ABSTRACT Importance Sinonasal carcinomas are rare but aggressive malignancies. A subset is associated with high‐risk HPV, but risk factors for HPV‐associated sinonasal carcinoma (HPV‐SNC) and HPV‐independent disease remain poorly understood. Objective To evaluate behavioral and clinical risk factors, including sexual history and substance use, and HPV antibody seropositivity in patients with HPV‐SNC and HPV‐independent SNC. Design, Setting, and Participants This multi‐institutional case–case–control study was conducted from 2021 to 2024 at two NCI‐designated cancer centers. Fifty‐two patients with sinonasal carcinoma were enrolled; 37 completed a survey of demographic, clinical, and behavioral factors (24 HPV‐SNC, 13 HPV‐independent SNC) and serology was obtained for 36 (24 HPV‐SNC, 12 HPV‐independent SNC). Control noncancer otolaryngology patients ( n = 148) from a recent prior study were matched 4:1. Exposure Self‐reported history of sexual behaviors, substance use, and medical history via electronic survey; serum testing for antibodies to low‐ and high‐risk HPV E6, E7, E1, E2, and L1 oncoproteins using a multiplex bead‐based assay. Main Outcome and Measure Odds of HPV‐SNC or HPV‐independent SNC diagnosis in relation to risk factors; differences in HPV seropositivity between groups. Results Among the 37 cancer patients who completed the survey, a history of tonsillectomy was significantly associated with reduced odds of HPV‐SNC (OR 0.28, CI 0.09–0.86). No other factors explored (sexual behavior, substance use, or other clinical factors) were associated with HPV‐associated SNC and HPV‐independent SNC. Seroprevalence of anti‐HPV16 E6 was significantly higher among HPV‐associated SNC cases than either controls or HPV‐independent SNC (45.8% vs. 0% and 13.1%), HPV‐16 E6 (18.2% vs. 0% and 4.0%), and HPV‐16 early proteins (16.7% vs. 0% and 0%) than HPV‐independent SNC patients or controls, respectively. Conclusions and Relevance HPV‐SNC exhibits distinct serologic features without clear behavioral risk factors. The protective association of tonsillectomy suggests lymphoid tissue may play a role in HPV‐associated sinonasal oncogenesis. In contrast, the absence of identifiable risk factors for HPV‐independent SNC highlights the need for further etiologic studies.
Tanavde et al. (Thu,) studied this question.