PD-L1 expression on immune cells is a favorable prognostic factor for vulvar squamous cell carcinoma patients PD-L1 expression on immune cells is a favorable prognostic factor for vulvar squamous cell carcinoma patients

Objective Adaptive immune effectors do not influence prognosis in vulvar squamous cell carcinoma (vSCC). Therefore, we tried to clarify the prognostic role of innate immunity and granzyme B-dependent cytotoxicity as defined by intratumoral infiltrates of natural killer cells (CD56+) and lymphocytes expressing granzyme B (GrB+). Methods We analyzed 76 primary vSCCs and 35 lymph node metastases that were obtained from 76 patients with a full clinical history. The distribution and density of GrB+ and CD56+ cells within cancer tissues were evaluated by immunohistochemistry and correlated with clinicopathological features, commonly recognized prognostic factors and overall survival (OS). Results CD56+ cells were mostly detected within the cancer nests, while GrB+ cells were predominant in the tumor stroma. Intraepithelial (IE) CD56+ infiltrates at the primary site were correlated with depth of invasion (r = 0.339, p = 0.003) and recurrence (r = 0.295, p = 0.011), while IE GrB+ infiltrates were correlated with tumor grade (r = 0.304, p = 0.009) and age (r = 0.333, p = 0.004). The primary cancer nests of metastatic patients were infiltrated more by intraepithelial (IE) CD56+ cells than were those of the non-metastatic patients (p = 0.05). The median OS was 41.16 months (range 1.7–98.43). High IE GrB+ infiltrates predicted longer OS among patients without metastases (p = 0.028). High IE CD56+ infiltrates were correlated with longer OS in metastatic cases (p = 0.009). Conclusion The combined cytotoxicity of innate and adaptive immune effectors infiltrating cancer nests (IE GrB+) predicts an improved clinical outcome among non-metastatic vSCC patients. The functional status of prognostic IE CD56+ infiltrates in immune escaped (metastatic) tumors requires further investigation.

We aimed to evaluate the correlation between p16ink4a-overexpression and high risk (hr)HPV-DNA in vulvar squamous cell carcinoma (vSCC) tumors as well as the impact of both biomarkers on the prognosis of vSCC patients. PCR-detection of (hr)HPV-DNA and immunohistochemical staining for p16ink4a were conducted in 85 vSCC tumors. Survival analyses included the Kaplan–Meier method, log-rank test and Cox proportional hazards model. p16ink4a-overexpression and (hr)HPV-DNA were detected in 35 and 37 of the 85 tumors, respectively. Among the 35 p16ink4a-positive tumors, 10 lacked (hr)HPV-DNA (29 %). Among the 50 p16ink4a-negative tumors, (hr)HPV-DNA was detected in 12 cases (24 %). The median follow-up was 89.20 months (range 1.7–189.5 months). P16ink4a-overexpression, but not (hr)HPV-DNA positivity of the primary tumor, was correlated with prolonged overall survival (OS) (p = 0.009). P16ink4a-overexpression predicted a better response to radiotherapy (p < 0.001). Univariate analysis has demonstrated that age (p = 0.025), tumor grade (p = 0.001), lymph node metastasis (p < 0.001), FIGO stage (p < 0.001), p16ink4a-overexpression (p = 0.022), and adjuvant RTX (p < 0.001) were prognostic factors for OS. Multivariate analysis has demonstrated that lymph node metastasis (HR 1–2.74, 95 % CI 1.50–5.02, p = 0.019), tumor grade (HR 1–2.80, 95 % CI 1.33–5.90, p = 0.007) and p16ink4a-overexpression (HR 1–2.11, 95 % CI 1.13–3.95, p = 0.001) are independent prognostic factors. The discovered overlap suggests the use of p16ink4a in combination with HPV-DNA detection as an ancillary test for future research and clinical studies in vSCC. The prognostic and predictive value of p16ink4a-overexpression should be tested in larger cohort studies.

In 2009, International Federation of Gynecology and Obstetrics (FIGO) modified staging of vulvar cancer—the prognostic significance of the new classification relative to the prior system as well as to the commonly recognized prognostic factors has not been assessed. The aim of this study was to test prognostic ability of 2009 staging in a cohort of uniformly treated and staged cases with long-term follow-up. Pathologic characteristics were obtained by blind review of the original tissue samples. 76 patients who qualified for surgery on the basis of the same criteria, with full clinical history, were included in the study. The histological analyses were performed on 76 and 35 paraffin-embedded tissue samples from primary tumors and lymph nodes, respectively. Survival analyses included the Kaplan–Meier method, log-rank test and Cox proportional hazards model. Univariate analysis has demonstrated that age (p = 0.0170), lymph node metastasis (p = 0.0393), tumor grade (p = 0.0086) and FIGO1994 stage (p = 0.001) were the significant prognostic factors for overall survival. Multivariate analysis has demonstrated that growing age (HR 2.25, 95 % CI 0.79–3.71, p = 0.0321), tumor grade (G1 vs. G2 and G3) (HR 1–3.11, 95 % CI 1.6–4.62, p = 0.0057) and FIGO1994 stage (HR 1.78, 95 % CI 0.55–3.01, p = 0.0061) are independent prognostic factors with respect to overall survival. The results indicate the prognostic advantage of the 1994 FIGO staging as it has become an independent prognostic factor in contrast to the new FIGO system. This should be tested in future larger cohort studies. Differentiation grade turned out to be a very valuable independent prognostic factor and should be incorporated as a routine component of the histopathologic reports in vulvar cancer.

Background: Due to the increasing amount of published data suggesting that endometrial carcinoma is a heterogenic entity with possible different treatment sequences and post-treatment follow-up, the Polish Society of Gynecological Oncology (PSGO) has developed new guidelines. Aim: to summarize the current evidence for diagnosis, treatment, and follow-up of endometrial carcinoma and to provide evidence-based recommendations for clinical practice. Methods: The guidelines have been developed according to standards set by the guideline evaluation tool AGREE II (Appraisal of Guidelines for Research and Evaluation). The strength of scientific evidence has been defined in agreement with The Agency for Health Technology Assessment and Tariff System (AOTMiT) guidelines for scientific evidence classification. The grades of recommendation have been based on the strength of evidence and the level of consensus of the PSGO development group. Conclusion: Based on current evidence, both the implementation of the molecular classification of endometrial cancer patients at the beginning of the treatment sequence and the extension of the final postoperative pathological report of additional biomarkers are needed to optimize and improve treatment results as well as to pave the route for future clinical trials on targeted therapies.

Background: Maintenance therapy with PARP inhibitors and bevacizumab is approved for ovarian cancer treatment in the first and second line settings, but selecting the optimal sequence is challenging due to restrictions on using the same medication twice. This review aims to establish guidelines for ovarian cancer maintenance therapy based on the strength of scientific evidence, the most effective treatment strategy, and the impact on the healthcare system. Methods: Six questions were formulated to evaluate the scientific evidence supporting different maintenance therapy options using the AGREE II guideline evaluation tool. The questions address the acceptability of reusing the same medication, the efficacy of bevacizumab and PARP inhibitors in the first and second line settings, the comparative efficacy of these medications, the potential benefit of combination maintenance therapy, and the economic impact of maintenance therapy. Results: Based on the available evidence, bevacizumab should be preserved for second line maintenance therapy, and maintenance therapy with PARP inhibitors should be offered to all advanced ovarian cancer patients who have responded to first line platinum-based chemotherapy. Additional molecular predictors for bevacizumab efficacy are needed. Conclusions: The presented guidelines offer an evidence-based framework for selecting the most effective maintenance therapy for ovarian cancer patients. Further research is necessary to refine these recommendations and improve outcomes for patients with this disease.