Papillomavirus genotyping on formaldehyde fixed paraffin-embedded tissues in vulvar intraepithelial neoplasia.

PURPOSE: Few studies have described the epidemiology of human papillomavirus (HPV) in vulvar intraepithelial neoplasia (VIN). The aim of this study was to genotype HPV on formalin fixed paraffin-embedded tissues in VIN lesions. METHODS: A 5-year retrospective study was conducted by including all patients attending the teaching hospital of Nice with a diagnosis of VIN between 1st January 2010 and 31st December 2014. For all patients, HPV genotyping was performed with the PapilloCheck® microarray kit, routinely used on cervical cytology samples, and optimized for formaldehyde fixed paraffin-embedded tissues in VIN. RESULTS: Forty patients were included in the study: 39 patients had usual VIN and one presented with differentiated VIN. Among the 39 patients with usual VIN, the prevalence of HPV was 90% (35/39). Thirty-two patients had high grade VIN (82%) and seven low grade VIN (18%). In high grade VIN, the most represented HPV types were: HPV 16 (21/32 66%), HPV 56 (3/32 9%) and HPV 33 (2/32 6%). In low grade VIN, the most represented HPV types were: HPV 16 (4/7 57%) and HPV 6 (3/7 43%). Interestingly, 5/39 (13%) of patients diagnosed with usual VIN also had co-existing lichen sclerosus. CONCLUSIONS: We have optimized a HPV genotyping technique, routinely used on cervical cytology samples, and on paraffin fixed embedded tissue showing VIN. Moreover, we have identified five patients with lichen sclerosus co-existing with usual VIN. This association has rarely been reported and proves that these two entities can coexist.

Pembrolizumab in soft-tissue sarcomas with tertiary lymphoid structures: a phase 2 PEMBROSARC trial cohort.

Immune checkpoint inhibitors (ICIs) show limited clinical activity in patients with advanced soft-tissue sarcomas (STSs). Retrospective analysis suggests that intratumoral tertiary lymphoid structures (TLSs) are associated with improved outcome in these patients. PEMBROSARC is a multicohort phase 2 study of pembrolizumab combined with low-dose cyclophosphamide in patients with advanced STS (NCT02406781). The primary endpoint was the 6-month non-progression rate (NPR). Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety. The 6-month NPR and ORRs for cohorts in this trial enrolling all comers were previously reported; here, we report the results of a cohort enrolling patients selected based on the presence of TLSs (n = 30). The 6-month NPR was 40% (95% confidence interval (CI), 22.7-59.4), so the primary endpoint was met. The ORR was 30% (95% CI, 14.7-49.4). In comparison, the 6-month NPR and ORR were 4.9% (95% CI, 0.6-16.5) and 2.4% (95% CI, 0.1-12.9), respectively, in the all-comer cohorts. The most frequent toxicities were grade 1 or 2 fatigue, nausea, dysthyroidism, diarrhea and anemia. Exploratory analyses revealed that the abundance of intratumoral plasma cells (PCs) was significantly associated with improved outcome. These results suggest that TLS presence in advanced STS is a potential predictive biomarker to improve patients' selection for pembrolizumab treatment.