The Role of P16, P53, KI-67 and PD-L1 Immunostaining in Primary Vaginal Cancer

SIMPLE SUMMARY: To date, vaginal cancer is the only tumor entity of the female genital tract without a practical guideline within the National Comprehensive Cancer Network (NCCN). Therapeutic options vary between surgery for Stage I disease and concurrent chemoradiation for Stage II to IV disease. The lack of data regarding systemic therapies remains challenging to overcome as vaginal cancer is too rare to conduct large, randomized trials. By assessing pathological and immunhistochemical variables in this rare tumor entity, as well as the clinical courses of patients treated within different treatment schedules including immunotherapy and anti-VEGF-therapy, we aimed to show similarities to cervical cancer where emerging therapeutic options have improved survival significantly. ABSTRACT: Background: To analyze clinical, pathological and immunohistochemical correlates of survival in vaginal cancer patients. Methods: Retrospective analysis of primary vaginal cancer patients, treated at the Department of Gynecology and Gynecological Oncology of the University Hospital Bonn between 2007 and 2021. Results: The study cohort comprised 22 patients. The median age was 63 years (range: 32–87 years). Squamous cell histology was present in 20 patients. Five-year OS in Stage I, II, III and IV was 100%, 56.25%, 0% and 41.67%, respectively (p = 0.147). Five-year DFS was 100%, 50%, 0% and 20.83%, respectively (p = 0.223). The 5-year OS was significantly reduced in the presence of nodal metastasis (p = 0.004), lymphangiosis (p = 0.009), hemangiosis (p = 0.002) and an age above 64 years (p = 0.029). Positive p 16 staining was associated with significantly improved OS (p = 0.010). Tumoral and immune cell PD-L1 staining was positive in 19 and in 16 patients, respectively, without significant impact on OS; 2 patients with metastastic disease are long-term survivors treated with either bevacizumab or pembrolizumab. Conclusion: P16 expression, absence of lymph- or hemangiosis, nodal negative disease and an age below 64 years show improved survival rates in PVC. Tumoral PD-L1 expression as well as PD-L1 expression on immune cells is frequent in PVC, without impacting survival. Within our study cohort, long-term survivors with recurrent PVC are treated with anti-VEGF and immunotherapy.