Abstract A136: p16INK4a status of primary tumor modulates local immune response in vulvar squamous cell carcinoma

Background: The p16INK4a is not a surrogate marker for high-risk human papilloma virus genotypes (hr)HPV-DNA) and was suggested to indicate better prognosis of vulvar squamous carcinoma (vSCC). Our recent study confirmed substantial mismatch between p16ink4a and (hr)HPV-status as well as prognostic significance exclusively for p16INK4a-overexpression in cohort of 85 patients. Aim: To compare the infiltration of tumor infiltrating lymphocytes (TILs) and to assess their prognostic significance in cases having tumors with opposed p16INK4a and (hr)HPV-status. Methods: TILs (CD8+, CD4+, FOXP3+, CD68+, CD56+ and GzB+ cells) were calculated in 85 vSCCs with previously defined p16INK4a and (hr)HPV-status. Number of intraepithelial (IE) TIL-subtypes were compared between tumors with different p16INK4a and (hr)HPV-status separately. Survival analyses included the Kaplan-Meier method, log-rank test and Cox proportional hazards model. Results: p16INK4a-negative tumors were infiltrated more intensely by CD8+, CD4+ and GZB+ cells than p16INK4a-positive vSCCs (p = 0.032, p = 0.016 and p = 0.007 respectively). (hr)HPV-status did not impact the infiltration of TILs. Median follow up was 89.20 months (range 1.7-189.5). High (IE)CD4+ infiltrates were prognostic in general cohort and in p16INK4a-positive cases (p = 0.032 and p = 0.039 respectively). High (IE)CD56+ infiltrates were correlated with prognosis in p16INK4a-positive and (hr)HPV-positive cases (p = 0.013 and p = 0.0458 respectively) while high (IE)CD68+ infiltrates were inversely correlated with survival in cases with p16INK4a-negative and (hr)HPV-negative tumors (p = 0.018 and p = 0.0441 respectively). Conclusion: p16INK4a-status modulates local immune surveillance as represented by TILs. Immunologic effects contributing to clinical outcome might depend on p16INK4a-overexpression. Citation Format: Jacek J. Sznurkowski, Anton Zawrocki. p16 INK4a status of primary tumor modulates local immune response in vulvar squamous cell carcinoma [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A136.