Abstract 770: High-grade neuroendocrine carcinoma of the oropharynx: A rare entity with prognosis unaffected by HPV
Authors: Sousa Luana , Lazar Felippe , Torman Danice , Li Kaiyi , Sikora Andrew , Moreno Amy , Hanna Ehab , Phan Jack , Glisson Bonnie , Bell Diana , Ferrarotto Renata 
Published: July 2021

Abstract
Background: Human Papilloma Virus (HPV) infection is associated with a better prognosis in oropharynx squamous cell carcinomas. Neuroendocrine carcinoma (NEC) of the oropharynx is a rare variant that can be associated with HPV infection, however little is known regarding clinical behavior and the impact of HPV infection on its prognosis. This study aims to evaluate clinical and pathologic features of oropharyngeal high-grade NEC and to investigate the prognostic value of HPV and smoking in this rare histological subtype. Methods: Patients with high-grade NEC from oropharynx were identified through electronic medical records queries from 1997 to 2020. A cohort of 27 patients with sufficient pathological and clinical data were included in the analysis. Neuroendocrine differentiation was confirmed by immunoreactivity for synaptophysin, chromogranin and/or CD56. P16 immunohistochemistry staining or HPV in situ hybridization or polymerase chain reaction were performed in all patients' samples. Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. The log-rank test was used to assess difference in survival between groups. Results: Of 27 patients, 25 were male and 10 had a heavy smoking history (≥10-pack-years). P16 staining was positive in 24 (89%) samples and HPV was confirmed in 15 (62.5%). Most patients (22/27; 81.5%) presented with locoregional disease, 8 (35%) received induction chemotherapy, and 18 of 23 (78%) achieved a complete response after definitive therapy (surgery and/or radiation); among them, 7 (30%) recurred. Most recurrences were distant and common sites of metastasis was liver (56%), bone (56%) and lymph nodes (50%). In the palliative setting, 85% of patients received platinum-based chemotherapy and preferred combined agents were etoposide (6/14) and docetaxel (5/14). The overall response rate to first- and second-line systemic therapy were 50% and 0%, respectively. The median DFS for those patients who achieved a complete response to definitive therapy was 61.0 months (95% CI 13.0-NA) and 1- and 2-year DFS rates were 73.3% and 56.4%, respectively. The median OS was 28.8 months (95%CI 14.3-NA) for the overall population. Metastasis at diagnosis was associated with lower median survival (9.5 versus 62.0 months, p= 0.016). We have not found differences in median OS according to HPV status(positive 28.9 versus negative 28.8 months, p= 0.93) or smoking exposure (≥10pack/year 47.2 versus &lt;10pack/year 14.3 months, p= 0.8). Conclusions: Distinct from oropharynx squamous cell carcinoma, HPV status is not an independent prognostic factor for high-grade NEC of the oropharynx. Although high-grade NEC is usually associated with a dismal prognosis, most patients with loco-regional disease were cured, suggesting primary disease site has biologic implications. This represents the largest case series of oropharyngeal high-grade NEC.
Citation Format: Luana Sousa, Felippe Lazar, Danice Torman, Kaiyi Li, Andrew Sikora, Amy Moreno, Ehab Hanna, Jack Phan, Bonnie Glisson, Diana Bell, Renata Ferrarotto. High-grade neuroendocrine carcinoma of the oropharynx: A rare entity with prognosis unaffected by HPV [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 770.