Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Background: Tumor tissue modified viral-human papillomavirus DNA (TTMV-HPV DNA) testing has been shown to have good sensitivity and specificity for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). This study updates our institution's previous report on the performance of this liquid biopsy test and includes the largest known number of tumor tissue-modified viral (TTMV) HPV DNA tests conducted at a single institution.
Methods: In this retrospective cohort study, we assessed the clinical efficacy of plasma TTMV-HPV DNA testing in OPSCC patients treated at a single tertiary care center from April 2020 to September 2024. Patients were divided into two groups: a diagnostic cohort, which included those who underwent at least one TTMV-HPV DNA test before beginning primary therapy, and a surveillance cohort, which included those who had at least one test following the completion of definitive or salvage therapy. Positive tests and negative tests that occurred within three months of a molecularly and pathologically confirmed diagnosis of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) were classified as true positives and false negatives, respectively. Primary outcome measures were sensitivity and specificity in both diagnostic and surveillance settings.
Results: Among 751 patients, 252 were in the diagnostic cohort and 518 were in the surveillance cohort with an overall 1,471 TTMV-HPV DNA tests analyzed. Median age for all patients was 64 and 84.1% were male. In the diagnostic cohort, based on 266 tests, TTMV-HPV DNA testing achieved a per-test sensitivity of 89.1% (212 true positive tests out of 238 positive cases) and a per-test specificity of 96.4% (27 true negative tests out of 28 negative cases) for HPV-associated OPSCC. 115 patients in this study had pathologically confirmed recurrence. In the surveillance setting, based on a total of 1205 tests, TTMV-HPV DNA demonstrated a sensitivity of 87.5% (63 true positives out of 72 positive cases) and a specificity of 98.8% (1119 true negatives out of 1133 negative cases).
Discussion: This study again demonstrates that TTMV-HPV DNA testing has excellent specificity in both diagnostic and surveillance settings. Sensitivity for both settings suggests that over 10% of tests for a patient with active disease may be a false negative.
Conclusion: TTMV-HPV DNA testing shows high specificity and utility in diagnosing and surveilling HPV-associated OPSCC. Despite the sensitivity under 90%, this test remains a very valuable tool in the pretreatment and surveillance settings.