Performance and Cost-Effectiveness of Tumor Tissue-Modified Viral (TTMV)-Human Papillomavirus (HPV) DNA for Surveillance of HPV-Associated Oropharyngeal Cancer Compared With Standard Positron Emission Tomography (PET)

Introduction: The standard of care for surveillance of human papillomavirus (HPV)-associated oropharyngeal cancer squamous cell carcinoma (OPSCC) is post-treatment positron emission tomography/computed tomography (PET/CT) imaging. There has been increasing interest in utilizing plasma tumor tissue-modified viral (TTMV)-HPV DNA as part of the diagnostic and surveillance paradigm. Methodology: In this single-institution retrospective analysis, we assessed the performance and cost-effectiveness of surveillance TTMV-HPV DNA in HPV-associated OPSCC among patients who underwent definitive or adjuvant radiation treatment. Patients included in our analysis underwent a three-month post-treatment PET scan and three-month TTMV-HPV DNA testing, with subsequent testing per the provider's discretion at follow-up. Markov decision tree analysis was performed to evaluate the cost-benefit of using TTMV-HPV DNA testing as part of the surveillance paradigm, particularly when a PET/CT image was deemed equivocal. Results: From 2018 to 2023, 68 patients with HPV-associated OPSCC underwent post-treatment surveillance with PET/CT and TTMV-HPV DNA testing. For PET/CT surveillance, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 83.3%, 90.3%, 45.5%, and 98.2%, respectively. For surveillance with TTMV-HPV DNA, the sensitivity, specificity, PPV, and NPV were 66.7%, 98.4%, 80.0%, and 96.8%, respectively. Using Markov decision tree analysis, we assessed the net monetary benefit (NMB) of additional TTMV-HPV DNA testing when PET/CT was equivocal and the NMB of upfront TTMV-HPV DNA testing alongside PET/CT. In both scenarios, we noted that the NMB was greater with TTMV-HPV DNA (scenario 1: $16,925; scenario 2: $16,809) than with repeat PET/CT (scenario 1: $15,575; scenario 2: $15,504). Conclusions: These findings suggest that TTMV-HPV DNA testing performs as well as, and is potentially more cost-effective than, gold-standard PET/CT imaging for the surveillance of HPV-associated OPSCC. Future randomized studies are needed to determine whether TTMV-HPV DNA testing alone could be sufficient for the surveillance of treated HPV-associated OPSCC.