HPV16 antibodies as risk factors for oropharyngeal cancer and their association with tumor HPV and smoking status

• Antibodies to the HPV16 proteome were measured in 256 cases of OPC and 250 controls.
• Early gene Abs were detected in the sera of 85% of HPVOPC cases and 4% of controls.
• Seropositivity is strongly associated with OPC risk (OR 249).
• Seropositivity is associated with tumor HPV16 status.

SummaryBackgroundAntibodies (Abs) to the HPV16 proteome increase risk for HPV-associated OPC (HPVOPC). The goal of this study was to investigate the association of a panel of HPV16 Abs with risk for OPC as well as the association of these Abs with tumor HPV and smoking status among patients with OPC.MethodsIgG Abs to the HPV16 antigens E1, E2, E4, E5, E6, E7, L1, L2 were quantified using a programmable ELISA assay. Sera were obtained from 258 OPC patients at diagnosis and 250 healthy controls. HPV16 tumor status was measured by PCR for 137 cases. Multivariable logistic regression was used to calculate odds ratios for the association of HPV16 Abs with risk for OPC.ResultsHPV16 E1, E2, E4, E5, E6, E7 and L1-specific IgG levels were elevated in OPC patients compared to healthy controls (p < 0.05). After multivariable adjustment, Ab positivity for NE2, CE2, E6, and/or E7 was associated with OPC risk (OR [95% CI], 249.1 [99.3–624.9]). Among patients with OPC, Ab positivity for these antigens was associated with tumor HPV status, especially among never or light smokers (OR [95% CI], 6.5 [2.1–20.1] and OR [95% CI], 17.5 [4.0–77.2], respectively).ConclusionsAntibodies to HPV16 proteins are associated with increased risk for HPVOPC. Among patients with OPC, HPV16 Abs are associated with tumor HPV status, in particular among HPV positive patients with no or little smoking history.