Marisa Mena (Spain)
Catalan Institute of Oncology (ICO) - Bellvitge Biomedical Research Institute (IDIBELL) Cancer Epidemiology Research ProgramPresenter of 1 Presentation
DIAGNOSTIC ACCURACY OF HPV-DNA/P16INK4A DOUBLE TESTING IN NON-OROPHARYNGEAL HEAD AND NECK CANCER: RESULTS FROM THE ICO INTERNATIONAL STUDY (ID 1150)
- Marisa Mena (Spain)
- Sara Tous (Spain)
- Beatriz Quiros (Spain)
- Omar Clavero (Spain)
- Maria Alejo (Spain)
- Miren Taberna (Spain)
- Xavier Leon (Spain)
- Belen Lloveras (Spain)
- Llucia Alos (Spain)
- Hisham Mehanna (United Kingdom)
- Wim G. Quint (Netherlands)
- Michael Pawlita (Germany)
- Miquel Ángel Pavón (Spain)
- Nubia Muñoz (Colombia)
- Silvia De Sanjose (United States of America)
- Francesc Xavier Bosch José (Spain)
- Laia Alemany Vilches (Spain)
Abstract
Introduction
For the diagnosis of HPV-driven non-oropharyngeal head and neck cancer (HNC), tests or test algorithms have not been validated so far.
Methods
Formalin-fixed, paraffin-embedded cancer tissues of oral cavity (OCC), oropharyngeal (OPC), and laryngeal (LC) cancer were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. HPV-DNA positive and a random sample of HPV-negative samples were subject to HPV E6*I-mRNA detection and p16INK4a immunohistochemistry. Three different cut-offs of intense nuclear and cytoplasmic staining were evaluated for p16INK4a overexpression: >25%, >50% and >70%. Accuracy of HPV-DNA/p16INK4a double testing was assessed by estimating the sensitivity, specificity, odds ratios, and area under the curve (AUC) taking as gold-standard E6*I-mRNA positivity, by HNC site.
Results
169 OCC, 431 OPC and 129 LC out of 3680 HNC with valid HPV-DNA results were tested for p16INK4a and E6*I-mRNA. HPV-DNA/p16INK4a double testing showed higher AUC than p16INK4a alone in OPC for all cut-offs (p-values < 0. 05), due to an increase of specificity. In OCC and LC, the increase of specificity was also observed, although not being statistically significant. Sensitivities of HPV-DNA/p16INK4a and p16INK4a alone were much lower for LC compared to OCC and OPC (56.3%-59.4% versus 80.9% and 85.5%, respectively). When restricting the analysis to HPV16-positive cases, an improvement for HPV-DNA/p16INK4a double testing than p16INK4a positivity alone was observed in OPC for all cut-offs (p-values <0.001) and in OCC, although not reaching the statistical significance in this case neither (p-value 0.139).
Conclusions
HPV-DNA/p16INK4a double testing may be useful for HPV-driven OCC diagnosis although more experiments with higher number of cases are needed. Considering only HPV16-positive cases may improve the test accuracy. When assessing HPV-role on non-oropharyngeal HNC, a distinction between OCC and LC must be made.