Management of symptomatic uterine fibroids after ulipristal acetate suspension and identification of high risk patients for surgery at 6-months of follow-up.

OBJECTIVE: The use of ulipristal acetate (UPA) was indicated for the treatment of uterine fibroids. Following UPA suspension in March 2020, some patients presented worsening and required surgery. We aimed to identify patients at high-risk for undergoing surgery after UPA suspension. METHODS: We evaluated 85 women receiving intermittent UPA treatment until March 2020. Following UPA suspension, patients received other medical treatments or surgery. The clinico-pathological features were recoded and a quality of life health survey was completed by patients at the time of UPA suspension and at 6-months thereafter. RESULTS: After the suspension of UPA, 17 of the 85 patients receiving intermittent UPA (20%) required surgery, and 68 (80%) required other medical treatments. Patients who underwent surgery were younger and had greater fibroid volume. CONCLUSIONS: In our series, 20% of clinically stable patients receiving intermittent UPA required surgery following UPA suspension. These women should be considered for future medical strategies.

P16 and HPV Genotype Significance in HPV-Associated Cervical Cancer-A Large Cohort of Two Tertiary Referral Centers.

The expression of p16 is a good surrogate of human papillomavirus (HPV) infection in HPV-associated cancers. The significance of p16 expression, HPV genotype and genera in the outcome of patients with HPV-associated cervical cancer (CC) is unclear. Our aim is to ascertain the prognostic significance of these factors. Data from 348 patients (median age: 47.5 years old) with CC, diagnosed in two referral centers, were retrospectively collected. Advanced disease (FIGO2018 IB2-IV) was present in 68% of patients. A single HPV genotype was identified in 82.8% of patients. The most common HPVs were HPV16 (69%) and HPV18 (14%). HPV genera reflected this distribution. HPV16 tumors presented at an earlier stage. P16 was negative in 18 cases (5.2%), 83.3% of which were squamous cell carcinomas. These cases occurred in older patients who tended to have advanced disease. In the univariate analysis, HPV16 (HR: 0.58; p = 0.0198), α-9 genera (HR: 0.37; p = 0.0106) and p16 overexpression (HR: 0.54; p = 0.032) were associated with better survival. HPV16 (HR: 0.63; p = 0.0174) and α-9 genera (HR: 0.57; p = 0.0286) were associated with less relapse. In the multivariate analysis, only the International Federation of Gynecology and Obstetrics (FIGO) stage retained an independent prognostic value. HPV16, α-9 genera and p16 overexpression were associated with better survival, although not as independent prognostic factors. Patients with p16-negative HPV-associated CC were older, presented with advanced disease and had worse prognosis.

Prognostic implications of genotyping and p16 immunostaining in HPV-positive tumors of the uterine cervix.

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.

HPV-negative tumors of the uterine cervix.

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.

Impact of SARS-COV2 Pandemic on Patients with Endometriosis and Their Health Care.

Background: Endometriosis is a debilitating chronic inflammatory disease. The current SARS-COV2 pandemic has had an impact on the management of these patients. Tele-health care has been a relevant tool. The aim of this study was to analyze the impact of the SARS-COV2 pandemic on the perceived clinical health status and the type of care received in patients with endometriosis. Materials and Methods: We evaluated 945 premenopausal women treated at the Hospital Clinic of Barcelona between October 1 and December 31, 2020. Five hundred forty-nine women had endometriosis, and 396 had other benign gynecological diseases. An online health survey was sent to these patients. Clinicopathological features data were recorded. Results: Compared to patients with other benign gynecological diseases, a higher proportion of patients with endometriosis reported worsening of their symptoms (148/549, 27% vs. 85/396, 21.5%) and concern about their disease (515/549, 93.8% vs. 342/396, 86.4%), and more frequently received tele-health care (73.8% vs. 54.0%) during the pandemic. Patients with endometriosis and "significant" pelvic pain reported more concern and worsening than patients without "significant" pelvic pain, and evaluated the assistance received poorly. Multivariate analysis showed pelvic pain, limitation in usual activity, and sadness as risk factors of perception of disease worsening. Awaiting surgery and the feeling of sadness were risk factors of concern. Conclusions: Patients with endometriosis, and especially patients with "significant" pelvic pain, reported greater concern and the perception of worsening during the SARS-COV2 pandemic. Tele-health is a useful tool in patients with endometriosis, and face-to-face visit should be considered in those reporting "significant" pelvic pain. Clinical Trial Registration Number: HCB 1202011497.

Impact of Adenomyosis on Women's Psychological Health and Work Productivity: A Comparative Cross-Sectional Study.

Background: Quality of life in adenomyosis (AD) patients has been poorly investigated. Previous data suggest that AD has negative impact on the quality of life in these women. Materials and Methods: From September 2018 to December 2019, all consecutive female premenopausal patients aged ≥18 years diagnosed with AD by transvaginal ultrasound (TVU) were invited to participate in a comparative cross-sectional study. The Short Form-36-item (SF-36) health questionnaire and the Hospital Anxiety and Depression Scale (HADS) were administered. Work productivity and activity impairment were assessed using the Work Productivity and Activity Impairment Questionnaire: General Health version (WPAI:GH). Data obtained from these patients were compared with women with normal-appearing myometrium in the TVU recruited during routine gynecological visits. The study was approved by the Clinical Research Ethics Committee of the Hospital Clinic (reference HCB/2018/0919). Results: One hundred three patients with AD and 214 without AD were analyzed. Patients with AD compared to those without AD showed significantly lower scores in all domains of the SF-36 questionnaire and mean (SD) higher scores in the HADS questionnaire for anxiety (10.06 [3.04] vs. 6.92 [2.98], p < 0.001) and depression (6.39 [3.89] vs. 2.74 [2.01], p < 0.002). Significant differences (p < 0.001) were also found for the percentages of absenteeism (12.2% vs. 1.1%), presenteeism (31.1% vs. 11.4%), overall work productivity loss (38.2% vs. 12.4%), and activity impairment (55.7% vs. 9.9%). The presence of AD was associated with higher yearly estimated indirect costs of €5161.32 (€7928.0 vs. €2460.8, p < 0.001). Conclusions: AD negatively affects women's health-related quality of life, psychological health, and work productivity, with impairment at work and daily activities, and higher risk for anxiety and depression.

EQD2 Analyses of Vaginal Complications in Exclusive Brachytherapy for Postoperative Endometrial Carcinoma.

Background: To evaluate whether EQD2(α/ß = 3Gy) at 2 cm3 of the most exposed area of the vagina is related to late vaginal toxicity in postoperative endometrial cancer (PEC) patients (p) treated with exclusive brachytherapy (BT). Methods: From 2014 to 2017, 43p were included in this study. BT was administered: 3-fractions of 6Gy in 37p and 2-fractions of 7.5Gy in 6p. The dose was prescribed at a depth of 5 mm from the applicator surface with dose-point optimization based on distance. The active treatment length was 2.5 cm. CTV-D90 and the dose to the most exposed 2 cm3 of the vagina was calculated for each patient. Late toxicity of the bladder and rectum was assessed using Radiation Therapy Oncology Group (RTOG) criteria, and vaginal toxicity by objective Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA) (LENT-SOMA) criteria. Statistics: frequency tables, mean, median, range, standard deviation, and box plot. Results: The median follow-up was 51 months (12-68). 20 p (46.5%) and 2 p (4.7%) developed G1 and G2 vaginal complications, respectively. Only 1/2 p-G2 receiving EQD2(α/ß = 3Gy) at 2 cm3 >68Gy presented vaginal shortening and 18/20 p-G1 received doses < 68Gy. Conclusions: PECp receiving exclusive brachytherapy with doses < 68Gy EQD2(α/ß = 3Gy) at 2 cm2 of the vagina presented only G0-G1 vaginal toxicity, except for one with bleeding telangiectasias. Larger prospective studies are necessary to confirm the present results.

Number of paraaortic lymph node dissections as a prognostic factor in locally advanced cervical cancer.

BACKGROUND: 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. METHODS: We analyzed 78 patients with locally advanced cervical cancer that underwent complete paraaortic lymphadenectomy. RESULTS: Fifteen (19.2%) women had paraaortic LN metastases. The mean number of LN extracted was 11.1 (SD 7.5). Patients with paraaortic LN metastases presented a worse overall survival (127.1 months [95% CI 111.7-142.4] vs. 59.6 months [95% CI 31.2-87.9]; p<0.01). Nevertheless, there were no differences regarding disease-free survival. There were no prognostic differences according to the number of LNs resected in patients with negative lymphadenectomy. CONCLUSIONS: Patients with locally advanced cervical cancer and paraaortic LN metastases present worse survival. In women with negative paraaortic LN, the number of LNs removed does not imply shorter survival.

Perivascular epitheliod cell tumors: Study of three gynecological cases.

ANTECEDENTS: 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. PATIENTS AND METHODS: We contribute to literature with three gynecological cases; uterine, vaginal and retroperitoneal PEComas. RESULTS: The uterine and vaginal PEComa, have required surgical treatment, and are free of disease at 9 and 5 months respectively. The retroperitoneal PEComa has recurred at 72 months of follow-up in form of retroperitoneal mass and pulmonary lymphangioleomyomatosis, continues treatment with sirolimus with good tolerance and partial response. DISCUSSION: Given the scarcity of cases, the literature consists of case reports and mini-reviews. Some authors have categorized the PEComas based on prognostic factors, but there is no agreement regarding the follow-up and treatment. 18F-FDG-PET/CT can help characterize these lesions. The surgery is the standard. In recurrent or malignant cases, there is a lack of evidence regarding chemotherapy and radiotherapy. New therapies with inhibitory m-TOR open a hopeful therapeutic window.

Value of HPV 16/18 Genotyping and p16/Ki-67 Dual Staining to Predict Progression to HSIL/CIN2+ in Negative Cytologies From a Colposcopy Referral Population.

OBJECTIVES: To assess the prognostic value of human papillomavirus (HPV) 16/18 genotyping and p16/Ki-67 dual staining cytology in high-risk HPV (hrHPV)-positive women with no lesion or minor abnormalities. METHODS: We evaluated progression to high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grades 2 to 3 or cervical cancer (HSIL/CIN2+), persistence/regression of hrHPV infection in women referred to colposcopy showing hrHPV infection, histology diagnosis different from HSIL/CIN2+, and negative cytology. HPV 16/18 genotyping and dual staining were performed in liquid-based cytologic specimens obtained on the first visit. RESULTS: Progression was observed in 16 (8.0%) of 200 women. Those with HPV 16/18 infection had an increased risk of progression compared with women infected by other hrHPV types, and they also showed more persistence. However, no association was observed between progression or persistence and the result of the dual staining. CONCLUSIONS: HPV 16/18-positive women with no lesions or minor abnormalities are at high risk of progression to HSIL/CIN2+ and hrHPV persistence.