<h3>Purpose/Objective(s)</h3> Adenosquamous carcinoma of the head and neck (ASC-HN) is a rare and aggressive variant of squamous cell carcinoma (SCC). Limited data suggests inferior outcomes compared to conventional SCC. We report one of the largest single institutional experiences of this disease in patients treated definitively to further elucidate oncologic outcomes. <h3>Materials/Methods</h3> Patients with non-metastatic ASC-HN treated definitively between 2003 and 2021 were identified retrospectively from an IRB approved database with histology verified by head and neck pathologists. All tumors of the oropharynx were tested for p16 and/or HPV to document HPV associated disease. For non-oropharyngeal lesions, a designation of HPV positivity required the presence of HPV DNA/RNA per CISH. Actuarial analyses were performed for PFS and OS. <h3>Results</h3> 29 patients with ASC-HN (72.4% male, 93.1% Caucasian) with median age of 66 (range 34-91) and a median follow up of 33 months (range 6.6-126.7) were identified. The most common primary tumor sites were: oropharynx (27.6%), oral cavity (20.7%), nasal cavity (17.2%), and larynx (17.2%). 3 patients had primaries in the hypopharynx, nasopharynx and parotid gland respectively. 11 patients (37.9%) were HPV positive of whom 8 had oropharyngeal primaries. The majority (n=23, 79.3%) were treated with primary surgery of whom 19 (82.6%) received adjuvant radiation (RT) to a median dose of 60 Gy (range 36-70 Gy) with 7 receiving concurrent chemotherapy. 6 patients were treated with definitive RT to a median dose of 70 Gy with two receiving concurrent chemotherapy. There were 10 recurrences (34.5%) which occurred at a median of 14.3 months (range 5.4-28) after diagnosis including 8 loco-regional and 2 distant recurrences. Recurrences were documented in patients with primary salivary gland, oral cavity, laryngeal, hypo-pharyngeal, and oropharyngeal tumors. 3 of the 10 recurrences were in patients with HPV positive disease. Among the 6 patients treated with definitive radiation or chemo-radiation no failures were observed. 9 patients (31%) were deceased at the time of analysis. Overall, 3-year PFS and OS were 54.2% and 72.9%, respectively. 3-year PFS and OS were 45.6% and 69.6% for primary surgery and 83.3% and 83.3% in the definitive RT group. 3-year PFS was 50% and 75% for HPV negative and positive patients respectively. <h3>Conclusion</h3> In our single institutional experience of 29 patients with adenosquamous carcinoma of the head and neck there was a 34.5% recurrence rate. Loco-regional recurrence was the primary mode of failure.
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