Comparison of Molecular Assays for HPV Testing in Oropharyngeal Squamous Cell Carcinomas: A Population-Based Study in Northern Ireland



Craig, Stephanie G, Anderson, Lesley A, Moran, Michael, Graham, Laura, Currie, Keith, Rooney, Keith, Robinson, Max, Bingham, Victoria, Cuschieri, Kate S, McQuaid, Stephen
et al (show 6 more authors) (2020) Comparison of Molecular Assays for HPV Testing in Oropharyngeal Squamous Cell Carcinomas: A Population-Based Study in Northern Ireland. CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 29 (1). pp. 31-38.

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Abstract

Background: Determination of human papillomavirus (HPV) status has become clinically relevant for patient stratification under UICC TNM8 staging. Within the United Kingdom, a combination of p16 IHC and HPV DNA-ISH is recommended for classifying HPV status. This study will assess a series of clinically applicable second-line molecular tests to run in combination with p16 IHC to optimally determine HPV status. Methods: The ability of HPV RNA-ISH, HPV DNA-ISH, and HPV DNA-PCR to identify p16-positive/HPV-positive patients was investigated in a population-based oropharyngeal squamous cell carcinoma (OPSCC) cohort of patients diagnosed in Northern Ireland from 2000 to 2011. Results: Only 41% of the Northern Irish OPSCC patient population was associated with HPV-driven carcinogenesis. Both ISH assays were more specific than the DNA-PCR assay (100% and 95% vs. 67%) and were less likely to be affected by preanalytic factors such as increasing block age. A pooled HPV genotype probe for RNA-ISH was found to be the most accurate molecular assay assessed (95% accuracy) when compared with p16 positivity. Conclusions: Our study demonstrates the advantage of tissue-based molecular assays when determining HPV status in retrospective samples. Specifically, we demonstrate the enhanced sensitivity and specificity of ISH techniques compared with PCR-based methodology when working with formalin-fixed paraffin-embedded tissue, and found HPV RNA-ISH to be the most effective assay for determining HPV status. Impact: As p16 IHC is a relatively inexpensive, accessible, and sensitive test for stratifying patients by HPV status, this study finds that more patients would benefit from first-line p16 IHC followed by specific HPV testing using HPV RNA-ISH to confirm HPV status.

Item Type: Article
Uncontrolled Keywords: Humans, Papillomavirus Infections, Oropharyngeal Neoplasms, DNA, Viral, RNA, Viral, Neoplasm Staging, Prognosis, Immunohistochemistry, In Situ Hybridization, Sensitivity and Specificity, Retrospective Studies, Follow-Up Studies, Age Factors, Middle Aged, Northern Ireland, Female, Male, Cyclin-Dependent Kinase Inhibitor p16, Alphapapillomavirus, Kaplan-Meier Estimate, Human Papillomavirus DNA Tests, Biomarkers, Tumor, Squamous Cell Carcinoma of Head and Neck
Depositing User: Symplectic Admin
Date Deposited: 25 Nov 2019 15:01
Last Modified: 19 Jan 2023 00:19
DOI: 10.1158/1055-9965.EPI-19-0538
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3063422