PD-L1 expression and survival in p16-negative and -positive squamous\xa0cell carcinomas of the vulva

Bastian Czogalla,Miriam Rottmann,Elisa Schmoeckel,Doris Mayr,Sven Mahner,Deborah Pham,Alexander Burges,Udo Jeschke,Fabian Trillsch,Thomas Kirchner,Julia Gallwas

doi:10.1007/s00432-020-03126-9

Abstract

AimProgrammed death-ligand 1 (PD-L1) has become a widely used predictive biomarker for therapy with checkpoint inhibitors in a variety of cancers. Here, we studied the expression of PD-L1 in squamous cell carcinomas of the vulva (SCCV) with regard to HPV status via its surrogate marker p16. Additionally, the status of PD-L1 and p16 were analyzed for prognostic information and potential correlation to tumor-infiltrating lymphocytes (TILs).MethodsPD-L1 was analyzed in 128 cases of SCCV using the tumor proportion score (TPS), the immune cell score (ICS) and the combined positive score (CPS). Cases were immunostained for p16 and analyzed for stromal TILs. PD-L1, p16, and TILs were compared to clinico-pathological parameters and patient’s survival.ResultsTPS ≥ 50% and CPS ≥ 50 were correlated to a worse grading (p = 0.028 and p = 0.031), but not to FIGO-stage. CPS ≥ 50 was associated to a worse prognosis with overall survival (p = 0.021) but was not correlated to the progression-free survival. P16-positivity was correlated to a longer progression-free survival (p = 0.006) and overall survival (p = 0.023). PD-L1 expression was independent from p16 status. TILs ≥ 50% were present in 24% of the cases and were strongly correlated to PD-L1 (TPS p = 0.02, ICS p < 0.001, CPS p = 0.001).ConclusionOur data demonstrate that PD-L1 expression is frequent in SCCV and independent from p16 status. High PD-L1 expression was associated with an unfavorable outcome whereas p16-positivity turned out to be an independent positive prognostic factor.

Highlights

Squamous cell carcinoma of the vulva (SCCV) is a relatively rare disease, accounting for 5% of all gynecologic malignancies (Siegel et al 2016)
Programmed death-ligand 1 (PD-L1) positivity was observed in the majority of the cases: tumor proportion score (TPS) ≥ 1% was found in 83%, immune cell score (ICS) ≥ 1% in 93%, and combined positive score (CPS) ≥ 10 in 66%
TPS ≥ 50% was significantly correlated to ICS ≥ 10% (p = 0.026) and CPS ≥ 50 (p < 0.001)

Summary

Introduction

Squamous cell carcinoma of the vulva (SCCV) is a relatively rare disease, accounting for 5% of all gynecologic malignancies (Siegel et al 2016). Incidence rates are increasing, due to increase in younger women (Lai et al 2014; Schuurman et al 2013; Hampl et al 2008). SCCV can be either human papillomavirus (HPV)-associated or -independent. Up to 25–40% are linked to HPV-infection and the other group to chronic inflammatory and degenerative skin diseases, lichen sclerosus (Gargano et al 2012; Del Pino et al 2013). Compared to oropharyngeal squamous cell carcinoma, the prognostic impact of HPV is considerably less established in SCCV. Indications increase that HPV-linked SCCV have a more favourable prognosis (Sand et al 2019; Lee et al 2016).

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