Challenges in Establishing the Diagnosis of Human Papillomavirus-Related Oropharyngeal Carcinoma

Objectives/Hypothesis: To describe initial presentations and idiosyncrasies in establishing the diagnosis for human papillomavirus-related (HPV+) compared to HPV-unrelated (HPV-) oropharyngeal carcinoma (OPC). Study Design: A single institution retrospective series derived from an institutional prospectively compiled database supplemented by chart review. Methods: We reviewed consecutive OPC patients referred to an academic tertiary cancer center from 2009 to 2011. HPV status was evaluated by p16 staining. Signs/symptoms and procedures to establish diagnosis were recorded independently by two abstractors blinded to the HPV status during data retrieval. Initial presentations (signs/symptoms), interval, and the procedures to establish the diagnosis were compared between HPV+ and HPV- OPC. Results: The most common initial presentation was an asymptomatic nodal mass for HPV+ patients (n = 208; 69% vs. 29%, P<.001) in contrast to dysphagia/odynophagia for HPV (n=96; 34% vs. 63%, P<.001). Protracted interval (>12 months) from onset of signs/symptoms to diagnosis was observed in 18 (9%) HPV+ versus three (3%) HPV patients (P=.058). More HPV+ patients required repeated (>= 2) biopsy procedures (56% vs. 10%, P<.001). Misattribution to other disease occurred in eight (4%) HPV+ patients (seven were mistaken as having a branchial cleft cyst when there were cystic lymph nodes and one as having a lymphoma) compared to none in HPV-. Conclusions: About two-thirds of HPV patients present with an asymptomatic neck mass and often require multiple biopsy procedures to establish the diagnosis. Idiosyncrasies in appreciating the diagnostic setting (cystic lymph node, misattribution to other entities, or submucosal location of the tumor) or patient-related factors could delay the diagnosis of HPV+ OPC,