Novel HPV Associated Oropharyngeal Squamous Cell Carcinoma Surveillance DNA Assay Cost Analysis.

OBJECTIVES: We aim to propose a modified surveillance strategy using a novel blood assay that detects plasma circulating tumor-specific HPV DNA with reported 100% NPV and 94% PPV as the main method of detection to understand the cost implications of potentially avoiding routine imaging and surveillance visits at our institution. METHODS: We performed a retrospective chart review focusing on recurrences in p16+ patients with OPSCC and defined two surveillance strategies: "Strategy A", follow-up visits with flexible laryngoscopy (FL) plus regular imaging studies; "Strategy B", follow-up visits with FL plus regular NavDx assays and imaging used at the discretion of the physician(s) in cases of high clinical suspicion. RESULTS: Of the p16+ OPSCC patients (n = 214), 23 had confirmed recurrence (11%). Standard work-flow model determined 72 imaging studies and 2198 physical examinations with FL were needed to detect one recurrence. Potential individual patient cost reduction during surveillance was 42%. CONCLUSION: Implementing NavDx for HPV + OPSCC surveillance would benefit patients by reducing costs and unnecessary diagnostic testing. LEVEL OF EVIDENCE: Step/Level 3 Laryngoscope, 133:3006-3012, 2023.

Human hepatocyte transplantation corrects the inherited metabolic liver disorder arginase deficiency in mice.

The transplantation, engraftment, and expansion of primary hepatocytes have the potential to be an effective therapy for metabolic disorders of the liver including those of nitrogen metabolism. To date, such methods for the treatment of urea cycle disorders in murine models has only been minimally explored. Arginase deficiency, an inherited disorder of nitrogen metabolism that presents in the first two years of life, has the potential to be treated by such methods. To explore the potential of this approach, we mated the conditional arginase deficient mouse with a mouse model deficient in fumarylacetoacetate hydrolase (FAH) and with Rag2 and IL2-Rγ mutations to give a selective advantage to transplanted (normal) human hepatocytes. On day -1, a uroplasminogen-expressing adenoviral vector was administered intravenously followed the next day with the transplantation of 1 × 106 human hepatocytes (or vehicle alone) by intrasplenic injection. As the initial number of administered hepatocytes would be too low to prevent hepatotoxicity-induced mortality, NTBC cycling was performed to allow for hepatocyte expansion and repopulation. While all control mice died, all except one human hepatocyte transplanted mice survived. Four months after hepatocyte transplantation, 2 × 1011 genome copies of AAV-TBG-Cre recombinase was administered IV to disrupt endogenous hepatic arginase expression. While all control mice died within the first month, human hepatocyte transplanted mice did well. Ammonia and amino acids, analyzed in both groups before and after disruption of endogenous arginase expression, while well-controlled in the transplanted group, were markedly abnormal in the controls. Ammonium challenging further demonstrated the durability and functionality of the human repopulated liver. In conclusion, these studies demonstrate that human hepatocyte repopulation in the murine liver can result in effective treatment of arginase deficiency.