Abstract 2265: HPV16 serostatus and risk of oropharyngeal carcinoma
Authors: Dahlstrom Kristina R. , Anderson Karen S. , Field Matthew S. , Chowell Diego , Li Guojun , Sturgis Erich M. 
Published: July 2017

Background: The current epidemic of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) urgently demands a screening strategy for this disease. Antibodies to HPV type 16 (HPV16) early (E) antigens have been detected in patients with HPV16-related OPC, and are potential biomarkers of HPV-related malignancies. The goal of this study was to evaluate the diagnostic accuracy of a panel of antibodies to HPV16 E antigens.

Methods: This was a case-control study that included 378 patients with OPC, 153 patients with non-oropharyngeal head and neck cancer, and 782 healthy control subjects. All patients had newly diagnosed, previously untreated disease and were matched with controls by age and sex. Tumor HPV status was determined by p16 immunohistochemistry. IgG antibodies to the HPV16 antigens E1, E4, E5, E6, E7, and the N-terminal and C-terminal fragments of E2 (NE2, CE2) were quantified using a custom multiplexed bead array assay. A binary logistic regression classifier based on the combined relative light units of all E antigens on ELISA was pre-defined and applied to the dataset. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using logistic regression analysis.

Results: Of the 378 patients with OPC, 348 had p16-positive OPC. Using the single cutoff values, the frequency of seropositivity for the individual antigens vs. controls was E1 (74% vs 7%); CE2 (68% vs 1%); E6 (42% vs 1%); and E7 (64% vs 1%)(Table 1). Positivity for the binary classifier was associated with an OR of 453 (95% CI, 199-1030) for p16-positive OPC, with a sensitivity of 83% and a specificity of 99% (Table 1).

Conclusions: HPV-specific IgG antibodies to multiple early antigens are detected at the time of diagnosis of HPV-related OPC. A multiparametric algorithm improves the specificity of detection of cases over single antibodies and are potential biomarkers for HPV-associated malignancies that may be advantageous for risk stratification in future screening trials.

Table 1.A blinded study of HPV16 serology of patients with p16-positive OPC (n=348) and controls (n=782).Controlsp16+ OPCN+ (%)N+ (%)OR (95% CI)aSensitivitySpecificityPPVNPVAUCE152 (6.7)256 (73.6)43 (28-67)74938389.84NE214 (1.8)128 (36.8)43 (20-90)37989078.68CE27 (0.9)235 (67.5)290 (114-741)68999787.83E414 (1.8)110 (31.6)27 (13-54)32988976.65E548 (6.1)37 (10.6)2 (1-4)11944470.52E69 (1.2)146 (42.0)80 (34-187)42999479.70E711 (1.4)224 (64.4)106 (54-208)64999586.82Classifier8 (1.0)288 (82.8)453 (199-1030)83999793.91aAdjusted for sex, smoking, and alcohol status (never vs. former vs. current)OR: odds ratio; CI: confidence interval; PPV: Positive Predictive Value; NPV: Negative Predictive Value; AUC: Area Under the Curve

Citation Format: Kristina R. Dahlstrom, Karen S. Anderson, Matthew S. Field, Diego Chowell, Guojun Li, Erich M. Sturgis. HPV16 serostatus and risk of oropharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2265. doi:10.1158/1538-7445.AM2017-2265