival outcomes, at 63.5% (37.7-100, p = 0.022) and 50.8% (25.7-100, p = 0.017) compared to 100% and 96.4% (91.6-100, p = 0.017) in patients with undetectable TTMV-HPV DNA. Inability to clear TTMV-HPV DNA after treatment was associated with worse progression-free survival, at 45.0% (95% CI 21.8-92.7, p = 0.009) at 1 year and 11.3% (95% CI 1.8-71.2, p = <0.001) at 2 years compared to 93% (95% CI 87.3-99.1) and 84.7% (95% CI, 76.3-94.0) in patients with cleared TTMV-HPV DNA after treatment. Conclusion: Tumor tissue-modified viral human papillomavirus DNA positivity after definitive treatment was associated with worse survival and disease recurrence outcomes compared to that in patients with undetectable post-treatment TTMV-HPV DNA. Prospective studies are warranted to further establish the clinical utility of TTMV-HPV DNA testing and its use in surveillance, treatment intensification, or de-intensification.