Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC): a multicentre, multinational, individual patient data analysis

Hisham Mehanna ¹, Miren Taberna ², Christian von Buchwald ³

¹Institute of Head and Neck Studies and Education (InHANSE), Institute of Cancer and Genomics Sciences, University of Birmingham, Birmingham, UK.
²Department of Medical Oncology, Catalan Institute of Oncology (ICO), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain.
³Department of Otolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
⁴Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Epidemiology and Public Health, Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.
⁵Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
⁶Otolaryngology-head and neck surgery, Cancer Centre Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Netherlands.
⁷Department of Otolaryngology, Head and Neck Surgery, Erasmus MC Cancer Centre, Rotterdam, Netherlands.
⁸Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Cologne, Cologne, Germany.
⁹Department of Otorhinolaryngology, Head and Neck Surgery, University of Giessen, Giessen, Germany.
¹⁰Department of Oncology-Pathology, Karolinska University Hospital, Stockholm, Sweden.
¹¹Department of Clinical Science, Intervention and Technology, Department of Oto-Rhinolaryngology, Head and Neck Surgery, Karolinska University Hospital, Stockholm, Sweden; Medical Unit Head and Neck, Lung and Skin Cancer, Karolinska University Hospital, Stockholm, Sweden; Department of Surgical Sciences, Section of Otolaryngology and Head and Neck Surgery, Uppsala University, Uppsala, Sweden.
¹²Department of Head and Neck Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
¹³Liverpool Head & Neck Centre, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
¹⁴Precision Medicine Centre of Excellence, Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland, UK; Regional Molecular Diagnostic Service, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
¹⁵Department of Radiation Oncology/Otolaryngology-Head and Neck Surgery, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
¹⁶Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
¹⁷Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University Kiel, Kiel, Germany.

⁰Institute of Head and Neck Studies and Education (InHANSE), Institute of Cancer and Genomics Sciences, University of Birmingham, Birmingham, UK.

The Lancet. Oncology +

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February 16, 2023

View abstract on PubMed

Summary

p16 immunohistochemistry is a common biomarker for oropharyngeal cancer, but discordance with HPV testing exists. Patients with discordant results (p16+/HPV- or p16-/HPV+) have a worse prognosis than p16+/HPV+ cases, but better than p16-/HPV- cases.

Area Of Science

Oncology
Virology
Biomarker Research

Background

p16 immunohistochemistry (p16) is a standard biomarker for human papillomavirus (HPV) causation in oropharyngeal cancer.
Discordance between p16 and HPV status is observed in a subset of oropharyngeal cancer patients.
The prognostic implications of this p16/HPV discordance require further quantification.

Purpose Of The Study

To quantify the extent of discordance between p16 and HPV testing in oropharyngeal cancer.
To evaluate the prognostic significance of discordant p16 and HPV results.
To inform clinical trial design and patient management strategies.

Main Methods

Multicentre, multinational individual patient data analysis of published literature (PubMed, Cochrane).
Inclusion of 13 cohorts (7654 patients) with primary oropharyngeal squamous cell carcinoma and data on p16, HPV, and clinical outcomes.
Multivariable analysis to determine adjusted hazard ratios for survival based on p16/HPV status combinations.

Main Results

415 of 3805 p16-positive patients were HPV-negative (10.9%), with regional variations.
Discordant p16/HPV status was more frequent in oropharyngeal subsites outside the tonsil and base of tongue.
Five-year overall survival rates: p16+/HPV+ (81.1%), p16-/HPV- (40.4%), p16-/HPV+ (53.2%), p16+/HPV- (54.7%).
Five-year disease-free survival rates: p16+/HPV+ (84.3%), p16-/HPV- (60.8%), p16-/HPV+ (71.1%), p16+/HPV- (67.9%).

Conclusions

Patients with discordant p16/HPV results in oropharyngeal cancer have an intermediate prognosis.
HPV testing is recommended alongside p16 immunohistochemistry, especially in regions with low HPV-attributable fractions.
Mandating HPV testing in clinical trials for oropharyngeal cancer is advised to refine prognostic stratification.

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