Dataset Information

P16 status, pathologic and clinical characteristics, biomolecular signature, and long-term outcomes in head and neck squamous cell carcinomas of unknown primary.

ABSTRACT:

Background

The purpose of this study was to report associations between p16 status, clinicopathologic characteristics, and outcomes for head and neck squamous cell carcinoma of unknown primary (CUP).

Methods

Specimens of squamous cell CUP were reanalyzed. Human papillomavirus (HPV) status was determined by p16 stain. A tissue microarray (TMA) was constructed to evaluate biomarkers potentially prognostic in head and neck squamous cell carcinoma (HNSCC).

Results

A majority of the population (n = 26; 74%) was p16 positive (+). Prognostic factors benefiting survival were p16+ status (p < .0001), absence of macroscopic extracapsular extension (ECE; p = .004), younger age (p = .01), and higher grade (p = 0.007). The prognostic implication of worse overall survival (OS) with macroscopic ECE (p = .009) remained significant when limited to patients who were p16+ (p = .002). Exploratory TMA between unknown primary and controls suggested a biomolecular difference between squamous cell CUP and known-primary cancer.

Conclusion

The majority of patients with squamous cell CUP were p16+, indicative of HPV association. P16 staining and ECE seem to be the most prognostic features in squamous cell CUP.

SUBMITTER: Keller LM

PROVIDER: S-EPMC3972378 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Publications

p16 status, pathologic and clinical characteristics, biomolecular signature, and long-term outcomes in head and neck squamous cell carcinomas of unknown primary.

Keller Lanea M LM Galloway Thomas J TJ Holdbrook Thomas T Ruth Karen K Yang Donghua D Dubyk Cara C Flieder Douglas D Lango Miriam N MN Mehra Ranee R Burtness Barbara B Ridge John A JA

Head & neck 20140113 12

<h4>Background</h4>The purpose of this study was to report associations between p16 status, clinicopathologic characteristics, and outcomes for head and neck squamous cell carcinoma of unknown primary (CUP).<h4>Methods</h4>Specimens of squamous cell CUP were reanalyzed. Human papillomavirus (HPV) status was determined by p16 stain. A tissue microarray (TMA) was constructed to evaluate biomarkers potentially prognostic in head and neck squamous cell carcinoma (HNSCC).<h4>Results</h4>A majority of ...[more]

PMID: 24115269

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Project description:A subset of head and neck squamous cell carcinomas present solely as metastatic disease in the neck and are of unknown primary origin (SCCUP). Most primary tumors will ultimately be identified, usually in the oropharynx. In a minority of cases, the primary site remains elusive. Here, we examine the role of ancillary testing, including mutational signature analysis (MSA), to help identify likely primary sites in such cases. Twenty-two cases of SCCUP in the neck, collected over a 10-year period, were classified by morphology and viral status; including human papillomavirus (HPV) testing by p16 immunohistochemistry (IHC) and RT-qPCR, as well as Epstein-Barr virus (EBV) testing by EBER-ISH. CD5 and c-KIT (CD117) IHC was done to evaluate for possible thymic origin in all virus-negative cases. Whole exome sequencing, followed by MSA, was used to identify UV signature mutations indicative of cutaneous origin. HPV was identified in 12 of 22 tumors (54.5%), favoring an oropharyngeal origin, and closely associated with nonkeratinizing tumor morphology (Fisher's exact test; p = 0.0002). One tumor with indeterminant morphology had discordant HPV and p16 status (p16+/HPV-). All tumors were EBV-negative. Diffuse expression of CD5 and c-KIT was identified in 1 of 10 virus-negative SCCUPs (10%), suggesting a possible ectopic thymic origin rather than a metastasis. A UV mutational signature, indicating cutaneous origin, was identified in 1 of 10 (10%) virus-negative SCCUPs. A cutaneous auricular primary emerged 3 months after treatment in this patient. Primary tumors became clinically apparent in 2 others (1 hypopharynx, 1 hypopharynx/larynx). Thus, after follow-up, 6 tumors remained unclassifiable as to the possible site of origin (27%). Most SCCUPs of the neck in our series were HPV-associated and thus likely of oropharyngeal origin. UV signature mutation analysis and additional IHC for CD5 and c-KIT for possible thymic origin may aid in further classifying virus-negative unknown primaries. Close clinical inspection of hypopharyngeal mucosa may also be helpful, as a subset of primary tumors later emerged at this site.