Histopathological biomarkers in squamous cell carcinoma of the vulva: the prognostic relevance of tumor-infiltrating lymphocytes (TILs) : a retrospective study of 157 cases

Abstract

Background The prognostic relevance of tumor-infiltrating lymphocytes (TILs) has so far been recognized in several solid tumors like in breast, endometrial and ovarian cancer—nonetheless, the immune contexture of squamous cell carcinomas of the vulva, analyzed by means of stromal (s) and intratumoral (i) TILs, remains yet to be elucidated. Material and methods In this study, we examined the immunooncological biomarkers sTILs and iTILs in 157 vulvectomy specimens with histologically diagnosed vulvar squamous cell carcinoma (VSCC) according to the standardized methodology proposed by the International Immunooncology Biomarkers Working Group in 2017. In a next step, we evaluated the association of infiltrating lymphocytes to traditional histopathological parameters such as infiltration depth and HPV related tumorigenesis. After determining optimal cut-off values using Receiver Operating Characteristic (ROC) curve analysis, we assessed the prognostic relevance of sTILs and iTILs with regard to overall survival, local recurrence, and metastasis using the Log-rank (Mantel–Cox) test and Fisher's exact test. Results We propose optimal cut-off values of 5% for iTILs and 20% for sTILs analysis, which identify patients with a distinct superior survival rate (sTILs: p = 0.0137; iTILs: p = 0.0226). Furthermore, a low number of iTILs was associated with a higher risk of local recurrence in our study collective (p = 0.0432). Conclusion The fast and cost-effective determination of the histological biomarkers iTILs and sTILs yields prognostic relevance in vulvar cancer. A potential integration within the routine diagnostic workflow could be globally feasible, even in resource-poor settings.