Behavioral Risk Factors and Seroprevalence for Human Papillomavirus in Sinonasal Carcinoma: A Multi-Institutional Case-Control Study.

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.

Duke Scholars

Author David W Jang Rhinology and Skull Base Surgery

Author Ralph Abi Hachem Rhinology and Skull Base Surgery