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

Abstract

Background To report associations between p16 status, clinicopathologic characteristics, and outcomes for unknown primary head and neck squamous cell carcinoma (SCCUPS). Methods Specimens of SCCUPS were re-analyzed. HPV status was determined by p16 stain. A tissue microarray (TMA) was constructed to evaluate biomarkers potentially prognostic in HNSCC. Results A majority of the population (n = 26, 74%) was p16+. Prognostic factors benefitting survival were p16+ status (p < 0.0001), absence of macroscopic extracapsular extension [ECE] (p = 0.004), younger age (p = 0.01), and higher grade (p = 0.007). The prognostic implication of worse OS with macroscopic ECE (p = 0.009) remained significant when limited to p16+ patients (p=0.002). Exploratory TMA between unknown primary and controls suggested a biomolecular difference between SCCUPS and known-primary cancer. Conclusions The majority of SCCUPS patients were p16+, indicative of HPV association. p16 staining and ECE appear to be the most prognostic features in SCCUPS.

Impact of the 8th edition of the UICC TNM classification on staging and survival in patients with neck metastases of unknown primary tumor

“…In our cohort the prevalence of HPV-positivity in patients with CUP was with 30% clearly lower compared to 70% in patients with a detected PT but in line with the literature (18-40%) [54][55][56][57]. Only Keller et al [58] reported with 74% (26/39) on a higher prevalence of p16 expression in lymph node metastases in patients with CUP. Besides the epidemiologic impact of HPV-positivity in OPSCC the HPV-status of a tumor also plays an important prognostic role.…”

Patterns of Failure in Patients With Head and Neck Carcinoma of Unknown Primary Treated With Radiation Therapy

“…Finally, similar to oropharyngeal cancers, recent data have implicated human-papillomavirus (HPV) association as a major prognostic factor for disease-free and overall survival in patients with HNCUP. [28][29][30][31] Irradiating the oropharynx alone may be sufficient for a patient with a HPV-associated cancer and no involved lymph nodes below level II. However, any suspicion of nasopharyngeal primary tumors warrants coverage of the nasopharynx, as recent data have associated HPV-positive nasopharyngeal carcinomas with a significantly worse prognosis compared with their HPV-negative counterparts.…”

Accuracy of Diagnostic Methods for Detection of Head and Neck Primary Origin in Metastatic Neck Mass

“…A meta-analysis published in 2007 regarding non-oropharyngeal HNSCC shows congruent results [68]. However, most of the published literature agrees that HPV/p16 is a positive prognostic indicator for HNCUP [69,70].…”

“…The current paradigm for the indications for postoperative chemo-irradiation (R1, pN3b) originates from the pre-HPV-stratification era [104,105]. Keller et al [70] have conducted an analysis of clinicopathological data, including p16 and extracapsular extension (ECE), in HNCUP and could demonstrate a very similar prognosis in patients with or without ECE, even without chemotherapy, but the patient numbers in this analysis where very limited and so no safe conclusions can be drawn. A treatment-deescalation for HPV/p16 nonsmokers could be imaginable, either through omitting chemotherapy or even by using chemotherapy in order to reduce RT-dose, following the paradigm of current HNSCC trials [102].…”