Pre-diagnostic dynamic HPV16 IgG seropositivity and risk of oropharyngeal cancer

Objective The aim of this study was to determine the association of HPV16 antibodies (Abs) and oropharyngeal cancer (OPC) risk in sera obtained prior to clinical diagnosis. Methods We identified 92 participants with incident OPC and 460 matched controls from the Janus Serum Bank Cohort in Norway. Archived tumor specimens were requested for a subset of the cases. Serum samples were collected from cases, on average, 9.3 years before diagnosis (range, 0.1–14.9 years). Ten cases had serum samples from multiple time points. IgG seropositivity to 8 HPV16 antigens was determined, and a logistic regression classifier of a panel of all early-antigen (EA) Abs for the predictive diagnosis of OPC was applied. Results HPV16 EA seropositivity was present in 25.0% of patients with OPC and 7.6% of controls (odds ratio (OR), 4.1; 95% CI, 2.3–7.2, p < 0.0001). Abs to E2 were strongly associated with cases 0–2 years pre- diagnosis (OR, 150.1; 95% CI, 27.4–1040.0, p < 0.0001), and the probability of seropositivity was inversely associated with time to diagnosis (OR, 0.7 per additional year; 95% CI, 0.6–0.9, p = 0.0002). Abs to E2 were also strongly associated with tumor HPV status (OR, 35.6; 95% CI, 8.7–200.0, p < 0.0001). A positive score on the binary classifier was associated with an overall OR of 15.8 (95% CI, 5.6–53.4) compared with controls (p < 0.05), and was strongly associated with tumor HPV status (OR, 27.4; 95% CI, 8.6–99.6, p < 0.001). Conclusions HPV16 Abs are detectable years prior to diagnosis of OPC, and the probability of seropositivity increases closer to diagnosis.