Background There is a paucity of biomarkers to predict failure in human papilloma-virus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) following curative therapy. E6/E7 viral oncoproteins are constitutively expressed in HPV+ tumors and highly immunogenic, resulting in readily detected serum antibodies. The purpose of this study is to determine if serum E6 and E7 antibody levels can potentially serve as a biomarker of recurrence in patients with HPV+OPSCC. Methods We evaluated E6/E7 antibody levels in patients with previously untreated, advanced stage (III, IVa-b), HPV+OPSCC receiving definitive chemoradiation under a uniform protocol from 2003-2010. Baseline and longitudinal serum samples were obtained from our archived repository. E6/E7 serum levels were measured using a glutathione-S-transferase capture ELISA and quantified by approximating the area under the dilution curve, and were analyzed using ANOVA and linear mixed model for longitudinal analysis. Results We compared 22 HPV+OPSCC patients who developed recurrence to 30 patients who remained disease-free. There were no differences in T classification, N classification, disease subsite or smoking status between the groups. In a longitudinal analysis, recurrent patients had significantly higher E6 and E7 serum antibody levels than the non-recurrent patients over the follow-up period (p=0.02 and p=0.002, respectively). Patients who recurred had a lower clearance of E7 antibody than patients who remained disease free (p=0.0016). Conclusion Patients with HPV+OPSCC whose disease recurs have a lower clearance of E6 and E7 antibodies than patients who do not recur. The ratio of E7 antibody at disease recurrence compared to baseline is potentially a clinically significant measurement of disease status in HPV+OPSCC.

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