Classifying patients with oropharyngeal cancer based on p16-positive immunohistochemistry alone is likely “insufficient” in routine clinical practice, according to researchers. 

They found that patients who have discordant p16 and HPV status have worse prognosis than patients who have p16-positive/HPV-positive cancer and better prognosis than patients who have p16-negative/HPV-negative cancer.

These findings were published in The Lancet Oncology

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The researchers analyzed data from 13 studies encompassing 7654 evaluable patients with oropharyngeal cancer. The patients’ median age was 60 years, 74.7% of patients were men, and 78.8% had locally advanced disease. 

Overall, 3.8% of patients had p16-negative/HPV-positive cancer, 5.4% had p16-positive/HPV-negative disease, 44.3% had double-positive disease, and 46.5% had double-negative disease.

The 5-year overall survival (OS) rate was 81.1% for double-positive patients, 40.4% for double-negative patients, 53.2% for p16-negative/HPV-positive patients, and 54.7% for p16-positive/HPV-negative patients. 

The 5-year disease-free survival (DFS) rate was 84.3% for double-positive patients, 60.8% for double-negative patients, 71.1% for p16-negative/HPV-positive patients, and 67.9% for p16-positive/HPV-negative patients. 

In a multivariate analysis with double-positive patients serving as the reference, the OS and DFS were significantly worse for patients with discordant p16 and HPV status. However, double-negative patients had the worst prognosis.

For p16-negative/HPV-positive patients, the adjusted hazard ratio [aHR] for OS was 3.15 (95% CI, 2.50-3.97), and the aHR for DFS was 2.36 (95% CI, 1.87-3.97). 

For p16-positive/HPV-negative patients, the aHR for OS was 2.69 (95% CI, 2.21-3.29), and the aHR for DFS was 1.92 (95% CI, 1.42-2.60). 

For double-negative patients, the aHR for OS was 4.05 (95% CI, 3.59-4.58), and the aHR for DFS was 3.27 (95% CI, 2.84-3.76).

“Our findings indicate that classification of patients with oropharyngeal cancer based on p16-positive immunohistochemistry alone is inadequate in a trial setting and is likely to be insufficient in routine clinical practice, both for predicting prognosis and when selecting treatment,” the researchers wrote. 

“Routine HPV testing alongside p16 evaluation, or at least following a positive result on p16 immunohistochemistry, should be mandated in oropharyngeal cancer clinical trials. It is also recommended in the clinical setting for more accurate counseling on prognosis, and in future circumstances in which treatment de-escalation or intensification are being considered.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Mehanna H, Taberna M, von Buchwald C, et al. Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC): A multicentre, multinational, individual patient data analysis. Lancet Oncol. Published online February 13, 2023. doi:10.1016/S1470-2045(23)00013-X