HPV testing for cervical cancer screening: Should reflex cytology be performed after a positive test for HPV 16 and 18?

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

Steroid hormone levels and bone mineral density in women over 65 years of age.

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.

[Consensus Guidelines for the Management of Abnormal Cervical Cancer Screening Tests by the SPCPTGI]. / Orientações de Consenso para a Abordagem dos Resultados Alterados nos Testes de Rastreio do Cancro do Colo do Útero pela SPCPTGI.

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.

O cancro do colo do útero (CCU) é globalmente um dos tipos de cancro mais comum em mulheres. O rastreio do CCU é indispensável para a deteção e tratamento de lesões neoplásicas cervicais que possam evoluir para neoplasia, com o objectivo de reduzir a incidência deste cancro. Nos últimos anos, têm ocorrido alterações que visam o aumento da eficácia do rastreio. Nomeadamente, o uso de teste de deteção do vírus do papiloma humano como método de rastreio primário do CCU e a valorização da importância de adaptar a prática clínica em função do risco de desenvolvimento do CCU. Desta forma, são necessárias novas normas de atuação clínica, que contemplem esta mudança de paradigma. Assim, um grupo de especialistas analisou e discutiu a literatura mais recente, definindo recomendações e propondo normas de prática clínica que se focam na estratificação de risco, avaliação diagnóstica, e na conduta terapêutica e de seguimento de mulheres com resultados dos testes de rastreio alterados. Este trabalho tem como objetivo facilitar a prática clínica em resposta a resultados alterados nos testes e, consequentemente, melhorar a prevenção secundária do CCU.

Steroid hormone levels in postmenopausal hysterectomised women with and without ovarian conservation: the continuous endocrine function of the ovaries.

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 STATEMENTWhat 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.

Aptamer-Functionalized Gold Nanoparticles for Drug Delivery to Gynecological Carcinoma Cells.

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 (C8) 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.

The International Society for the Study of Vulvovaginal Disease Vaginal Wet Mount Microscopy Guidelines: How to Perform, Applications, and Interpretation.

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.

Influence of Estrogenic Metabolic Pathway Genes Polymorphisms on Postmenopausal Breast Cancer Risk.

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 CYP1B1Val allele (p-value = 0.012). As well, GSTT1 null and CYP1B1Val 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.

Effects of physical exercise on outcomes of cardiac (dys)function in women with breast cancer undergoing anthracycline or trastuzumab treatment: study protocol for a systematic review.

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.

Health-related quality of life and physical fitness in breast cancer patients: the impact of a supervised physical exercise program in women with no exercise experience.

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.

Survey on Aesthetic Vulvovaginal Procedures: What do Portuguese Doctors and Medical Students Think? / Inquérito sobre procedimentos estéticos vulvovaginais: qual a opinião dos médicos e estudantes de medicina portugueses?

Abstract Objective To assess themedical doctors andmedical 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 amedical 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 specialistsweremore likely to consider that there are no medical reasons to performVVAPs; 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.

Resumo Objetivos Avaliar a opinião de médicos e estudantes de medicina relativamente à evidência e contexto ético para a realização de procedimentos estéticos vulvovaginais (PEVVs). Métodos Estudo transversal, consistindo de inquérito online a 664 médicos e estudantes de medicina portugueses. Resultados A maioria dos participantes considerou que nunca ou raramente há uma razão médica para a realização de: branqueamento vulvar (85,9% [502/584]); himenoplastia (72,0% [437/607]); lipoaspiração do mons pubis (71,6% [426/595]); aumento do "ponto G" (71,0% [409/576]); aumento dos grandes lábios (66,3% [390/588]); aumento dos pequenos lábios (58,3% [326/559]) ou aperto vaginal com laser (52,3% [313/599]). Ser ginecologista e especialista associou-se a maior probabilidade de considerar não haver razões médicas para a realização de PEVV; o oposto foi verdade para os cirurgiões plásticos e estudantes/internos. A himenoplastia levantou dúvidas em termos éticos em 51,1% (283/554) dos participantes. Cirurgiões plásticos e estudantes/internos relatarammenos dúvidas emtermos éticos; o oposto foi verdade para os ginecologistas ou especialistas. Amaioria considerou que os PEVVs podemcontribuir para uma melhoria na autoestima (92,3% [613/664]); função sexual (78,5% [521/664]); atrofia vaginal (69,9% [464/664]); qualidade de vida (66,3% [440/664]); e dor sexual (61,4% [408/664]). Conclusões Ainda que os médicos e estudantes de medicina reconheçam a falta de evidência e bases científicas para a realização de PEVVs, a maioria não levanta objecções em termos éticos, especialmente se forem estudantes, cirurgiões plásticos, ou se eles próprios tiverem sido submetidos a cirurgia plástica ou considerem vir a sê-lo.

Survey on Aesthetic Vulvovaginal Procedures: What do Portuguese Doctors and Medical Students Think?

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.

Objetivos Avaliar a opinião de médicos e estudantes de medicina relativamente à evidência e contexto ético para a realização de procedimentos estéticos vulvovaginais (PEVVs). Métodos Estudo transversal, consistindo de inquérito online a 664 médicos e estudantes de medicina portugueses. Resultados A maioria dos participantes considerou que nunca ou raramente há uma razão médica para a realização de: branqueamento vulvar (85,9% [502/584]); himenoplastia (72,0% [437/607]); lipoaspiração do mons pubis (71,6% [426/595]); aumento do "ponto G" (71,0% [409/576]); aumento dos grandes lábios (66,3% [390/588]); aumento dos pequenos lábios (58,3% [326/559]) ou aperto vaginal com laser (52,3% [313/599]). Ser ginecologista e especialista associou-se a maior probabilidade de considerar não haver razões médicas para a realização de PEVV; o oposto foi verdade para os cirurgiões plásticos e estudantes/internos.A himenoplastia levantou dúvidas em termos éticos em 51,1% (283/554) dos participantes. Cirurgiões plásticos e estudantes/internos relataram menos dúvidas em termos éticos; o oposto foi verdade para os ginecologistas ou especialistas.A maioria considerou que os PEVVs podem contribuir para uma melhoria na autoestima (92,3% [613/664]); função sexual (78,5% [521/664]); atrofia vaginal (69,9% [464/664]); qualidade de vida (66,3% [440/664]); e dor sexual (61,4% [408/664]). Conclusões Ainda que os médicos e estudantes de medicina reconheçam a falta de evidência e bases científicas para a realização de PEVVs, a maioria não levanta objecções em termos éticos, especialmente se forem estudantes, cirurgiões plásticos, ou se eles próprios tiverem sido submetidos a cirurgia plástica ou considerem vir a sê-lo.

Abnormal uterine bleeding as a presenting symptom is related to multiple uterine leiomyoma: an ultrasound-based study.

PURPOSE: To determine the prevalence of uterine leiomyomas, diagnosed by ultrasound, in a private health care setting located in the central eastern region of Portugal, and to explore the demographic and clinical factors related to diagnosis and symptomatology. PATIENTS AND METHODS: The files of 624 patients attending a private clinic in Covilhã, Portugal, from January 2 to December 31, 2010 were retrieved for evaluation. Pelvic ultrasound record, age, weight, height, age at menarche, number of pregnancies and deliveries, marital status, menstrual cycles characteristic, and contraceptive method at consultation were included in the analysis. RESULTS: Uterine leiomyoma (UL) was diagnosed by ultrasonography in 161 (25.8%) patients. A single UL was diagnosed in 80 (49.7%) patients. In 79 (49.1%) patients, the largest leiomyoma had a dimension <20 mm. Prevalence of UL was age dependent: at 11.0% for women 20-39 years old; 45.4% for those aged 40-59 years; and 19.5% for women 60 years or older. Metrorrhagia was the most distressing presenting symptom. When menorrhagia was the presenting symptom, the probability of having an ultrasound diagnosis of UL was 73.3%. Metrorrhagia or menorrhagia, as presenting symptom, was significantly related to the ultrasound diagnosis of multiple ULs. CONCLUSION: UL was especially prevalent in women aged between 40 and 59 years. Patients with multiple ULs had significantly more abnormal uterine bleeding. In patients with menorrhagia or metrorrhagia, special attention should be taken in searching for the presence of multiple ULs during ultrasound.

Positive association of polymorphisms in estrogen biosynthesis gene, CYP19A1, and metabolism, GST, in breast cancer susceptibility.

PURPOSE: This case-control study was conducted in order to evaluate the potential role of polymorphic genes encoding enzymes involved in estrogen biosynthesis (CYP19A1) and metabolism (GSTM1, GSTT1, and GSTP1), and their action in modulating individual susceptibility to breast cancer. METHODS: Genomic DNA was extracted from blood samples of 101 patients with histological diagnosis of breast cancer and 121 healthy women. Genotyping analyses of CYP19A1 codon 39 Trp/Arg (T/C), GSTM1 and GSTT1 homozygous deletions, and GSTP1 codon 105 Ile/Val (A/G) were performed by polymerase chain reaction-based methods. RESULTS: Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression. Significant statistical association of the TC/CC genotypes combined with breast cancer risk was found, with reference to TT genotype (OR=1.770; 95% CI=1.036-3.024; p=0.036). Also, CYP19A1 arginine allele in homozygosity or heterozygosity (TC/CC) was associated with a significant increased risk for breast cancer when associated to GSTM1 null genotype (OR=6.158; 95% CI=2.676-14.171; p<0.001) and GSTT1 null genotype (OR=4.870; 95% CI=2.216-10.700; p<0.001). The three-way combination of CYP19A1 TC/CC, GSTM1 null, and GSTT1 null polymorphism was related with significant increased risk for breast cancer (OR=11.429; 95% CI=3.590-36.385; p<0.001). Valine alleles compared with isoleucine alleles in codon 105 in GSTP1, in combination with CYP19A1 genotypes, were not associated with an increase of breast cancer development. CONCLUSIONS: Our results suggest that the effect of CYP19A1 T/C polymorphism in susceptibility to breast cancer development can be modulated by the presence of GSTM1 and GSTT1, but not GSTP1.

Cyclooxygenase-2 immunoexpression in breast cancer: progesterone receptor influence.

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.

Smoking and cervical cancer.

Cervical cancer (CC) is the third most common cancer in women worldwide; however, CC is a preventable disease, and much effort should be done to prevent it. Persistence of high-risk HPV infection is the strongest epidemiologic risk factor for CC, however it is not sufficient for development of the disease it cofactors should be present. In 2004; IARC listed cervical cancer among those causally related to smoking. Smoking interferes with incidence and prevalence of HPV infection and is associated with cervical intraepithelial neoplasia and invasive CC. Multiple factors seem to intervene on cervical carcinogenesis related with tobacco, especially by direct local carcinogenic effect and local immunosuppression. Smoking addition is also closely related with other confounding factors, like unfavorable psychosocial events, systemic immunity, contraception, and nutrition, which got difficult epidemiologic evaluation of smoking role on cervical carcinogenesis. Smoking habits should be taken in account in clinical practice and in research concerning CC.

Glutathione S-transferase M1, T1, and P1 genotypes and breast cancer risk: a study in a Portuguese population.

Glutathione S-transferases are a superfamily of multifunctional enzymes that play a key role in Phase II metabolism, detoxifying therapeutic drugs, and various carcinogens by conjugation with glutathione. We undertook a case-control study in Central-Eastern Portuguese population to evaluate the association of null genotype in GSTM1 and GSTT1 along with the polymorphism in GSTP1 (A/G) and susceptibility to breast cancer. The population sample consisted of 85 patients with histological diagnosis of breast cancer and 102 healthy women. Genomic DNA was extracted from blood samples, and genotyping analyses were performed by PCR-based methods. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression. We found a increased breast cancer risk associated with GSTM1 null genotype (OR = 3.597; 95% CI = 1.849-6.999; P = 0.0001) and GSTT1 (OR = 2.592; 95% CI = 1.432-4.690; P = 0.002), but the presence of valine alleles compared to isoleucine alleles in codon 105 in GSTP1 did not increase the risk of breast cancer development. The two-way combination of GSTM1 and GTTT1 null genotypes resulted in 8-fold increase for breast cancer risk (OR = 8.287; 95% CI = 3.124-21.980; P = 0.0001) and the three-way combination of GSTP1 105AA/AG and null genotypes for both GSTM1 and GSTT1 resulted in 5-fold increase for breast cancer risk (OR = 5.040; 95% CI = 1.392-18.248; P = 0.016). Our results suggest that GSTM1 and GSTT1 null genotype alone, both combined or combined with GSTP1 valine alleles, are associated with higher susceptibility to breast cancer development.

Neoplasia intraepitelial vulvar: um problema atual / Vulvar intraepithelial neoplasia: a current problem

A neoplasia intraepitelial da vulva (VIN) é uma denominação que foi introduzida incialmente pela International Society for Study of Vulvo-vaginal Diseases (ISSVD) e reconhecida posteriormente pela International Society of Gynaecological Pathology (ISGYP) e Organização Mundial da Saúde. É uma entidade patológica a que correspondem as VIN de tipo usual (verrucoso, basalióide e misto) e as VIN de tipo diferenciado. A incidência das lesões de VIN tem aumentado progressivamente, principalmente em mulheres jovens. A infecção pelo papilomavírus humano (HPV) de alto risco, pelo vírus da imunodeficiência humana (HIV), o tabagismo e a neoplasia intraepitelial do colo do útero, da vagina e região anal são factores de risco estabelecidos para as VIN. Não existem sintomas e sinais característicos das VIN, mas a doença se traduz sempre por lesões clinicamente identificáveis. A biópsia com o auxílio do colposcópio permite o diagnóstico. O tratamento da doença está sempre justificado pelo elevado risco de progressão para cancro invasivo. A excisão alargada das lesões ou a sua destruição com laser CO2 têm sido os métodos mais populares de tratamento. Independentemente do método terapêutico utilizado, as taxas de recidiva são elevadas, pelo que está aconselhada a vigilância apertada das doentes após tratamento. A terapêutica tópica com imiquimod se afigura promissora no tratamento das VIN. As vacinas profiláticas contra os tipos de HPV de alto risco prometem se tornar armas poderosas na prevenção primária da doença.

Vulvar intraepithelial neoplasia (VIN) is a pathological denomination coined by the International Society for Study of Vulvo-vaginal Diseases (ISSVD) and adopted by the International Society of Gynaecological Pathology (ISGYP) and by the World Health Organization. VIN is a heterogeneous pathological entity with a usual type (warty, basaloid and mixed) and a differentiated type. The incidence of the disease is increasing, especially in young women. The high-risk human papilomavirus (HR-HPV) infection, human immunodeficiency virus (HIV) infection, smoking, cervical, vaginal and rectal intraepithelial neoplasia are considered to be high risk factors for development of VIN. There are no specific symptoms or vulvar macroscopic aspects of VIN. However, a clinical lesion is always present. Liberal vulvar biopsies under colposcopy guidance should be done. Patients with diagnosis of VIN harbor an increased risk for vulvar invasive cancer. Surgical excision and laser CO2 vaporization are the most popular therapeutic modalities for VIN treatment, both with high rates of recurrence. A close follow-up of the patients is advised. Topical imiquimod seems to be a promising treatment option. Probably, prophylactic vaccination against HR-HPV will be an important tool for VIN prevention.

[Vulvar intraepithelial neoplasia: a current problem]. / Neoplasia intraepitelial vulvar: um problema atual.

Vulvar intraepithelial neoplasia (VIN) is a pathological denomination coined by the International Society for Study of Vulvo-vaginal Diseases (ISSVD) and adopted by the International Society of Gynaecological Pathology (ISGYP) and by the World Health Organization. VIN is a heterogeneous pathological entity with a usual type (warty, basaloid and mixed) and a differentiated type. The incidence of the disease is increasing, especially in young women. The high-risk human papillomavirus (HR-HPV) infection, human immunodeficiency virus (HIV) infection, smoking, cervical, vaginal and rectal intraepithelial neoplasia are considered to be high risk factors for development of VIN. There are no specific symptoms or vulvar macroscopic aspects of VIN. However, a clinical lesion is always present. Liberal vulvar biopsies under colposcopy guidance should be done. Patients with diagnosis of VIN harbor an increased risk for vulvar invasive cancer. Surgical excision and laser CO2 vaporization are the most popular therapeutic modalities for VIN treatment, both with high rates of recurrence. A close follow-up of the patients is advised. Topical imiquimod seems to be a promising treatment option. Probably, prophylactic vaccination against HR-HPV will be an important tool for VIN prevention.