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Introduction/Background* Molecular landscape and carcinogenesis of vulvar squamous cell carcinoma (VSCC) have been poorly explored and lack a biomarker-driven targeted therapy. In this non-systematic review we aimed to summarize findings of studies exploring molecular landscape of VSCC. Methodology Key word search was conducted (PubMed, Scopus) in January 2021, using the terms (“vulvar” and “cancer” or “carcinoma”) and (“molecular” or “genomic” or “mutation”). Observational studies evaluating molecular alterations in VSCC were deemed eligible. Pre-specified data were extracted from the selected articles, including the number of samples analyzed, DNA sequencing technique, number and frequency of identified mutations, HPV prevalence and prognostic data. Result(s)* Fourteen studies published between 2005 and 2020 were identified, including a total of 747 VSCC samples. Selected studies were highly heterogeneous in terms of DNA sequencing and HPV testing strategies and included small samples. Twelve studies performed next generation sequencing (NGS), nine of whom used targeted approach, two used whole exome sequencing and one used whole genome sequencing. The two remaining studies used multiplex ligation-dependent probe amplification assay and Sanger sequencing. The most frequently studies and mutated genes were TP53 and CDKN2A, followed by PIK3CA, HRAS and PTEN (table 1). Evidence on genomic differences between HPV-associated and -independent VSCC is particularly scarce and variable between studies. Only a single, targeted NGS study showed notorious differences in molecular profiles based on HPV status. Accumulated evidence indicates that in HPV-associated VSCC more frequently involves PI3K/AKT/mTOR pathway, involving HRAS, KRAS, PIK3CA, KMT2D, PTEN and FBXW7 mutations. On the other hand, HPV-independent VSCC involve alterations in TP53, CDKN2A, CCND1. The prognostic role of molecular alterations in VSCC was assessed in seven articles, with discordant results. Some articles suggest that TP53 alterations are associated to worse prognosis in patients with VSCC, particularly when combined with PIK3CA, HRAS or CDKN2A. Conclusion* Limitations and heterogeneity of available molecular series contribute to a limited view of the molecular landscape of VSCC. Prognostic or therapeutic roles of identified mutations and pathways in VSCC remain to be elucidated. Large-scale, genome or exome-wide studies with robust HPV testing are necessary to expand the knowledge on molecular landscape in VSCC.

Introduction/Background* The aim of this study was to correlate the serum concentrations of tumor markers HE4 and CA125 with the tumor burden evaluated through the volumetric parameters of FDG-PET/CT FDG in patients with advanced epithelial ovarian cancer (EOC) before primary treatment. Methodology Sixty-six patients with advanced stage high grade serous ovarian carcinoma (HGSOC) or undifferentiated carcinoma (UOC) were included. Serum HE4, serum CA125 and FDG PET/CT were performed before primary treatment. Volumes of interest (VOIs) were delimited on every pathological uptake in PET images. Whole-body metabolic tumor volume (wbMTV) and total lesion glycolysis (wbTLG) were calculated as the sum of every single VOI value. SUVmax thresholds were set at 40% and 50%. Four VOIs subgroups were defined for analysis: carcinomatosis, retroperitoneal, supradiaphragmatic and metastases. MTV and TLG values were calculated for each of them. The associations between these parameters and serum tumor markers were assessed through Pearson and Spearman tests. Result(s)* When correlating wbMTV and wbTLG with both CA125 and HE4, significant associations were found. The strongest correlation was observed between HE4 and wbMTV40% (r=0.61, p Conclusion* Peritoneal tumor burden measured by FDG PET/CT volumetric parameters correlates better with HE4 than with CA125 in patients with advanced epithelial ovarian cancer. These results support the increasing utility of HE4 to improve the stratification of these patients in clinical practice

Introduction/Background* Systematic pelvic and paraortic lymphadenectomy is part of the initial epithelial ovarian cancer (EOC) staging surgery but this procedure is associated with potential severe morbidity. Moreover, there is no evidence suggesting a possible therapeutic value. The detection of the sentinel lymph node (SLN) in the early stage of EOC is in the experimental phase and there is little literature about it. This study evaluates the lymphatic mapping with radiotracer and indocyanine green (ICG)) and the detection of ovarian SLN. Methodology Prospective cohort study in ovarian masses suspected of malignancy or re-staging surgery after confirmed malignancy. Albumin [99mTc] Tc-nanocolloid was injected into the utero-ovarian and infundibulo-pelvic ligaments. After 15 minutes, intraoperative images were acquired with a portable gammacamera. Subsequently, the adnexectomy and intraoperative pathological analysis were performed. In the cases in which malignancy was confirmed, ICG was injected proximally to the sectioned area of the ligaments and the lymphatic chains were traced with the fluorescence camera prior to the pelvic and paraortic lymphadenectomy. Ultrastaging of the SLN was done. The follow-up for possible adverse events lasted 30 days after surgery. Result(s)* 20 patients were included between September-2020 and May-2021. Ovarian carcinoma was confirmed in 8 (40%) cases. In all cases gamma probe was used, in 60% the gamma camera and 40% the fluorescence camera. Some SLN was detected in 18/20 cases (90%) with exclusive paraortic drainage in 5/18 (28%), pelvic in 1/18 (6%) and in both territories in 12/18 (66%). Overall para-aortic drainage was observed in 17/18 (94%) patients (35% supramesenteric, 30% at the level of the inferior mesenteric artery, and 35% inframesenteric). 100% of aortic SLNs were detected with a gamma probe after being visualized with the gamma camera. In the 8 patients who underwent lymphadenectomy, 1 case had positive nodes diagnosed by ultrastaging and the rest of the lymph nodes were negative. No complications related to the technique were observed. Conclusion* The SLN technique is feasible and safe. The intraoperative gamma camera shows the lymphatic map and is especially useful in the paraortic region.

Introduction/Background* In patients with early-stage, grade 1-2, endometrioid endometrial cancer, preoperative assessment of myometrial invasion is essential to define the need of pelvic and paraaortic lymph node dissection. Our aim was to evaluate the role of three-dimensional transvaginal ultrasound (3D-TVUS) and diffusion-weighted magnetic resonance imaging (DW-RMI) for the assessment of myometrial infiltration in patients with well-differentiated (G1) or moderately differentiated (G2) endometrioid endometrial carcinoma (EC). Methodology We performed a retrospective observational study. Myometrial infiltration was assessed by 3D-TVUS and DW-MRI in 152 women with G1 or G2 endometroid EC who underwent surgical treatment in a tertiary referral center between 2012 and 2019. Sensitivity, specificity, predictive values and accuracy for the two techniques and for a combination of both were computed. Definitive histopathological data in the surgical specimen regarding myometrial infiltration was used as ‘Gold Standard’. Result(s)* One hundred and fifty-two patients were included, 120 (79%) patients presented myometrial infiltration 50%). 3D-TVUS and DW-MRI showed an agreement of 78.9% with a kappa index of 0.44 for the detection of deep myometrial infiltration. Sensitivity, specificity and accuracy of 3D-TVUS for the detection of deep myometrial infiltration were 71.0%, 80.5% and 78.5% respectively. Evaluation of myometrial infiltration with DW-MRI had a sensitivity, specificity and accuracy of 76.2%, 84.4% and 82.9% respectively. Association of both techniques increased sensitivity and specificity up to 84.6% and 93.2% and provided a low false negative rate (2.3%). Conclusion* The combination of 3D-TVUS and DW-RMI offers a high sensitivity and specificity to identify deep myometrial infiltration in patients with endometrioid G1 or G2 EC, thus these patients might benefit from performance of both techniques in preoperative evaluation.

Introduction/Background In early-stage cervical cancer, nodal involvement remains the most important prognostic factor. Imaging evaluation is not sensitive enough to replace histology. Achieving high detection rates is a prerequisite to introduce sentinel lymph node biopsy (SLNB). The aim of this study was to evaluate the evolution of SLNB detection techniques in women with early-stage cervical cancer treated in our institution. Methodology From 02/2001 until 01/2019, patients with FIGO 2009 stages IA1-IB1/IIA1 cervical carcinoma underwent SLNB. Those treated until 01/2010 endured SLNB followed by pelvic bilateral lymphadenectomy, thereafter only SLNB was performed. When SLNs were detected unilaterally or not detected, lymphadenectomy of the failed mapped side was performed. SLNB was achieved by laparoscopy after intracervical injection: first with blue dye (BD) plus radiocolloid (Tc) and, since 2014, with indocyanine green (ICG) also. SLN identification was performed with lymphoscintigraphy and SPECT/CT, facilitated by a laparoscopic gamma-probe and a fluorescence camera. Detection rate was calculated as the number of procedures in which at least one SLN was identified intraoperatively, divided by the total number of procedures undertaken. Results From 164 patients treated, 129 underwent SLNB with BD+Tc and 35 with BD+Tc+ICG. No differences regarding age at diagnosis, size of the tumor (≤2 cm vs >2 cm), FIGO stage, histologic subtype and surgical radicality were seen between both groups. In the first group, at least one SLN was identified in 123 cases, for an overall detection rate of 95.4%. The rate of bilateral detection was 61.2%. For the triple-technique group we detected SLNs in 35 cases, prompting a detection rate of 100%. SLNs were bilaterally detected in 34 patients (97.1%). Conclusion Both implemented techniques for SLNB in early-stage cervical cancer show a high detection rate. Nevertheless, triple technique with BD+Tc+ICG allows bilateral SLN detection in almost all patients. Disclosure Nothing to disclose.

Introduction/Background It has been suggested that the evaluation of the expression of host-cell genes involved in cervical carcinogenesis induced by high-risk human papillomavirus (HR-HPV) may be useful to identify patients harbouring high-grade squamous intraepithelial lesions (HSIL). We aimed to evaluate the performance of mRNA detection of three biomarkers (CDKN2A, MKi67, TOP2A) in liquid-based cytology (LBC) to identify HSIL. Methodology Observational prospective study including 250 patients referred to colposcopy. Patients underwent Pap-test, HR-HPV testing, colposcopy, and at least one biopsy. CDKN2A, MKi67 and TOP2A mRNA was detected in LBC specimens by reverse transcription and quantitative polymerase chain reaction. Among HR-HPV positive patients, 49 showed negative pathological findings, 38 harboured low-grade squamous intraepithelial lesions (LSIL), 105 harboured HSIL, and 17 showed discordant results between cytology (HSIL) and biopsy (LSIL). Thirty-five patients were HR-HPV negative and presented negative biopsies (control group). mRNA expression was quantified using ΔCycle threshold and compared between groups. We performed ROC analysis and computed sensitivity and specificity of mRNA expression for HSIL detection. Results Two hundred and forty-three (97.2%) LBC samples yielded adequate material for mRNA determination. We found higher expression of the three biomarkers in HSIL group compared to control group (p Table 1 shows area under the curve (AUC), sensitivity and specificity of the biomarkers for HSIL detection, at the optimal cut-off point according to ROC curve. Conclusion Detection of mRNA of CKN2A, MKi67 and TOP2A in LBC samples showed higher sensitivity than Pap-test to identify women with HSIL. Further studies are needed to confirm that host-cell mRNA detection might have a role in secondary prevention of cervical cancer. Disclosure Nothing to disclose.

Introduction/Background In early FIGO stage patients (IA, IB1 and IIA1) nodal involvement is one of the most important prognostic factors. Pelvic lymphadenectomy (LDN) is performed in order to assess lymph node involvement. Sentinel lymph node (SLN) biopsy has been increasingly used with limited evidence of oncological safety. Methodology Patients with FIGO stage IA1-IB1/IIA1 cervical carcinoma treated with radical surgery after lymph node assessment in Hospital Clinic (Barcelona, Spain) from 2001 to 2018 were included. Between 02/2001 and 05/2011 patients underwent SLN biopsy followed by complete pelvic LDN and patients from 06/2011 and 08/2018 underwent SLN dissection alone. Patients in whom SLN were detected unilaterally or not detected underwent a complete LDN of the failed mapped side. Radical surgery after intraoperative negative nodes were laparoscopic assisted vaginal radical hysterectomy or vaginal radical trachelectomy if fertility preservation desire. SLN were postoperative evaluated by pathologic ultrastaging. Intraoperative and postoperative as well as follow up data were prospectively recorded. STATA 15.1 was used for statistical analysis. Results In 162 patients lymph node assessment was performed, 87 (53.7%) underwent SLN biopsy followed by pelvic bilateral LDN and 75 (46.3%) SLNB only. No differences regarding age at diagnosis, size of the tumor (≤2 cm vs >2 cm), FIGO stage or histology type were seen between both groups. 151 patients had negative nodes. From these patients, 7 patients (9.1%) recurred in the LDN group and 3 patients (4.3%) in the SLN group. Cox hazard ratios were not statistically significant for lymph node assessment group. Conclusion Sentinel lymph node detection in patients with early cervical cancer does not entail an increased risk of recurrence with respect to the patients in whom a complete pelvic lymphadenectomy is performed. Disclosure The authors have no relationships/conditions/circumstances that present a potential conflict of interest.

Introduction/Background The aim was to evaluate the impact on survival depending on paraaortic (PA) nodes involvement and size of metastasis in locally advanced cervical cancer (LACC) after staging surgery and its safety before applying chemoradiotherapy treatment. Methodology We conducted a retrospective study in patients with LACC (FIGO stages from IB2 to IVA) from 2000 to 2016. All patients underwent MRI imaging and a laparoscopic staging PA lymphadenectomy (LSPAL). We performed an accurate ultrastaging of positive PA nodes and classified them in two groups (node metastasis >5 mm vs ≤5 mm) in order to compare the overall survival (OS). Radiation fields were extended to the PA area only in patients with PA nodes involvement. We evaluated the morbidity and mortality of the surgery. Results One hundred eighty three patients were diagnosed as a LACC. One hundred fifty patients had squamous carcinoma and thirty three patients adenocarcinoma. We observed 34 (18.5%) patients with PA nodal involvement (8 patients with PA metastasis measuring ≤5 mm and 20 measuring >5 mm). Six patients with lymph node metastasis did not have an ultrastaging study and were excluded from the analysis. Hazar Ratio for OS at 15 years were 2.51 (CI 0.90–6.98) for ≤5 mm metastasis (p 0.08) and 2.34 (CI 1.27–4.32) for >5 mm metastasis (p 0.007). Regarding surgical complications, 4 intraoperative events were reported (2,19%) although no perioperative mortality occurred. Thirteen (7.14%) early complications during the first month and 7(3.91%) late complications were reported with no mortality events. Conclusion The size of the paraaortic lymph node metastasis in patients with LACC has prognostic implications. Overall survival in patients with negative nodes or with metastasis ≤5 mm is similar. Paraaortic lymph node staging and extended-field radiotherapy represent a survival benefit in cases with positive nodes ≤5 mm. In LACC patients LSPAL seems a safe procedure. Disclosure Nothing to disclose.

Introduction/Background The aim of this study was to analyze the oncological outcomes and risk factors for recurrence of vaginal fertility-sparing surgery (FSS) and laparoscopic sentinel lymph node biopsy (SLNB) in patients with early cervical cancer (CC). Methodology From March 2005 to April 2018, 38 patients diagnosed with early stage CC underwent vaginal FFS at the Hospital Clinic, Barcelona, Spain. Patients with FIGO stage IA1 with lymphovascular space invasion (LVSI) and stage IA2 underwent simple trachelectomy and patients with stage IB1 underwent vaginal radical trachelectomy (VRT). All cases underwent laparoscopic SLNB. In the first cases, laparoscopic bilateral pelvic lymphadenectomy (LBPL) was completed immediately after SLNB. Clinical and oncological follow-up data were prospective collected. Results The median age at diagnosis was 33.5 years old (range 22–44). Simple trachelectomy was performed in seven cases (18.4%) and VRT in 31 (81.6%). Nineteen patients were treated with laparoscopic SLNB exclusively and 19 with SLNB plus LBPL. There were no significant differences between the two groups regarding histology and tumor size. The median follow-up was 73 months (range 1–160 months). There were 4 recurrences (3 patients with IB1 and one in IA2). Two occurred in the SLNB group and 2 in the SLNB plus LBPL group. All recurrences were diagnosed in patients with adenocarcinoma tumors and three without LVSI. Conclusion Vaginal FFS with laparoscopic SLNB seems to be a safe oncological procedure in early stage CC patients. Further studies are needed to clarify the role of adenocarcinoma histology as a prognostic factor of recurrence. Disclosure Nothing to disclose.