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Background: Human papillomavirus (HPV), a leading cause of cervical cancer, is present in most cases of the disease and ranks as the fourth most common cancer in women globally. Among the HPV types, fourteen (HPV 16/18/31/33/35/39/45/51/52/56/58/59/66/68) are recognized as high-risk (hrHPV), each with varying levels of oncogenic potential. Detecting and genotyping these hrHPV types in cervical lesions is crucial, requiring the development of new diagnostic methods., Methods: This study focuses on a retrospective analysis conducted on 44 women from the Cova da Beira Local Health Unit. We used the Anyplex™ II hrHPV Detection kit for hrHPV genotyping from paraffin-embedded cervical tissue samples., Results: hrHPV types were identified in 38 out of the 44 women. Genotyping revealed HPV-16 (55.3%), HPV-18/39/56/58/59 (5.3%), HPV-31 (21.1%), HPV-35 (7.9%), HPV-51/66 (2.6%), and HPV-52 (10.5%)., Conclusions: This study demonstrates that the Anyplex™ II hrHPV Detection kit, originally designed for cervical cancer screening, is also effective for hrHPV genotyping in histological analyses. This methodology offers a simpler and more cost-effective approach for cervical cancer risk stratification. Its implementation in clinical practice could enhance the detection of hrHPV in cervical lesions, thereby contributing to more precise diagnoses and potentially more informed treatment strategies.

Breast cancer remains the leading cause of cancer deaths for women. Long-term estrogen exposure is considered carcinogenic due to semiquinone production and to compromised detoxification. Metabolic regulator polymorphisms, such as KEAP1 (rs1048290) and NRF2 (rs35652124, rs6721961, rs6706649), can be valuable in understanding the individual cytoprotection profile. Thus, we aim to genotype these polymorphisms in blood, tumours and surrounding tissue, to identify somatic mutations and correlate it to prognoses. A total of 23 controls and 69 women with histological confirmed breast cancer were recruited, and DNA from blood/surrounding/tumour tissue was genotyped. Genotyping and clinicopathological data were correlated. We verified that rs35652124 presents different genotype distribution between the blood/surrounding tissue ( p -value = 0.023) and tumour/surrounding tissues ( p -value = 0.041). Apart from rs35652124 and considering the histological grade, the other four polymorphisms have different distributions among different tissues. There is a tendency towards the loss of heterozygosity in the surrounding tissue when compared to blood and tumour tissues, and higher genotype variability in histologic grade 2. These somatic mutations and different distribution patterns may indicate a heterogeneous and active microenvironment, influencing breast cancer outcome. Additionally, it would be pertinent to evaluate the predictive value of the histologic grade 2 considering somatic mutation profiles and distributions.

This study aims to clarify the effect of postmenopausal bilateral oophorectomy on plasma steroid hormone levels. Women who were submitted in the postmenopausal period to hysterectomy for uterine benign conditions were divided into two groups: 18 women had isolated hysterectomy and 11 had hysterectomy with bilateral salpingo-oophorectomy. In both groups serum hormone levels were quantified by solid phase extraction and gas chromatography and tandem mass spectrometry. Differences in dehydroepiandrosterone (DHEA), testosterone, androstenedione and oestradiol were determined in both groups. The analysis revealed lower steroid levels in the bilateral salpingo-oophorectomy group when compared to the isolated hysterectomy group with statistically significant differences found for DHEA (5.8 ± 3.2 vs. 9.4 ± 4.4 ng/mL; p  = 0.019) and oestradiol (0.69 ± 0.4 vs. 1.48 ± 4.3 ng/mL; p  = 0.007). The results are consistent with a significant endocrine activity of the postmenopausal ovary. The clinical consequences of these findings need to be clarified and postmenopausal prophylactic bilateral salpingo-oophorectomy re-evaluated.IMPACT STATEMENT What is already known on this subject? Although it is consensual that premenopausal prophylactic bilateral oophorectomy should not be performed because it has harmful effects on women's health, the evidence regarding the effects of postmenopausal prophylactic bilateral oophorectomy is scarce and this procedure continues to be a regular practice. Few studies have demonstrated that postmenopausal ovaries still have endocrine activity that may impact older women's health. What do the results of this study add? This is the first study to compare hormone levels of postmenopausal women based on their hysterectomy and oophorectomy status using GC-MS/MS, a highly sensitive bioanalytical assay for the measurement of steroid hormones. Previous studies relied on immunoassays and did not compare DHEA levels, which according to the intracrinology theory is a precursor for androgens and oestrogens. In this study, statistically significant lower levels of DHEA and oestradiol were found after postmenopausal bilateral salpingo-oophorectomy. What are the implications of these findings for clinical practice and/or further research? This is a pilot study that may lead to further investigation in this area to clarify the impact of the prophylactic removal of postmenopausal ovaries on older women's health and lead to changes in surgical procedures.

Cervical cancer is one of the most common types of cancer in women. Cervical cancer screening is needed for the detection and treatment of cervical neoplastic lesions that can evolve to neoplasia and to reduce the incidence of cervical cancer. Recently, changes were made to increase the efficiency of the screening process such as employing the human papilloma virus detection test as the gold standard for cervical cancer screening and acknowledging the importance of adapting clinical practice to consider the risk of developing this neoplasia. Considering this paradigm shift, new clinical practice guidelines are now needed. For this purpose, a group of experts analyzed and discussed the most recent literature, defining recommendations and proposing clinical practice guidelines that focus on risk stratification, diagnostic evaluation, and on the therapeutical approach and follow-up of women with altered screening results. The aim of this article is to guide clinical practice regarding actions to take in face of altered results of cervical cancer screening and, consequently, to improve the secondary prevention of this condition.

Previous studies using immunoassays for steroid measurements have focused on the association between steroid hormone levels and bone mineral density (BMD) in postmenopausal women, obtaining contradictory results. This study aimed to assess this association using a highly sensitive bioanalytical method. A total of 68 postmenopausal women, aged 65-89 years, were enrolled in a cross-sectional study. Measurements of the BMD of the hip and lumbar spine were performed using dual energy X-ray absorptiometry, and serum hormone levels were quantified by gas chromatography and tandem mass spectrometry. Associations between estradiol (E2), testosterone, dehydroepiandrosterone (DHEA), androstenedione and T score levels of the hip and lumbar spine were evaluated, after adjustment for confounding variables. The analysis revealed a statistically significant association between testosterone and the T score of the hip (p = 0.035), but not that of the lumbar spine. No statistically significant associations were found between E2, DHEA, androstenedione and the T scores of the hip and the lumbar spine. Using a highly sensitive hormone assay method, our study identified a significant association between testosterone and BMD of the hip in women over 65 years of age, suggesting that lower testosterone increases the risk of osteoporosis., (© 2023. The Author(s).)

At Portuguese-organized cervical cancer (CC) screening programs, all women testing positive for human papillomavirus (HPV) 16 and/or 18 are referred for immediate colposcopy. This study aimed to evaluate the utility of reflex cytology in women who test positive for HPV 16 and/or 18 to improve the efficiency of CC screening. A cross-sectional and retrospective study was performed based on data from the routine CC screening protocol in force at Cova da Beira University Hospital Center, Portugal between August 2012 and June 2021. The screening method was the Cobas 4800 HPV test using the liquid medium Surepath. In all the selected cases, the patient's HPV test results and the cytology and histology findings of the biopsies obtained using colposcopy were analyzed. This study included 339 women who first tested positive for HPV 16 and/or 18 and were referred for immediate colposcopy, in whom 40 (11.8%) cases of high-grade squamous intraepithelial lesion (HSIL+) were diagnosed. Of these, 12 (30%) had reflex cytology negative for intraepithelial lesion or malignancy (NILM) and 14 (35%) had HSIL+ cytology. After 3 years, 14 (9.3%) of the 150 women who were still undergoing follow-up were diagnosed with histologic HSIL+ lesions, of which 5 (35.7%) had baseline NILM cytology. Despite the small sample, the results of this study allow us to conclude that reflex cytology is not useful for discrimination to immediate referral for colposcopy in women who test positive for HPV 16 and/or 18, as most women with a histologic diagnosis of an HSIL+ lesion had

Cervical cancer is one of the most common cancers and is one of the major cause of deaths in women, especially in underdeveloped countries. The patients are usually treated with surgery, radiotherapy, and chemotherapy. However, these treatments can cause several side effects and may lead to infertility. Another concerning gynecologic cancer is endometrial cancer, in which a high number of patients present a poor prognosis with low survival rates. AS1411, a DNA aptamer, increases anticancer therapeutic selectivity, and through its conjugation with gold nanoparticles (AS1411-AuNPs) it is possible to improve the anticancer effects. Therefore, AS1411-AuNPs are potential drug carriers for selectively delivering therapeutic drugs to cervical cancer. In this work, we used AS1411-AuNPs as a carrier for an acridine orange derivative (C 8 ) or Imiquimod (IQ). The AS1411 aptamer was covalently bound to AuNPs, and each drug was associated via supramolecular assembly. The final nanoparticles presented suitable properties for pharmaceutical applications, such as small size, negative charge, and favorable drug release properties. Cellular uptake was characterized by confocal microscopy and flow cytometry, and effects on cellular viability were determined by MTT assay. The nanoparticles were then incorporated into a gel formulation of polyethylene glycol, suitable for topical application in the female genital tract. This gel showed promising tissue retention properties in Franz cells studies in the porcine vaginal epithelia. These findings suggest that the tested nanoparticles are promising drug carriers for cervical cancer therapy.

Objectives: The aims of the study were to assess the available literature concerning the indications, performance, technique, and classification of wet mount microscopy (WMM) and to establish evidence-based recommendations., Methods: Literature review from the main scientific databases was performed by the ad hoc "Vaginitis and Microbiome Committee" of the International Society for the Study of Vulvovaginal Disease. The document was approved by the executive council and membership of the International Society for the Study of Vulvovaginal Disease., Results: Available data are limited and usually of low level of evidence. Nevertheless, it shows that WMM is capable of reducing misdiagnosis, overtreatment, and undertreatment of vaginal conditions. It has an excellent performance for the diagnosis of bacterial vaginosis and variable performance for trichomoniasis and candidiasis. It is the gold standard for aerobic vaginitis/desquamative inflammatory vaginitis. Currently, there is no recommendation to use WMM in the screening of asymptomatic women.The use of phase contrast is recommended to improve performance and reproducibility. Sampling location, devices, and technique have an impact on the results.Available scoring and classification scores have significant limitations., Conclusions: Wet mount microscopy is a point-of-care, inexpensive, and fast technique that, with practice, can be mastered by office clinicians. It should be considered a basic skill in the curricula of gynecology and obstetrics residencies. Recommendations are provided on sampling, reading, and scoring., Competing Interests: P.V.B. was an investigator for Seegene and received speaker fees from Seegene, Merck, Gedeon-Richter, and Roche. The other authors have declared they have no conflicts of interest., (Copyright © 2021, ASCCP.)

Estrogen metabolism plays an important role in tumor initiation and development. Lifetime exposure to high estrogens levels and deregulation of enzymes involved in estrogen biosynthetic and metabolic pathway are considered risk factors for breast cancer. The present study aimed to evaluate the impact of mutations acquisition during the lifetime in low penetrance genes that codify enzymes responsible for estrogen detoxification. Genotype analysis of GSTM1 and GSTT1 null polymorphisms, CYP1B1 Val432Leu and MTHFR C677T polymorphisms was performed in 157 samples of women with hormone-dependent breast cancer and correlated with the age at diagnosis. The majority of patients with GSTT1 null genotype and with both GSTM1 and GSTT1 null genotypes were 50 years old or more at the diagnosis ( p -value = 0.021 and 0.018, respectively). Older women with GSTM1 null genotype were also carriers of the CYP1B1 Val allele ( p -value = 0.012). As well, GSTT1 null and CYP1B1 Val genotypes were correlated with diagnosis at later ages ( p -value = 0.022). Similar results were found associating MTHFR C677T and GSTT1 null polymorphism ( p -value = 0.034). Our results suggest that estrogen metabolic pathway polymorphisms constitute a factor to be considered simultaneously with models for breast cancer risk assessment.

Background: Cardiotoxicity is a known complication and one of the most adverse effects from the use of conventional treatments such as anthracyclines and trastuzumab in breast cancer (BC) care. This phenomenon has been associated with the restriction of therapeutic options and the increase of cardiovascular complications, which may compromise the survival of patients. Implementation of preventive strategies is an important approach for the management of this issue. Physical exercise has been proposed as a non-pharmacological strategy to counteracting cardiotoxicity. The aim of this protocol is to describe the rationale and methods for a systematic review of published randomized controlled trials (RCTs) that have analysed the effects of physical exercise on outcomes of cardiac (dys)function in women with BC undergoing neoadjuvant or adjuvant treatment containing anthracyclines and/or trastuzumab., Methods and Analysis: This is a protocol for a systematic review reported according to the PRISMA-P 2015 checklist. Randomized controlled trials (RCTs) will be included. The literature will be screened on MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, ISI Web of Science and Scopus. The risk of bias of the included RCTs will be assessed using the Cochrane Collaboration's tool. The primary outcomes will be systolic function (left ventricular ejection fraction), diastolic function (E/A' ratio, deceleration time of early left ventricular filling, isovolumetric relaxation time, E/E' septal and lateral ratio) and myocardial deformation imaging outcomes (strain and strain rate [measured in longitudinal, radial, or circumferential directions]). Secondary outcomes will be cardiac biomarkers (troponin I or T, high-sensitivity troponin I or T, brain natriuretic peptide, amino terminal of B-type natriuretic peptide). Data will be descriptively reported, and quantitative synthesis will also be considered if the included studies are sufficiently homogenous., Discussion: This systematic review will help to understand the effectiveness of physical exercise on counteracting cardiotoxicity related to anticancer therapies in women with BC., Systematic Review Registration: PROSPERO CRD42018096060.

After breast cancer diagnosis (BCD), localized breast cancer (BC) patients are treated with curative intent by several therapeutic modalities. Despite the benefit of those therapies, the induction of side effects is acommon consequence affecting psychosocial and physiological outcomes. This quasi-experimental study compared physical fitness in recent-term (14-30 months; n= 11) and later-term (74-92 months; n= 8) BCD patients. After inclusion, recent-term BCD patients were engaged in asupervised exercise program and was explored its impact on physical fitness, health-related quality of life (HR-QOL) and fatigue. At baseline (M1) and after 8 (M2) and 16 weeks (M3) of this period, HR-QOL and fatigue were evaluated by the EORTC QLQ-C30 questionnaire and physical fitness through the estimation of maximum oxygen consumption (VO2max,ml.kg.min-1), handgrip force (kg) and sit-stand test. At baseline, women with later-term BCD have revealed better VO2max (p < 0.05) than recent-term BCD patients. There was asignificant time*group interaction for physical fitness outcomes and only the patients who have participated in the exercise program reported significant changes between baseline and at 16 weeks. The observed results demonstrated that performing regular exercise is associated with effective psychosocial and physiological recovery after BCD.

Objective  To assess the medical doctors and medical students' opinion regarding the evidence and ethical background of the performance of vulvovaginal aesthetic procedures (VVAPs). Methods  Cross-sectional online survey among 664 Portuguese medical doctors and students. Results  Most participants considered that there is never or there rarely is a medical reason to perform: vulvar whitening (85.9% [502/584]); hymenoplasty (72.0% [437/607]); mons pubis liposuction (71.6% [426/595]); "G-spot" augmentation (71.0% [409/576]); labia majora augmentation (66.3% [390/588]); labia minora augmentation (58.3% [326/559]); or laser vaginal tightening (52.3% [313/599]). Gynecologists and specialists were more likely to consider that there are no medical reasons to perform VVAPs; the opposite was true for plastic surgeons and students/residents.Hymenoplasty raised ethical doubts in 51.1% (283/554) of the participants. Plastic surgeons and students/residents were less likely to raise ethical objections, while the opposite was true for gynecologists and specialists.Most considered that VVAPs could contribute to an improvement in self-esteem (92.3% [613/664]); sexual function (78.5% [521/664]); vaginal atrophy (69.9% [464/664]); quality of life (66.3% [440/664]); and sexual pain (61.4% [408/664]). Conclusions  While medical doctors and students acknowledge the lack of evidence and scientific support for the performance of VVAPs, most do not raise ethical objections about them, especially if they are students or plastic surgeons, or if they have had or have considered having plastic surgery., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)

Estrogen receptor alpha (ERα), that mediates the biologic effects of estrogen in estrogen-sensitive tissues like breast, is genetically polymorphic. To evaluate the association between -397 PvuII (T>C) and -351 XbaI (A>G) restriction fragment length polymorphisms (RFLPs) in intron 1 of ERα gene and susceptibility of breast cancer, we undertook a case-control study in BRCA1 185delAG and 5382insC/BRCA2 6174delT negative Portuguese women. The study population consisted of 107 patients with histological diagnosis of breast cancer and 121 women with no history of breast cancer. Genomic DNA was extracted from blood samples and genotyping analyses were performed by PCR-RFLP. XbaI polymorphism was associated with a significant reduced risk of breast cancer for carriers of the x allele in homozygozity (OR 0.178; 95% CI 0.070-0.456; P<0.001) or heterozigozity (OR 0.223; 95% CI 0.089-0.561; P=0.001). The PvuII polymorphism was associated with a non-significantly reduced risk. The combined analysis of PvuII and XbaI polymorphisms revealed none synergistic effect of the two genotypes, except for simultaneous carriers of pp and xx genotypes, that have a reduced risk of breast cancer (OR 0.226; 95% CI 0.049-1.035; P=0.044). The combination of PvuII and XbaI genotypes into haplotypes showed that carriers of two copies of the px (ppxx) haplotype had a reduced risk of breast cancer (OR 0.405; 95% CI 0.194-0.843; P=0.014), compared with PX (PPXX+PPXx+PpXX+PpXx) haplotypes. PvuII and XbaI polymorphisms were in linkage disequilibrium both in cases (D=0.044, r2=0.049, X2=5.216, P=0.022) and controls (D=0.090, r2=0.139, X2=16.819, P<0.001), but not in the entire sample population analyzed as a whole (D=0.087, r2=0.0076, X2=1.733, P=0.188). In conclusion, in this case-control study we found that ERα gene XbaI polymorphism may modify individual susceptibility for breast cancer in this population.

A 61-year-old woman presented to the emergency room complaining of anterior left thoracic pain and shortness of breath even after minor efforts. Her previous medical history was unremarkable. Pulmonary angiographic tomography showed a moderate bilateral pleural effusion that had collapsed inferior lung lobes, a large pericardial effusion, and several enlarged lymph nodes in the anterior mediastinum. Echocardiogram (ECG) showed a considerable pericardial effusion with some degree of heart function impairment. Pericardiocentesis and thoracocentesis revealed neoplastic cells in both pericardial and pleural fluids. Abdominal and pelvic ultrasound showed a complex cystic mass with a 13-cm diameter located at left adnexal region and another complex cystic tumor with five-cm diameter at right adnexal region, with small amount of peritoneal effusion. Surgical staging was performed. Pathologic diagnosis was primitive left fallopian tube serous adenocarcinoma with peritubal involvement and multiple peritoneal and lymphatic metastases (FIGO Stage IV; TNM pT3c M1). Chemotherapy was initiated. Death occurred 25 months after diagnosis, with secondary dissemination (breast and lung). No recurrence of pericardial effusion was registered after chemotherapy, suggesting a high susceptibility of pericardial metastasis.

Background: In breast cancer cyclooxygenase-2 overexpression is related with poor outcomes, but the clinical relevance of cyclooxygenase-2 is still unclear. Progesterone receptor is a regulator of cyclooxygenase-2 expression. We postulate that progesterone receptor was associated to cyclooxygenase-2 expression and clinicopathologic factors in breast cancer., Methods: Cyclooxygenase-2 and progesterone receptor expression was analyzed, by immunohistochemistry, in 31 cases of invasive ductal carcinoma., Results: The expression of cyclooxygenase-2 and progesterone receptor was observed in 64.5% and 45.2% of the tumors, respectively. We found 11 tumors with both cyclooxygenase-2 and progesterone receptor overexpression and they are related with tumor lower size and lower axillary node metastasis., Conclusion: These results suggest that progesterone receptor has a protective role in breast cancer by inhibiting chronic inflammatory pathway., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To evaluate clinical prognostic factors for local recurrence of vulvar squamous cell carcinoma after primary surgical treatment., Study Design: Of 104 patients treated for squamous cell carcinoma of the vulva in an 11-year period (1987-1997) at the Portuguese Cancer Institute, we selected for study 56 patients who meet the following criteria: (1) International Federation of Gynecology and Obstetrics (FIGO) stage Ib-IVa, (2) primary treatment of en bloc radical vulvectomy and bilateral groin dissection, and (3) follow-up reports. Files were retrieved for retrospective analysis. Fifteen patients (26.8%) had local recurrence at the fifth year. At the 24th month, 11 patients had local recurrence, and 31 were in follow-up, without recurrence. We evaluated age at initial diagnosis, date of surgical treatment, tumor size, results of tumor macroscopy, histologic differentiation, groin lymph node status, FIGO stage, resection limits, adjuvant radiotherapy, duration of stay, associated vulvar skin disease, date of detection of recurrence, site/sites of recurrence and follow-up status at the 24th month after surgical treatment between the 11 patients with local recurrence and 31 in follow-up without recurrence., Results: The 11 patients with local recurrence had a significant initial FIGO stage, IVa (P = .049) and a significant association with the number of groin lymph nodes containing metastasis in comparison to the 31 patients without local recurrence. No other statistically compared data were significant., Conclusion: These results suggest that vulvar squamous cell carcinoma local recurrence after a primary surgical procedure is related to poor tumor prognostic factors (number of groin nodes containing tumor metastasis and FIGO stage IVa). On multivariate analysis, the presence of metastasis in two or more groin nodes was a powerful factor related to local recurrence. Postoperative radiotherapy to the vulva for such patients with a high risk of local recurrence is advisable.