Antibody Responses to HPV Infection in Adult-Onset and Juvenile-Onset Recurrent Respiratory Papillomatosis

Introduction: The HPV subtypes 6 and 11 are understood to cause recurrent respiratory papillomatosis (RRP), similarly to how high-risk HPV subtypes—including 16, 18, 31, and 33—lead to HPV-related oropharyngeal cancer (HPV-OPC). Given the similarity in viral etiology of these diseases, examining HPV subtype exposure, seropositivity, and/or immune clearance may explain differential disease presentations.

Methods: Adult-onset RRP (AORRP; n=43), juvenile-onset RRP (JORRP; n=22), HPV-OPC (n=125), and control (n=139) patients were recruited from otolaryngology clinics of a single tertiary care center from 2013 to 2021. Serum was collected and analyzed for antibodies against HPV L1 capsid protein and E1, E2, E4, E6, and E7 early oncoproteins for HPV types 6, 11, 16, 18, 31, 33, 35, 45, 52, and 58. Non-control cohorts were matched by decade of age, sex, and race to the control group. For each experimental group, seropositivity was compared against the control cohort via unadjusted logistic regression.

Results: JORRP participants were significantly more likely to be seropositive to HPV6L1 (OR [95% CI]: 3.46 [1.35 – 8.84]; p=0.01) and HPV11L1 (3.59 [1.27 – 10.12]; p=0.02) relative to control patients. HPV-OPC patients were more likely to be seropositive to antigens including HPV35E7 (41.69 [5.58 – 311.26]; p< 0.001), HPV16E6 (36.79 [11.11 – 121.80]; p< 0.001), and HPV33E6 (20.69 [4.82 – 88.79]; p< 0.001). No HPV antigens were significantly different between AORRP and control patients.

Conclusions: We validate the known association of low-risk (HPV6, HPV11) and high-risk (HPV16, HPV18, HPV31, HPV33) HPV subtypes with JORRP and HPV-OPC, respectively. HPV antibody profiles are similar between AORRP and control patients, suggesting that poor immune-mediated clearance, not HPV serotype-specific exposure, may be key in AORRP pathogenesis.