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p16 expression predicted outcomes in non-OPSCC

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November 3, 2014

Patients with p16-positive non-oropharyngeal squamous cell carcinoma experienced better outcomes than those with p16-negative tumors, according to an analysis of three prospective clinical trials.

Previous studies showed p16 protein expression — a surrogate marker for oncogenic HPV infection — is a prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC). However, the prevalence and significance of p16 protein expression in non-OPSCC — which includes cancers of the larynx, hypopharynx and oral cavity — has not been established, according to background information provided by researchers.

In the current study, researchers tested tumors of 356 patients with non-OSCC tumors who were enrolled in the RTOG 0129, 0234 and 0522 studies. They determined p16 expression for 322 (90.4%) of those tumors.

Overall, 62 of the 322 tumors (19.3%) with confirmed p16 status tested positive. The highest rates of p16 positivity were observed in cancers of the oral cavity (26.3%), followed by cancers of the larynx (17.1%) and hypopharynx (16.4%).

Researchers determined patients with p16-positive tumors experienced significantly longer PFS (HR=0.63; 95% CI, 0.42-0.95) and OS (HR=0.56; 95% CI, 0.35-0.89) than those with p16-negative tumors.

Results also showed patients with p16-positive OPSCC demonstrated superior PFS and OS compared with those who had p16-positive non-OPSCC. However, outcomes among those with p16-negative OPSCC and p16-negative non-OPSCC were similar, according to researchers.

“Similar to results in patients with OPSCC, patients with p16-negative non-OPSCC have worse outcomes than patients with p16-positive non-OPSCC, and HPV may also have a role in outcome in a subset of non-OPSCC,” the researchers concluded. “However, further development of a p16 immunohistochemistry scoring system in non-OPSCC and improvement of HPV detection methods are warranted before broad application in the clinical setting.”

Disclosure: The researchers report honoraria from Bristol-Myers Squibb and Merck, as well as other remuneration from Roche.

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Ranee Mehra

Ranee Mehra

This paper describes a comprehensive analysis of HPV status and p16 expression among patients from three cooperative group studies for patients with squamous cell head and neck cancers from a variety of primary site locations who all underwent chemotherapy and radiation as part of their definitive therapy. It is a retrospective analysis and the characteristics of the three studies varied with regard to which systemic agents were used, as well as the use of the EGFR inhibitor cetuximab (Erbitux, Imclone). Nonetheless, it establishes that p16 is not a surrogate marker for HPV in non-oropharyngeal squamous cell head and neck cancers. Although this immunohistochemistry assay is often incorporated in the diagnostic evaluation of a newly diagnosed head and neck cancers, it is clear from this report that it should not influence decision-making for a non-oropharynx primary site. This report also is thought provoking with regard to the biological and clinical characteristics of the subset of patients who had p16-positive, HPV-negative, non-oropharyngeal primary malignancies. Future research is needed to determine whether we can clearly state that these are not viral-associated cancers, and also to further understand the function of p16 in this subset of malignancies.

Ranee Mehra, MD
HemOnc Today Editorial Board Member
Fox Chase Cancer Center

Disclosure: Mehra reports no relevant financial disclosures.