Circulating tumor HPV DNA in the management of HPV+ oropharyngeal cancer and its correlation with MRI

• Published in: Head & neck Vol. 46; no. 9; pp. 2206 - 2213
• Main Authors: Campo, Flaminia, Paolini, Francesca, Manciocco, Valentina, Moretto, Silvia, Pichi, Barbara, Moretti, Claudio, Blandino, Giovanni, De Pascale, Valentina, Benevolo, Maria, Pimpinelli, Fulvia, Vidiri, Antonello, Marzi, Simona, Ruggiero, Sergio, Terrenato, Irene, Iocca, Oreste, Venuti, Aldo, Pellini, Raul
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-09-2024; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; circulating tumor DNA; Circulating Tumor DNA - blood; Diagnosis; Disease management; DNA, Viral - blood; Female; Human papillomavirus; Humans; liquid biopsy; Lymph nodes; Lymphatic Metastasis; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Metastases; Middle Aged; MRI; Neoplasm Recurrence, Local - virology; Oropharyngeal cancer; Oropharyngeal Neoplasms - blood; Oropharyngeal Neoplasms - diagnostic imaging; Oropharyngeal Neoplasms - pathology; Oropharyngeal Neoplasms - virology; oropharyngeal squamous cell carcinoma; Papillomavirus Infections - complications; Papillomavirus Infections - diagnosis; Patients; Polymerase Chain Reaction; Predictive Value of Tests; Sensitivity and Specificity; Squamous cell carcinoma; Throat cancer; Tumors; MRI; liquid biopsy; human papillomavirus; oropharyngeal squamous cell carcinoma; circulating tumor DNA
• ISSN: 1043-3074; 1097-0347; 1097-0347
• DOI: 10.1002/hed.27866

Background
First aim was to compare ddPCR assays of ctHPVDNA with p16 IHC and qualitative HPV PCR. Second aim was to carry out longitudinal blood sampling to test for association of ctHPVDNA with histological confirmed recurrence. Third aim was to perform a multidimensional assessment which included: (1) clinical features; (2) ctHPVDNA; (3) MRI‐based tumor size measurements of primary tumor (PT) and cervical lymph node metastases (CLNM).
Methods
Plasma samples were collected before treatment and during follow‐up, and ddPCR assay comprising E6 of HPV16 and HPV 33 and HPV 35 was used.
Results
Present study was conducted at diagnosis in 117 patients and revealed a ctHPVDNA sensitivity of 100% (95% CI 95.5–100) and a specificity of 94.4 (95% CI 81.3–99.3), positive predictive value (PPV) of 94.4 (95% CI 81.3–99.3), and negative predictive value (NPP) of 100% (95% CI 89.7–100). During follow‐up ctHPVDNA had a sensitivity of 100% (95% CI 72.1–100)% and specificity of 98.4% (95% CI 91.7–100)%, PPV% of 90.9% (95% CI 62.3–98.4) and NPV% of 100% (95% CI 94.3–100) for ability to detect recurrence. Correlation between both the CLNM volume and the sum of PT and CLNM volume was observed.
Conclusions
ctHPVDNA was superior to p16 in identification of HPV‐OPSCC at diagnosis. Introduction of ctHPVDNA, beyond diagnostic setting, represents a great opportunity to improve follow‐up protocol of OPSCC patients.