Search

Very little information is available on the mutational landscape of vulvar squamous cell carcinoma (VSCC), a disease that mainly affects older women. Studies focusing on the mutational patterns of the currently recognized etiopathogenic types of this tumor (human papillomavirus [HPV]-associated [HPV-A], HPV-independent [HPV-I] with TP53mutation [HPV-I/TP53mut], and HPV-I with wild-type TP53[HPV-I/TP53wt]) are particularly rare, and there is almost no information on the prognostic implications of these abnormalities.Whole-exome DNA sequencing of 60 VSCC and matched normal tissues from each patient was performed. HPV detection, immunohistochemistry (IHC) for p16, p53, and mismatch repair proteins were also performed. Ten tumors (16.7%) were classified as HPV-A, 37 (61.7%) as HPV-I/TP53mut, and 13 (21.6%) as HPV-I/TP53wt. TP53was the most frequently mutated gene (66.7%), followed by FAT1(28.3%), CDKN2A(25.0%), RNF213(23.3%), NFE2L2(20%) and PIK3CA(20%). All the 60 tumors (100%) were DNA mismatch repair proficient. Seventeen tumors (28.3%) showed CCND1gain. Bivariate analysis, adjusted for International Federation of Gynecology and Obstetrics stage, revealed that TP53mutation, CCND1gain, and the combination of the 2 alterations were strongly associated with impaired recurrence-free survival (hazard ratio, 4.4; P< .001) and disease-specific survival (hazard ratio, 6.1; P = .002). Similar results were obtained when p53 IHC status was used instead of TP53status and when considering only HPV-I VSCC. However, in the latter category, p53 IHC maintained its prognostic impact only in combination with CCND1gains. All tumors carried at least one potentially actionable genomic alteration. In conclusion, VSCCs with CCND1gain represent a prognostically adverse category among HPV-I/TP53mut tumors. All patients with VSCCs are potential candidates for targeted therapy.

Lymph node (LN) metastases are the most important prognostic factor in locally advanced cervical cancer. Paraaortic lymphadenectomy is the only method able to confirm the presence of metastasis and thereby help to determine the most adequate treatment approach. There is no standard regarding the minimal number of LNs that should be removed in paraaortic lymphadenectomy. Women with undiagnosed positive paraaortic LNs (false negatives) due to a low LN count do not receive extended-field radiation therapy, which may lead to worse survival outcomes. The aim of this study is to confirm LN metastases as poor prognosis and to assess whether in cases of locally advanced CC with negative paraaortic LN status, the number of paraaortic LN laparoscopically removed carries a prognostic value.

Human papillomaviruses (HPVs) are the causative agents of carcinoma of the uterine cervix. A number of HPV genotypes have been associated with cervical cancer and almost all tumors associated with HPV show strong p16 expression. However, there is little information on the possible impact of the HPV genotype and p16 immunostaining on the clinicopathological features or their prognostic value in cervical carcinoma. We evaluated a series of 194 patients with HPV-positive cervical cancers treated at our institution, focusing on the clinicopathological features and the relationship of the HPV genotypes and p16 immunostaining with the prognosis. A single HPV type was identified in 149 (77%) tumors, multiple HPV infection was detected in 30 cases (15%), and undetermined HPV type/s were identified in 15 (8%) carcinomas. HPV 16 and/or 18 were detected in 156 (80%) tumors. p16 was positive in 186 (96%) carcinomas, but eight tumors (4%) were negative for p16 (seven squamous cell carcinomas, one adenocarcinoma); 5/8 caused by HPV 16 and/or 18. Patients with HPV 16 and/or 18 were younger (49 ± 15 vs. 57 ± 17 years, p< 0.01) and more frequently had nonsquamous tumors than patients with other HPV types (24% [37/156] vs. 0% [0/38]; p= 0.01). Neither the HPV type nor multiple infection showed any prognostic impact. Patients with p16-negative tumors showed a significantly worse overall survival than women with p16-positive carcinomas (45 vs. 156 months, p= 0.03), although no significant differences in disease-free survival were observed. In the multivariate analysis, negative p16 immunostaining was associated with a worse overall survival together with advanced FIGO stage and lymph node metastases. In conclusion, the HPV genotype has limited clinical utility and does not seem to have prognostic value in cervical cancer. In contrast, a negative p16 result in patients with HPV-positive tumors is a prognostic marker associated with a poor overall survival.

Human papillomaviruses (HPVs) are the causative agents of carcinoma of the uterine cervix. A number of HPV genotypes have been associated with cervical cancer and almost all tumors associated with HPV show strong p16 expression. However, there is little information on the possible impact of the HPV genotype and p16 immunostaining on the clinicopathological features or their prognostic value in cervical carcinoma. We evaluated a series of 194 patients with HPV-positive cervical cancers treated at our institution, focusing on the clinicopathological features and the relationship of the HPV genotypes and p16 immunostaining with the prognosis. A single HPV type was identified in 149 (77%) tumors, multiple HPV infection was detected in 30 cases (15%), and undetermined HPV type/s were identified in 15 (8%) carcinomas. HPV 16 and/or 18 were detected in 156 (80%) tumors. p16 was positive in 186 (96%) carcinomas, but eight tumors (4%) were negative for p16 (seven squamous cell carcinomas, one adenocarcinoma); 5/8 caused by HPV 16 and/or 18. Patients with HPV 16 and/or 18 were younger (49 ± 15 vs. 57 ± 17 years, p< 0.01) and more frequently had nonsquamous tumors than patients with other HPV types (24% [37/156] vs. 0% [0/38]; p= 0.01). Neither the HPV type nor multiple infection showed any prognostic impact. Patients with p16-negative tumors showed a significantly worse overall survival than women with p16-positive carcinomas (45 vs. 156 months, p= 0.03), although no significant differences in disease-free survival were observed. In the multivariate analysis, negative p16 immunostaining was associated with a worse overall survival together with advanced FIGO stage and lymph node metastases. In conclusion, the HPV genotype has limited clinical utility and does not seem to have prognostic value in cervical cancer. In contrast, a negative p16 result in patients with HPV-positive tumors is a prognostic marker associated with a poor overall survival.

Human papillomaviruses (HPV) are the causative agents of virtually all cervical carcinomas. Nevertheless, a small proportion of cervical cancer are negative for HPV, although the significance of this finding remains unclear. We aimed to provide insight into the differential clinico-pathological characteristics of this unusual subset of HPV-negative cervical cancer. We performed HPV-DNA detection using a highly sensitive PCR test (SPF10) and p16 immunostaining in 214 cervical carcinomas specimens from women treated at the Gynecological Oncology Unit of the Hospital Clinic (Barcelona, Spain) from 2012 to 2015. The clinical and pathological characteristics, including disease-free survival and overall survival, of HPV-negative and -positive cervical carcinomas were compared. Twenty-one out of 214 tumors (10%) were negative for HPV DNA. HPV-negative tumors were more frequently of the non-squamous type (9/21, 43% vs. 37/193, 19%; p< 0.01) and showed negative p16 staining (9/21; 43% vs. 7/193; 4%; p< 0.01). HPV-negative tumors were more frequently diagnosed at advanced FIGO stage (19/21, 91% vs. 110/193, 57%; p< 0.01) and more frequently had lymph node metastases (14/21, 67% vs. 69/193, 36%; p< 0.01). Patients with HPV-negative cervical cancer had a significantly worse disease-free survival (59.8 months, 95% confidence interval 32.0–87.6 vs. 132.2 months, 95% confidence interval 118.6–145.8; p< 0.01) and overall survival (77.0 months, 95% confidence interval 47.2–106.8 vs. 153.8 months, 95% confidence interval 142.0–165.6; p= 0.01) than women with HPV-positive tumors. However, only advanced FIGO stage and lymph node metastases remained associated with a poor disease-free survival and overall survival on multivariate analysis. In conclusion, our results suggest that a low percentage of cervical cancer arise via an HPV-independent pathway. These HPV-negative tumors are diagnosed at advanced stages, show higher prevalence of lymph nodes metastases and have an impaired prognosis.

Human papillomaviruses (HPV) are the causative agents of virtually all cervical carcinomas. Nevertheless, a small proportion of cervical cancer are negative for HPV, although the significance of this finding remains unclear. We aimed to provide insight into the differential clinico-pathological characteristics of this unusual subset of HPV-negative cervical cancer. We performed HPV-DNA detection using a highly sensitive PCR test (SPF10) and p16 immunostaining in 214 cervical carcinomas specimens from women treated at the Gynecological Oncology Unit of the Hospital Clinic (Barcelona, Spain) from 2012 to 2015. The clinical and pathological characteristics, including disease-free survival and overall survival, of HPV-negative and -positive cervical carcinomas were compared. Twenty-one out of 214 tumors (10%) were negative for HPV DNA. HPV-negative tumors were more frequently of the non-squamous type (9/21, 43% vs. 37/193, 19%; p< 0.01) and showed negative p16 staining (9/21; 43% vs. 7/193; 4%; p< 0.01). HPV-negative tumors were more frequently diagnosed at advanced FIGO stage (19/21, 91% vs. 110/193, 57%; p< 0.01) and more frequently had lymph node metastases (14/21, 67% vs. 69/193, 36%; p< 0.01). Patients with HPV-negative cervical cancer had a significantly worse disease-free survival (59.8 months, 95% confidence interval 32.0–87.6 vs. 132.2 months, 95% confidence interval 118.6–145.8; p< 0.01) and overall survival (77.0 months, 95% confidence interval 47.2–106.8 vs. 153.8 months, 95% confidence interval 142.0–165.6; p= 0.01) than women with HPV-positive tumors. However, only advanced FIGO stage and lymph node metastases remained associated with a poor disease-free survival and overall survival on multivariate analysis. In conclusion, our results suggest that a low percentage of cervical cancer arise via an HPV-independent pathway. These HPV-negative tumors are diagnosed at advanced stages, show higher prevalence of lymph nodes metastases and have an impaired prognosis.

Perivascular epitheliod cell tumor (PEComa) is a rare mesenchymal tumor. They are rare in the field of gynecology, which makes them difficult to consider as a possible diagnostic. We aim to contribute with our experience to ease clinical practice to others gynecologists.

To assess the effectiveness of the Mirena levonorgestrel-releasing intrauterine system (LNG-IUS) in peri- and postmenopausal women with endometrial hyperplasia without atypia.

Objective To analyze the utility of carbohydrate antigen (CA)125 and human epididymis protein 4 (HE4) to detect malignancy in women with ovarian endometriosis, when ovarian cancer is suspected and ultrasonography results are inconclusive.Methods Women who underwent surgery between 2015 and 2019 for ovarian endometriosis or for adnexal masses, with a final diagnosis of ovarian carcinoma (clear cell and endometrioid) were included in this retrospective study. The women were divided into three groups: ovarian endometriosis (OE), ovarian carcinoma without endometriosis (OC), and ovarian carcinoma with endometriosis (OC + E). Adnexal masses were assessed preoperatively by transvaginal ultrasonography according to the International Ovarian Tumor Analysis (IOTA) simple rules, and CA125 and HE4 blood levels were obtained.Results Of 208 women, 45 had malignancy, 16 in the OC + E group and 29 in the OC group. According to transvaginal ultrasonography, 13 were classified as undetermined risk of malignancy: OC group: 3, OE group: 3, and OC + E group: 7. When we compared the tumor biomarkers, significant differences in HE4 but not in CA125 levels were found between the groups.Conclusions When ovarian malignancy is suspected in patients with ovarian endometriosis, HE4 is a more useful tumor biomarker to diagnose OC when ultrasonography results are inconclusive.