Discordance of p16 and HPV DNA/RNA Status: Prognostic Implication in Squamous Cell Oropharyngeal Carcinoma

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In a study reported in The Lancet Oncology, Hisham Mehanna, FRCS, and colleagues found that concordance and discordance of p16 immunohistochemistry and human papillomavirus (HPV) DNA/RNA testing were associated with different outcomes among patients with squamous cell oropharyngeal carcinoma.

Hisham Mehanna, FRCS

Hisham Mehanna, FRCS

Study Details

The study involved individual patient data from 13 eligible studies in 13 cohorts of patients from the United Kingdom, Canada, Denmark, Sweden, France, Germany, the Netherlands, Switzerland, and Spain. 

Key Findings

Among 7,654 patients included in the analysis, 3,560 were p16-negative/HPV-negative; 289 were p16-negative/HPV-positive; 415 were p16-positive/HPV-negative; and 3,390 were p16-positive/HPV-positive.

The proportions of p16-positive patients who were HPV-negative differed significantly by geographic region, with the highest discordant rates observed in areas with the lowest HPV-attributable fractions (proportions of patients with oropharyngeal cancer caused by HPV; r = –0.744, P = .0035).

The proportion of patients with p16-positive/HPV-negative cancer was highest in subsites outside the tonsil and base of tongue (29.7% vs 9.0%, P < .0001).

Overall survival at 5 years and adjusted hazard ratios vs p16-positive/HPV-positive cases were:  

  • 1% (95% confidence interval [CI] = 79.5%–82.7%) for p16-positive/HPV-positive patients
  • 2% (95% CI = 46.6%–60.8%) for p16-negative/HPV-positive patients (hazard ratio [HR] = 3.15)
  • 7% (95% CI = 49.2%–60.9%) for p16-positive/HPV-negative patients (HR = 2.69)
  • 4% (95% CI = 38.6%–42.4%) for p16-negative/HPV-negative patients (HR = 4.05; overall P < .0001).

Disease-free survival at 5 years and adjusted hazard ratios vs p16-positive/HPV-positive cases were:

  • 3% (95% CI = 82.9%–85.7%) for p16-positive/HPV-positive patients
  • 1% (95% CI = 64.7%–78.2%) for p16-negative /HPV-positive patients (HR = 2.36)
  • 9% (95% CI = 62.5%–73.7%) for p16-positive /HPV-negative patients (HR = 1.92)
  • 8% (95% CI = 58.8%–62.9%) for p16-negative/HPV-negative patients (HR = 3.27; overall P < .0001).

Prognostic findings were similar across all European subregions.

The investigators concluded, “Patients with discordant oropharyngeal cancer (p16-negative/HPV-positive or p16-positive/HPV-negative) had a significantly worse prognosis than patients with p16-positive/HPV-positive oropharyngeal cancer, and a significantly better prognosis than patients with p16-negative/HPV-negative oropharyngeal cancer. Along with routine p16 immunohistochemistry, HPV testing should be mandated for clinical trials for all patients (or at least following a positive p16 test) and is recommended where HPV status might influence patient care, especially in areas with low HPV-attributable fractions.”

Dr. Mehanna, of the Institute for Head and Neck Studies and Education, University of Birmingham, UK, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the European Regional Development Fund, Generalitat de Catalunya, National Institute for Health Research (NIHR) UK, Cancer Research UK, Medical Research Council UK, and The Swedish Cancer Foundation and Stockholm Cancer Society. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.