JAMA Otol Logo Orlando 2013 AHNS Meeting Location
American Head & Neck Society
Annual Meeting, April 10-11, 2013
JW Marriott Grande Lakes
Orlando, Florida

During the
Combined Otolaryngology Spring Meeting
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Presentation: P042
Topic: Clinical - Gen. Head & Neck Surgery
Type: Poster
Date: Wednesday - Thursday, April 10 - 11, 2013
Session: Designated Poster viewing times
Authors: Shane Gailushas, MD, David Yang, MD, Paul Harari, MD, Gregory Hartig, MD
Institution(s): University of Wisconsin Hospital


 Head and Neck Unknown Primary squamous cell carcinoma (HNUP) accounts for 3-7% of mucosal squamous cell carcinoma of the head and neck. At the University of Wisconsin, persons with an initial diagnosis of HNUP undergo CT/PET fusion imaging, nasopharyngoscopy, and direct laryngoscopy with directed biopsies. If the nodal disease is in level 2, this includes biopsies of the tongue base and ipsilateral tonsillectomy. In many patients, the primary site is identified, but in the remainder, radiation fields are more comprehensive and morbidity is increased.

HPV associated squamous cell carcinoma (HPVSC) of the head and neck shares features with HNUP including small primary site tumors and higher N stage at diagnosis. Approximately 80% of HNUP and near 100% of HPVSC have an oropharyngeal origin. This study evaluates the prevalence of HPVSC in the HNUP population as compared to a group of known oropharyngeal squamous cell cancer (OPSC). This was accomplished by evaluation of p16 immunohistochemistry and high-risk HPV in-situ hybridization (hrHPV) in lymph nodes from both HNUP and OPSC patients. In addition, primary site tissue was also evaluated for p16 and hrHPV positivity in known OPSC patients.


After obtaining IBR approval, our head and neck database was queried for all HNUP and OPSC cases from 1990 to present. These were cross-references with archived pathological tissue blocks for the same period. Of the 97 HNUP patients in the database, 36 had adequate nodal tissue for evaluation. This resulted in 36 HNUP and 121 OPSC cases with tissue for testing. H&E slides were made from each and reviewed by an experience pathologist to confirm the presence and location of SCC within the sample. Next, a tissue microarray consisting of punches from these locations for each sample was created with 3 identical copies. Slides from these arrays were then stained for p16 and confirmatory high-risk HPV in-situ testing ( hrHPV)


Of the 36 HNUP cases, 19 (53%) were positive for p16 with 16 (44%) positive for hrHPV. Of 121 known OPSC cases, 91 (75%) were p16 positive and 70 (57%) were positive for hrHPV. Additionally, OPSC cases with nodal metastasis were tested to determine how p16 and hrHPV positivity in the primary site compared with the nodal site. P16 results correlated in 24/28 (86%) samples with 3 cases positive in primary site but not nodal sites and 1 case the reverse. For hrHPV testing results correlated in 24/28 (86%) cases with 3 negative primary sites with positive nodal sites and 1 case in reverse. For primary site samples p16 and hrHPV correlated in 24/28 (86%) cases. For nodes 26/28 (93%) cases correlated


Approximately half of all HNUP patients in this review were also HPVSC. Routine testing of HNUP nodal samples for HPV can help diagnostic and treatment decision making. Perhaps combined HNUP / HPVSC patients can have radiotherapy fields limited to the oropharynx. Limitations of our study include the retrospective nature of this analysis.

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