Research Papers:

Local immune response depends on p16INK4a status of primary tumor in vulvar squamous cell carcinoma

Jacek J. Sznurkowski _, Anton Żawrocki and Wojciech Biernat

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Oncotarget. 2017; 8:46204-46210. https://doi.org/10.18632/oncotarget.17581

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Jacek J. Sznurkowski1, Anton Żawrocki2 and Wojciech Biernat2

1Department of Oncological Surgery, The Medical University, Gdańsk, Poland

2Department of Pathology, The Medical University, Gdańsk, Poland

Correspondence to:

Jacek J. Sznurkowski, email: [email protected]

Keywords: vulvar SCC, p16, TILs, TAMs, prognosis

Received: December 29, 2016     Accepted: April 04, 2017     Published: May 03, 2017


Background: The p16Ink4a is not a surrogate marker for high-risk human papilloma virus (HPV) genotypes but indicates better prognosis in vulvar squamous cell carcinoma patients. Our recent study confirmed substantial mismatch between p16Ink4a and high-risk HPV-status as well as revealed that p16Ink4a-overexpression itself is an independent prognostic factor for vulvar cancer.

Aim: To determine significance of the tumor infiltrating immune cells and p16Ink4a–status for better outcome of patients with vulvar cancer.

Methods: Intraepithelial tumor infiltrating lymphocytes: CD8+, CD4+, FOXP3+, CD56+, tumor associated macrophages: CD68+, and GZB+ cells were calculated in 85 vulvar squamous cell carcinomas with previously defined p16Ink4a and high-risk HPV-status. Number of intraepithelial CD8+, CD4+, FOXP3+, CD56+, CD68+ and GZB+ cells were compared between tumors with different p16INK4a status and overlapping high-risk HPV-status separately. Survival analyses included the Kaplan–Meier method, log-rank test and Cox proportional hazards model.

Results: p16Ink4a-negative tumors were more infiltrated by intraepithelial CD8+, CD4+ and GZB+ cells than p16Ink4a-positive tumors (p=0.032, p=0.016 and p=0.007 respectively). High-risk HPV-status did not correlate with the infiltration of immune cells. Median follow up was 89.20 months (range 1.7-189.5). High CD4+ and CD56+ indices were correlated with prognosis in p16Ink4a–positive cases (p=0.039 and p=0.013 respectively). Low CD68+ infiltrates were correlated with prognosis in p16Ink4a-negative cases (p=0.018). Conclusion: p16Ink4a-status impacts local immune surveillance as represented by tumor infiltrating immune cells. Immunologic effects contributing to clinical outcome might depend on p16Ink4a-overexpression.

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