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Prognostic Implications of HPV Cell-Free DNA Serial Testing During Follow-Up of p16 Positive Oropharyngeal Squamous Cell Carcinoma After Curative-Intent Treatment

Year: 2025

Type: article

Abstract: INTRODUCTION: Plasma circulating HPV cell-free DNA has high sensitivity and specificity for the detection of HPV-mediated oropharyngeal squamous cell carcinoma. We investigated the clinical significance of serial testing after curative-intent treatments. MATERIALS AND METHODS: Patients with concordant p16 positive tumour or neck node biopsy and positive high-risk HPV plasma cell-free DNA were prospectively recruited. HPV cell-free DNA were obtained using digital droplet polymerase chain reaction (ddPCR) and were collected at diagnosis and at every clinical follow-up. Three months after completion of curative-intent treatments, patients were stratified according to treatment response on computed tomography. Complete responders (CR) were followed-up clinically, partial responders (PR) underwent further imaging and surgical/medical management if appropriate, patients with progressive disease (PD) received palliative treatments. RESULTS: A hundred and fourteen patients were included and 717 HPV cfDNA ddPCR samples were analysed during a median follow-up of 103 weeks (IQR, 40.2-147.8). Ninety (78.9%) patients were classified as CR, 18 (15.8%) as PR and all except one, who was rapidly diagnosed with PD, had negative HPV ddPCR at 12 weeks follow-up; 6 (5.3%) had PD and all except one had positive HPV ddPCR. Eleven had recurrent disease, 6 in the CR group (6.6%) and 5 among PR (27.7%). Ninety patients had consistently negative HPV ddPCR at all time points and one developed a recurrence (NPV 99%, 95% C.I., 93.2-99.8%). Eighteen patients developed positive HPV ddPCR and 10 developed recurrent disease (PPV 55%, 95% C.I., 38.6-71.4%). Ten patients had two consecutively positive HPV ddPCR and all had proven disease (PPV 100%, 95% C.I., 69.2-100%). Nine patients had transiently positive HPV ddPCR and none developed disease at that time. CONCLUSIONS: Post-treatment HPV ddPCR reflected treatment response on imaging and serial testing had high PPV and NPV in detecting recurrent disease.

Source: Clinical Oncology

DOI: 10.1016/j.clon.2025.103807