The Prognostic Role of Baseline Eosinophils in HPV-Related Cancers: a Multi-institutional Analysis of Anal SCC and OPC Patients Treated with Radical CT-RT

Background and Aim: Anal squamous cell carcinoma (SCC) and oropharyngeal cancer (OPC) are rare tumors associated with HPV infection. Bioumoral predictors of response to chemoradiation (CT-RT) are lacking in these settings. With the aim to find new biomarkers, we investigated the role of eosinophils in both HPV-positive anal SCC and HPV-related oropharyngeal cancer (OPC). Methods: We retrieved clinical and laboratory data of patients with HPV-positive anal SCC treated with CT-RT in 5 institutions, and patients with locally advanced OPC SCC treated with CT-RT in 2 institutions. We examined the association between baseline eosinophil count (the best cutoff has been evaluated by ROC curve analysis: 100 × 10^9/L) and disease-free survival (DFS). Unadjusted and adjusted hazard ratios by baseline characteristics were calculated using the Cox proportional hazards model. Results: Three hundred four patients with HPV-positive anal SCCs and 168 patients with OPCs (122 HPV-positive, 46 HPV-negative diseases) were analyzed. In anal SCC, low eosinophil count (< 100 × 10^9/L) correlates to a better DFS (HR = 0.59; p = 0.0392); likewise, in HPV-positive OPC, low eosinophil count correlates to a better DFS (HR = 0.50; p = 0.0428). In HPV-negative OPC, low eosinophil count confers worse DFS compared to high eosinophil count (HR = 3.53; p = 0.0098). After adjustment for age and sex, eosinophils were confirmed to be independent prognostic factors for DFS (HR = 4.55; p = 0.0139). Conclusion: Eosinophil count could be used as a prognostic factor in anal HPV-positive SCC. The worse prognosis showed in HPV-positive patients with high eosinophil count is likely to derive from an unfavorable interaction between the HPV-induced immunomodulation and eosinophils, which may hamper the curative effect of RT.