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Proffered Paper - Head & Neck cancer

911O - Performance of dual p16 and HPV testing for determining prognosis in cancer of the oropharynx, the EPIC-OPC Study

Date

19 Sep 2020

Session

Proffered Paper - Head & Neck cancer

Presenters

Miren Taberna

Citation

Annals of Oncology (2020) 31 (suppl_4): S599-S628. 10.1016/annonc/annonc277

Authors

M. Taberna1, H. Mehanna2, S. Tous3, J. Brooks2, C. von Buchwald4, M. Mena5, N. Batis2, R.H. Brakenhoff6, R. Baatenburg de Jong7, J.P. Klussmann8, T. Dalianis9, H. Mirghani10, A. Schache11, J.A. James12, S.H. Huang13, M.A. Broglie14, M. Hoffmann15, L. Alemany3

Author affiliations

  • 1 Medical Oncology Department, Head And Neck Cancer Unit, Institut Català d'Oncologia-Hospital Duran i Reynals, 08907 - Hospitalet de Llobregat/ES
  • 2 Institute Of Cancer And Genomic Sciences Robert Aitken Building, The University of Birmingham Institute for Cancer Studies, B15 2TT - Birmingham/GB
  • 3 Cancer Epidemiology Research Program, Institut Català d'Oncologia-Hospital Duran i Reynals, 08908 - Hospitalet de Llobregat/ES
  • 4 Department Of Otolaryngology, Head And Neck Surgery, Faculty of Health and Medicine Sciences, University of Copenhagen, 2100 - Copenhagen/DK
  • 5 Cancer Epidemiology Research Program (cerp), Institut Català d'Oncologia (ICO) - Bellvitge Biomedical Research Institute (IDIBELL), 08908 - Hospitalet de Llobregat/ES
  • 6 Department Of Otolaryngology/head And Neck Surgery, VUmc Cancer Center Amsterdam, Amsterdam/NL
  • 7 Department Of Otorhinolaryngology, Head And Neck Surgery, ErasmusMC Cancer Center, Rotterdam/NL
  • 8 Department Of Otorhinolaryngology, Head And Neck Surgery, University of Giessen, DE-35392 - Giessen/DE
  • 9 Oncology – Pathology, Cancer Center Karolinska, Stockholm/SE
  • 10 Department Of Head And Neck Oncology, Gustave Roussy Cancer Campus, 94805 - Villejuif/FR
  • 11 Department Of Molecular And Clinical Cancer Medicine, University of Liverpool Cancer Research Centre Roy Castle Building, L3 9TA - Liverpool/GB
  • 12 Patrick G Johnston Centre For Cancer Research, Queen’s University Belfast, Belfast/GB
  • 13 Radiation Oncology, Princess Margaret Cancer Center, Toronto/CA
  • 14 Department Of Otorhinolaryngology-head And Neck Surgery, University Hospital Zurich, Zurich/CH
  • 15 Department Of Otorhinolaryngology, Head And Neck Surgery, Christian-Albrechts-University Kiel, Kiel/DE
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Resources

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Abstract 911O

Background

p16INK4a (p16) immunostaining is the most widely implemented technique in clinical settings for determining HPV causation and HPV-related prognosis biomarker of oropharyngeal cancer (OPC). A subset of p16+ OPC are HPV-; and their prognosis is still unclear. The aim of this study is to clearly define the proportion, determinants and prognosis of OPC patients who are p16+/HPV-.

Methods

We established an international consortium comprising 13 cohorts of OPC patients with data on p16, HPV, demographics, tobacco/alcohol use and clinical data. A centralized individual patient data reanalysis was performed. Multivariate models were used to evaluate factors associated with HPV status as defined by different HPV-assessment methods. Proportional-hazards models were used to compare the risk of death (OS) among HPV-related and un-related OPC.

Results

In total 7702 patients from 9 different countries were included. The percentage of positive cases was 49.7%, 47.9% and 44.3% for p16+, HPV+ and p16+/HPV+, respectively. Among p16+ cases, 10.9% were HPV-. This proportion differed significantly by cohorts and geographic areas (p-value<0.001) and was lowest in the highest prevalence areas (Table). Compared to p16-/HPV- tumors, p16+/HPV+was the biomarker with strongest prognostic value (aHR 0.28, 95%CI 0.25-0.31), followed by p16+/HPV- (aHR=0.65, 95%CI 0.56-0.76), and p16-/HPV+ (HR=0.72, 95%CI 0.60-0.86). Disease-free/OPC-specific survival analyses will be presented at the congress. Table: 911O

p16+/HPV- by region and cohort from the EPIC-OPC study

Region/Cohort Total N P16+ N P16+/HPV-
N (%)*
North America 186 135 2 1.5
Canada-Toronto 186 135 2 1.5
Northern Europe 6380 3320 351 10.6
Denmark-Copenhagen 2169 1324 123 9.3
UK-Birmingham 816 499 58 11.6
UK-Liverpool 252 152 12 7.9
UK-Belfast 232 95 11 11.6
The Netherlands-Amsterdam/Rotterdam 1203 388 48 12.4
Germany-Giessen 704 235 40 17.0
Germany-Cologne 205 111 17 15.3
Germany-Kiel 126 58 11 19.0
Sweden-Stockholm 539 375 24 6.4
Switzerland-Zurich 134 83 7 8.4
Southern Europe 1136 370 63 17.0
France-Paris 275 275 275 12.7
Spain-Barcelona 861 95 28 29.5
All 7702 3825 416 10.9

*p16+/HPV- percent among p16 tested.

Conclusions

p16+/HPV+ tumors showed the highest OS magnitude of association compared with other biomarkers combinations. Using p16 immunostaining alone, 11% OPC patients would be incorrectly classified as HPV-related OPC according to TNM-8 staging, and with risk of misclassification for de-escalation in clinical trials, particularly in regions with lower attributable fractions of HPV.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Catalan Institute of Oncology.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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