Characteristics of HPV-Driven Nonoropharyngeal Squamous Cell Carcinomas of the Head and Neck


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In a study reported in the Journal of Clinical Oncology, Chakravarthy et al found that human papillomavirus (HPV)-driven tumors accounted for 4.1% of nonoropharyngeal squamous cell carcinomas of the head and neck. HPV-positive tumors were associated with poorer survival and reduced tumor-infiltrating lymphocyte levels compared with HPV-driven tumors. Tim R. Fenton, PhD, of the University College London Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.

HPV-driven oropharyngeal squamous cell carcinomas are associated with improved prognosis vs HPV-negative disease. HPV DNA is also detectable in nonoropharyngeal squamous cell carcinomas, but its role in pathogenesis and clinical outcomes remains unclear.

The current study used data on HPV status of 520 squamous carcinomas of the head and neck profiled by The Cancer Genome Atlas; DNA-methylation data were used to classify 464 head and neck squamous cell carcinomas, with analyses being integrated with genomic, histopathologic, and survival data.

Study Findings

Overall, HPV-driven tumors accounted for 4.1% of nonoropharyngeal squamous cell carcinomas. HPV-positive head and neck squamous cell carcinomas had highly similar gene expression and DNA-methylation profiles, nonkeratinizing and basaloid histopathologic features, and lack of TP53 or CDKN2A alterations irrespective of anatomic site.

Overall survival was improved among patients with HPV-positive oropharyngeal squamous cell carcinoma vs HPV-positive nonoropharyngeal squamous cell carcinoma (hazard ratio = 0.17, P = .05). Assessment of tumor-infiltrating lymphocyte levels by measuring CD4 (helper/regulatory T lymphocyte) and CD8A/CD8B (cytotoxic T lymphocyte) mRNA levels showed significantly higher levels of mRNA for both (P < .05) in HPV-positive oropharyngeal squamous cell carcinomas vs nonoropharyngeal squamous cell carcinomas. Increased tumor-infiltrating lymphocyte levels were also found in stained sections of HPV-positive oropharyngeal squamous cell carcinomas vs nonoropharyngeal squamous cell carcinomas, as was increased expression of multiple T-cell effector markers.

The investigators concluded: “Our analysis identified a causal role for HPV in transcript-positive [nonoropharyngeal squamous cell carcinomas] throughout the head and neck. Notably, however, HPV-driven [nonoropharyngeal squamous cell carcinomas] display a distinct immune microenvironment and clinical behavior compared with HPV-driven [oropharyngeal squamous cell carcinomas].”

The study was supported by Rosetrees Trust and Cancer Research UK.

Chakravarthy A, et al: J Clin Oncol 34:4132-4141, 2016.



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