Survival benefit for HPV+ OPSCC patients with dominant serum IgA over IgG antibodies against HPV16 L1

Abstract

Abstract Background Although the therapy response of HPV-positive oropharyngeal carcinomas (OPSCC) is known to be significantly better compared to HPV-negative tumors, about 25% of them will have a recurrence within the first 5 years after therapy. Therefore, it is of great scientific interest to find relevant biomarkers to identify subgroups with a poorer prognosis. In this prospective observational study, we examine for the first time the behavior of HPV-L1 antibody subclasses IgA, IgG, and IgM in HPV-positive OPSCC patients under therapy. Material and Methods The study cohort included patients with HPV-positive OPSCCs from the Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Graz. Serum samples were collected before and during tumor-specific therapy and follow-up. They were analyzed for the presence of HPV-L1 antibody (AB) subclasses IgA, IgM, and IgG using an HPV-L1-specific immuno-assay. In addition, a PCR-based HPV-DNA detection and subtyping from the tumor tissue was performed. Statistical analysis included Chi2- and Kruskal-Wallis-H-Test for significance testing. Correlation between two ordinal sizes has been tested using Spearmen-Rho. Results Altogether, 34 patients with a mean age of 63.5 years and a mean follow-up of 55 months were included. The most common L1-AB-subclass pattern was characterized by IgG > > IgA > IgM (13 cases) without significant fluctuation. The second most common pattern was IgG > IgA > IgM (6 cases). In 5 cases an antibody pattern of IgA > IgG > IgM while in 4 cases IgG = IgA > IgM was seen. Three out of 4 recurrences had previously shown an increase in IgG antibodies. Patients with excessive IgG levels tended to have higher tumor stages. IgA dominance at diagnosis was associated with better disease-free survival. Conclusions In this prospective longitudinal observational study, we show for the first time the behavior of HPV-L1 antibody subclasses IgA, IgG, and IGM in HPV-positive OPSCC patients under therapy. IgA dominance at diagnosis was associated with better disease-free survival, whereas a higher IgG/IgA ratio correlated with higher tumor stages. In three recurrent tumors, an increase in the IgG AB level could be shown beforehand. HPV-L1 AB-subclass detection might be of use for future risk stratification in HPV-pos. OPSCC patients.