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

Author:

Campo Flaminia1ORCID,Paolini Francesca23,Manciocco Valentina1,Moretto Silvia1,Pichi Barbara1,Moretti Claudio1,Blandino Giovanni4,De Pascale Valentina5,Benevolo Maria6,Pimpinelli Fulvia7,Vidiri Antonello8,Marzi Simona8,Ruggiero Sergio8,Terrenato Irene9,Iocca Oreste10,Venuti Aldo2,Pellini Raul1

Affiliation:

1. Department of Otolaryngology – Head and Neck Surgery IRCCS Regina Elena National Cancer Institute, Istituti Fisioterapici Ospitalieri (IFO) Rome Italy

2. HPV‐Unit, UOSD Tumor Immunology and Immunotherapy, IRCCS Regina Elena National Cancer Institute Istituti Fisioterapici Ospitalieri (IFO) Rome Italy

3. Department of Biochemical Sciences A. Rossi Fanelli Sapienza University of Rome Rome Italy

4. Oncogenomic and Epigenetic Unit, IRCCS Regina Elena National Cancer Institute Istituti Fisioterapici Ospitalieri (IFO) Rome Italy

5. Translational Oncologic Research, IRCCS Regina Elena National Cancer Institute Istituti Fisioterapici Ospitalieri (IFO) Rome Italy

6. Department of Pathology IRCCS Regina Elena National Cancer Institute Rome Italy

7. Department of Microbiology and Virology, IRCCS San Gallicano Dermatological Institute Istituti Fisioterapici Ospitalieri (IFO) Rome Italy

8. Department of Radiology and Diagnostic Imaging, IRCCS Regina Elena National Cancer Institute Istituti Fisioterapici Ospitalieri (IFO) Rome Italy

9. Clinical Trial Center – Biostatistics & Bioinformatics IRCCS Regina Elena National Cancer Institute Rome Italy

10. Division of Maxillofacial Surgery, Department of Surgical Science University of Torino Torino Italy

Abstract

AbstractBackgroundFirst 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).MethodsPlasma samples were collected before treatment and during follow‐up, and ddPCR assay comprising E6 of HPV16 and HPV 33 and HPV 35 was used.ResultsPresent 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.ConclusionsctHPVDNA 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.

Publisher

Wiley

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