Detection of HPV16/18 E6 Oncoproteins in Head and Neck Squamous Cell Carcinoma Using a Protein Immunochromatographic Assay

• Published in: The Laryngoscope 2021-05, Vol.131 (5), p.1042-1048
• Main Authors: Menegaldo, Anna, Schroeder, Lea, Holzinger, Dana, Tirelli, Giancarlo, Dal Cin, Elisa, Tofanelli, Margherita, Rigo, Stefania, Mantovani, Monica, Stellin, Marco, Del Mistro, Annarosa, Dei Tos, Angelo P., Guerriero, Angela, Niero, Monia, Borsetto, Daniele, Da Mosto, Maria C., Polesel, Jerry, Pawlita, Michael, Waterboer, Tim, Boscolo‐Rizzo, Paolo
• Format: Article
• Language: English
• Subjects: Aged; carcinoma of unknown primary; Cross-Sectional Studies; DNA-Binding Proteins - immunology; DNA-Binding Proteins - isolation & purification; E6 oncoprotein; Feasibility Studies; Female; Head & neck cancer; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - surgery; Head and Neck Neoplasms - virology; Human papillomavirus; Human papillomavirus 16 - immunology; Human papillomavirus 16 - isolation & purification; Human papillomavirus 18 - immunology; Human papillomavirus 18 - isolation & purification; Humans; Immunoassay - instrumentation; Immunoassay - methods; Laryngoscopy; Lymphatic Metastasis - pathology; Lymphatic Metastasis - therapy; Male; Metastasis; Middle Aged; neck metastasis; Neoplasms, Unknown Primary - pathology; Neoplasms, Unknown Primary - surgery; Neoplasms, Unknown Primary - virology; Oncogene Proteins, Viral - immunology; Oncogene Proteins, Viral - isolation & purification; Oropharyngeal squamous cell carcinoma; Papillomavirus Infections - diagnosis; Papillomavirus Infections - pathology; Papillomavirus Infections - surgery; Papillomavirus Infections - virology; Reagent Kits, Diagnostic; Repressor Proteins - immunology; Repressor Proteins - isolation & purification; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - pathology; Squamous Cell Carcinoma of Head and Neck - surgery; Squamous Cell Carcinoma of Head and Neck - virology; Throat cancer
• ISSN: 0023-852X; 1531-4995
• DOI: 10.1002/lary.29184

Objectives/Hypothesis The accurate diagnostic assessment of clinically relevant human papillomavirus (HPV) infections in patients with head and neck squamous cell carcinoma represents an urgent unmet medical need. The aim of this study was to determine feasibility, accuracy, and clinical significance of HPV16/18 E6 oncoprotein detection on cytological specimens from oropharyngeal squamous cell carcinoma (OPSCC) and neck lymph node metastasis of SCC from unknown primary tumor (CUP) via a protein immunochromatographic assay. Study Design Cross‐sectional study. Methods Cytological specimens from primary tumor and neck metastases were collected from 34 patients with OPSCC or CUP and applied to a lateral flow format test that detects HPV16 and HPV18 E6 oncoproteins. E6 oncoprotein positivity or negativity in these specimens was compared to the specimens' “HPV‐driven” reference status, defined by presence of HPV‐DNA in combination with p16INK4a overexpression and/or HPV E6 seropositivity. Results Eighteen of 29 OPSCC (62%) and three of five CUP (60%) were HPV‐driven according to our reference method. The E6 oncoprotein lateral flow test had a sensitivity of 94% (95% CI: 70%–100%) and a specificity of 100% (95% CI: 66%–100%) on primary tumor, and a sensitivity of 88% (95% CI: 64%–99%) and a specificity of 100% (95% CI: 74%–100%) on neck metastases. Test agreement between the E6 lateral flow test and the clinical reference method, HPV‐DNA plus p16INK4a was excellent, both for primary lesion and neck metastases. Conclusions We found the detection of HPV16/18 E6 oncoproteins to be a feasible, highly reliable, and low‐invasive method to assess “HPV‐driven” status in OPSCC and CUP. Level of Evidence II Laryngoscope, 131:1042–1048, 2021