The Utility of Tumor Tissue–Modified Viral HPV DNA Testing for HPV ‐Associated Non‐Oropharyngeal Squamous Cell Carcinoma of the Head and Neck

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BACKGROUND: Tumor tissue-modified viral (TTMV) human papillomavirus (HPV) DNA testing has high diagnostic and surveillance performance in HPV-associated oropharyngeal squamous cell carcinoma, but its utility in HPV-associated non-oropharyngeal (non-OP) head and neck squamous cell carcinoma (HNSCC) is not well defined. METHODS: We performed a retrospective cohort study of patients with biopsy-confirmed HPV-positive non-OP HNSCC who underwent TTMV-HPV DNA testing at a single tertiary academic center from April 2020 to January 2025. Diagnostic performance was assessed for pretreatment testing, and surveillance performance was assessed per test and per patient. RESULTS: The diagnostic cohort included 19 patients and demonstrated 80% sensitivity and 100% specificity. The surveillance cohort included 15 patients who underwent 32 tests. Per-test surveillance sensitivity was 87%, specificity 100%, positive predictive value 100%, and negative predictive value 89%. Per-patient surveillance sensitivity was 86%, specificity 100%, positive predictive value 100%, and negative predictive value 89%. In two patients, positive surveillance tests preceded clinical or radiographic recurrence by 18 and 110 days. CONCLUSIONS: TTMV-HPV DNA testing demonstrated strong diagnostic and surveillance performance in HPV-associated non-OP HNSCC and may be a useful adjunct in posttreatment surveillance.

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