p16 Not a Prognostic Marker for Hypopharyngeal Squamous Cell Carcinoma

Departments of Radiation Oncology, University of Virginia, Charlottesville, VA 22908, USA.
Archives of otolaryngology--head & neck surgery (Impact Factor: 2.33). 06/2012; 138(6):556-61. DOI: 10.1001/archoto.2012.950
Source: PubMed


To investigate the prognostic significance of p16 in patients with hypopharyngeal squamous cell carcinoma (HPSCC) and to evaluate the relationship between p16 and human papillomavirus (HPV). Unlike in oropharyngeal SCC (OPSCC), the prognostic significance of p16 in HPSCC and its association with HPV is unclear.
Retrospective medical chart review.
University tertiary referral center.
A total of 27 patients with HPSCC treated with definitive radiation therapy between 2002 and 2011 whose tissue was available for immunohistochemical analysis.
Twenty-two patients were treated with chemoradiation, and 5 with radiation alone. All tumor biopsy specimens were analyzed for p16 and, when sufficient tissue was available, for HPV DNA.
Overall survival (OS), locoregional control (LRC), disease-free survival (DFS), and laryngoesophageal dysfunction-free survival (LEDFS) were analyzed according to p16 status.
Findings for p16 were positive in 9 tumors and negative in 18 tumors. Median follow-up was 29.3 months. There was no significant difference in OS, LRC, DFS, or LEDFS for patients with p16-positive vs p16-negative tumors. Only 1 of the 19 tumors tested for HPV was found to be HPV positive. When used as a test for HPV, p16 had a positive predictive value of 17%.
In contrast to OPSCC, p16 expression in patients with HPSCC had a low positive predictive value for HPV and did not predict improved OS, LRC, DFS, or LEDFS. Thus, for HPSCC, p16 is not a prognostic biomarker. Caution must be taken when extrapolating the prognostic significance of p16 in patients with OPSCC to patients with head and neck SCC of other subsites.

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    ABSTRACT: To assess the interaction of HPV/p16 status and therapy rendered in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx. Forty-seven consecutive patients receiving definitive treatment between 2009 and 2011 for locally advanced larynx or hypopharynx cancer with high-risk HPV and/or p16 testing performed were identified and retrospectively investigated. Overall survival (OS), disease-free survival (DFS), and local recurrence-free survival (LRFS) were assessed. Of 47 evaluable patients, there were 38 (81%) with laryngeal and 9 (19%) with hypopharyngeal tumors, 13 (28%) of which were found to be either HPV or p16 positive. At a median follow-up of 24months, comparing HPV/p16+ versus HPV/p16- patients, there was no difference in OS, DFS, or LRFS. There was an improvement in 2-year DFS (60% vs 100%, P=.03) and LRFS (80% vs 100%, P=.08), in HPV/p16+ patients treated with chemo/RT versus surgery. There was an improvement in 2-year DFS (100% vs 68%, P=.04) and LRFS (100% vs 72%, P=.05) in HPV/p16+ versus HPV/p16- patients who received chemo/RT. Patients with HPV/p16+ tumors fared more favorably with chemo/RT than up-front surgery, with improvements in DFS and LRFS. In patients treated with the intent of organ preservation therapy, HPV/p16+ patients had no observed treatment failures. HPV/p16 status should be taken into account when considering organ preservation for locally advanced larynx and hypopharynx cancers.
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