Abstract A24: Multitiered assessment of the incidence and demographics of patients with multiple human papillomavirus-mediated head and neck cancers
Authors: Strober William , Wood Burton , Shishido Sachie , Lewis James , Kuhs Krystle , Ferris Robert L. , Faden Daniel L. 
Published: September 2020

Abstract
Human papillomavirus (HPV)-mediated head and neck squamous cell carcinoma (HNSCC) (HPVmHNSCC) is increasing in incidence in the US. Treatment paradigms for early-stage HPVmHNSCC are shifting toward transoral surgical resection and minimization of primary and adjuvant radiation to decrease treatment-related morbidity. Reports have emerged citing a risk of synchronous or metachronous (multiple) HPVmHNSCC. The incidence, patient demographics, and implications for treatment decision making of this emerging clinical entity are poorly understood. We performed a multitiered assessment of patients with multiple HPVmHNSCC, including: 1. systematic review of the literature, 2. query of the 2017 Surveillance, Epidemiology and End Results (SEER) database, and 3. institutional level reporting at two high-volume academic centers. 501 journal entries were identified using search terms in PubMed, Embase, and Web of Science. 13 articles met inclusion criteria, amounting to 50 patients. The pooled incidence of multiple HPVmHNSCC was 3.31% of all HPVmHNSCC. Query of the SEER database from 2013-2015, the years in which HPV data are available, revealed 33 (0.52%) patients with multiple HPVmHNSCC and 62 (0.98%) patients who had a second primary tumor that was either HPVmHNSCC or had unknown HPV status. 82% were synchronous. Synchronous tumors were more likely to have the same grade compared to metachronous tumors (p=0.028). The second diagnosed tumor from a pair tended to be smaller (1.7cm vs 2.3cm) and was 2.7x more likely to be found on the contralateral side (p=0.026). 62% of multiple HPVmHNSCC occurred in the tonsil, which was statistically increased compared to HPVmHNSCC overall (p=0.034). For patients with multiple HPVmHNSCC, the median age of diagnosis, sex, ethnicity, and tumor grade were not different from HPVmHNSCC patients overall. 18 patients with multiple HPVmHNSCC were identified at two high-volume academic centers from 2000-2017 (1.33% of HPVmHNSCC cases). The incidence increased over time, paralleling the overall incidence of HPVmHNSCC. Demographic data from multiple HPVmHNSCC were not statistically different from the HPVmHNSCC population. Based on SEER data, pooled incidence rates from systematic literature review, and institutional data, the estimated incidence of multiple HPVmHNSCC is 0.52-3.31%. This likely underestimates the true incidence due to biases in detection. For example, radiation or surgery to the bilateral oropharynx likely eradicates second primary tumors prior to detection. While second primaries are most likely to be found synchronously, on the contralateral side, and in the tonsil, these data should be interpreted with caution considering a discovery bias. In light of emerging treatment schemes focused on deintensification, including unilateral surgery and radiation protocols and omission of adjuvant radiation in early-stage tumors, prospective studies are needed to better understand the incidence of multiple HPVmHNSCC tumors and how this may affect treatment decision making.
Citation Format: William Strober, Burton Wood, Sachie Shishido, James Lewis, Krystle Kuhs, Robert L. Ferris, Daniel L. Faden. Multitiered assessment of the incidence and demographics of patients with multiple human papillomavirus-mediated head and neck cancers [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A24.