Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics

Study of 138 vulvar lichen sclerosus patients and the malignant risk transformation

To report the prevalence of malignant transformation of vulvar lichen sclerosus (VLS) and possible risk factors. This is a cohort study with data analysis from medical records of 138 patients with histological diagnosis of VLS registered at the Vulvar Pathology Outpatient Clinic of the University Hospital, between 2007 and 2017. Predominance of risk factors was performed using logistic regression analysis. The variables studied were the length of follow-up, age, regular or irregular follow up; presence of symptoms (dyspareunia, pruritus and/or vulvar burning); histology characteristics, the presence of epithelial hyperplasia; and the presence of autoimmune diseases. There were 138 patients included in the study, and among them five progressed to malignant transformation. The patients had a median age of 59 years and 83% were symptomatic. The most frequent symptom was itching with 72%. Autoimmune diseases were present in 11.6%, the most prevalent being thyroid disease. All five case of malignant transformation (0.6%) had an irregular follow up. The logistic regression analysis was used among the studied variables, and no statistical significance was found among them (p ≥ 0.05). The relationship between hyperplasia and the clinical outcome of malignant transformation, in which non-significant but acceptable p value close to 0.05 was observed. The prevalence of malignant transformation in patients with VLS was 0.6%, and common factors were the lack of adherence to medical treatments and the loss of follow-up.

Residual Disease after Operative Hysteroscopy in Patients with Endometrioid Endometrial Cancer Associated with Polyps

Abstract Objective To evaluate the presence of residual disease in the uterine specimen after hysteroscopic polypectomy or polyp biopsy in patients with endometrioid endometrial cancer (EC). Methods We analyzed a series of 104 patients (92 cases from the Hospital AC Camargo and 12 from the Hospital do Servidor Público Estadual de São Paulo) with polyps that were diagnosed by hysteroscopy, showing endometrioid EC associated with the polyp or in the final pathological specimen. Patients underwent a surgical approach for endometrial cancer from January 2002 to January 2017. Their clinical and pathological data were retrospectively retrieved from the medical records. Results In 78 cases (75%), the polyp had EC, and in 40 (38.5%), it was restricted to the polyp, without endometrial involvement. The pathologic stage was IA in 96 cases (92.3%) and 90 (86.5%) had histologic grade 1 or 2. In 18 cases (17.3%), there was no residual disease in the final uterine specimen, but only in 9 of them the hysteroscopy suggested that the tumor was restricted to the polyp. In 5 cases (4.8%) from the group without disease outside of the polyp during hysteroscopy, myometrial invasion was noted in the final uterine specimen. This finding suggests the possibility of disease extrapolation through the base of the polyp. Conclusion Patients with endometrioid EC associated with polyps may have the tumor completely removed during hysteroscopy, but the variables shown in the present study could not safely predict which patient would have no residual disease.

Clinical Characteristics and Outcomes of a High-grade Endometrial Cancer Cohort Treated at Instituto Nacional de Câncer, Brazil

Abstract Objective To analyze the outcomes of a cohort of patients with high-risk histologies of endometrial cancer (EC) treated at Instituto Nacional de Câncer (National Cancer Institute, INCA, in Portuguese), in Brazil. Materials and Methods We reviewed the medical records of patients with high-risk histologies of EC in any stage registered at INCA between 2010 and 2016 to perform a clinical and demographic descriptive analysis and to evaluate the outcomes in terms of recurrence and survival. Results From 2010 to 2016, 2,145 EC patients were registered and treated at INCA, and 466 had high-grade histologies that met the inclusion criteria. The mean age of the patients was 65 years, 44.6% were Caucasian, and 90% had a performance status of 0 or 1. The most common histology was high-grade endometrioid (31.1%), followed by serous carcinoma (25.3%), mixed (20.0%), carcinosarcoma (13.5%), and clear cell carcinoma (9.4%). Considering the 2018 Fédération Internationale de Gynécologie et d'Obstétrique (International Federation of Gynecology and Obstetrics, FIGO, in French) staging system, 44.8%, 12.4%, 29.8%, and 12.9% of the patient were in stages I, II, III or IV respectively. Age (> 60 years), more than 50% of myoinvasion, higher stage, poor performance status, serous and carcinosarcoma histologies, and adjuvant treatment were independent factors associated with recurrence-free survival (RFS) and overall survival (OS) in the multivariate analysis. Conclusion The current findings reinforced the international data showing poor outcomes of these tumors, especially for serous and carcinosarcomas and tumors with advanced stages, with shorter survival and high recurrence rates in distant sites, independently of the FIGO stage. Adjuvant therapy was associated with better survival.

Assessment of Preoperative Endometrial Histopathological Sampling as a Predictor of Final Surgical Pathology in Endometrial Cancer

Abstract Objective To evaluate the agreement between the histopathological diagnoses of preoperative endometrial samples and surgical specimens and correlate the agreement between the diagnoses with the impact on surgical management and the survival of patients with endometrial adenocarcinomas. Methods Sixty-two patients treated for endometrial cancer at a university hospital from 2002 to 2011 were retrospectively evaluated. The histopathological findings of preoperative endometrial samples and of surgical specimens were analyzed. The patients were subjected to hysterectomy as well as adjuvant treatment, if necessary, and clinical follow-up, according to the institutional protocol. Lesions were classified as endometrioid tumor (type 1) grades 1, 2, or 3 or non-endometrioid carcinoma (type 2). Results The agreement between the histopathological diagnoses based on preoperative endometrial samples and surgical specimens was fair (Kappa: 0.40; p < 0.001). However, the agreement was very significant for tumor type and grade, in which a higher concordance occurred at a higher grade. The percentage of patients with lymph nodes affected was 19.2%. Although most patients presenting with disease remission or cure were in the early stages (90.5%), there were no significant differences between those patients who had a misdiagnosis (11/16; 68.8%) and those who had a correct diagnosis (25/33; 75.8%) based on preoperative endometrial sampling (p = 0.605). Conclusion Our findings corroborate the literature and confirm the under staging of preoperative endometrial samples based on histopathological assessment, especially for lower grade endometrial tumors. We suggest that the preoperative diagnosis should be complemented with other methods to better plan the surgical management strategy.

Sentinel Lymph Node Biopsy in Endometrial Cancer – A Systematic Review and Quality Assessment of Meta-Analyses

Abstract Objective To assess the quality of recent meta-analyses reviewing the diagnostic utility of sentinel node biopsy in endometrial cancer. Methods With the MeSH terms endometrial neoplasms and sentinel lymph node biopsy, PubMed and Embase databases were searched on October 21, 2020, and again on November 10, 2021, with meta-analysis and publication date filters set to since 2015. The articles included were classified with the A Measurement Tool to Assess Systematic Reviews (AMSTAR 2) assessment tool. Results The database searches found 17, 7 of which, after the screening, were selected for full review by the author, finally extracting six meta-analyzes for quality analysis. The rating with the AMSTAR 2 assessment tool found that overall confidence in their results was critically low. Conclusion This study found that the quality of recent meta-analyses on the utility of the staging of endometrial cancer with sentinel node biopsy, evaluated by the AMSTAR 2 assessment tool, is classified as critically low, and, therefore, these meta-analyses are not reliable in the summary of their studies.

Malignant Uterine Neoplasms Attended at a Brazilian Regional Hospital: 16-years Profile and Time Elapsed for Diagnosis and Treatment

Abstract Objective The present study aims to evaluate the profile of endometrial carcinomas and uterine sarcomas attended in a Brazilian cancer center in the period from 2001 to 2016 and to analyze the impact of time elapsed from symptoms to diagnoses or treatment in cancer stage and survival. Methods This observational study with 1,190 cases evaluated the year of diagnosis, age-group, cancer stage and histological type. A subgroup of 185 women with endometrioid histology attended in the period from 2012 to 2017 was selected to assess information about initial symptoms, diagnostic methods, overall survival, and to evaluate the influence of the time elapsed from symptoms to diagnosis and treatment on staging and survival. The statistics used were descriptive, trend test, and the Kaplan-Meier method, with p-values < 0.05 for significance. Results A total of 1,068 (89.7%) carcinomas (77.2% endometrioid and 22.8% non-endometrioid) and 122 (10.3%) sarcomas were analyzed, with an increasing trend in the period (p < 0.05). Histologies of non-endometrioid carcinomas, G3 endometrioid, and carcinosarcomas constituted 30% of the cases. Non-endometrioid carcinomas and sarcomas were more frequently diagnosed in patients over 70 years of age and those on stage IV (p < 0.05). The endometrioid subgroup with 185 women reported 92% of abnormal uterine bleeding and 43% diagnosis after curettage. The average time elapsed between symptoms to diagnosis was 244 days, and between symptoms to treatment was 376 days, all without association with staging (p = 0.976) and survival (p = 0.160). Only 12% of the patients started treatment up to 60 days after diagnosis. Conclusion The number of uterine carcinoma and sarcoma cases increased over the period of 2001 to 2016. Aggressive histology comprised 30% of the patients and, for endometrioid carcinomas, the time elapsed between symptoms and diagnosis or treatment was long, although without association with staging or survival.

Assessment of risk factors associated with post-molar gestational trophoblastic neoplasia: a retrospective cohort

Evaluate the risk factors for the development of post-molar gestational trophoblastic neoplasia. Retrospective cohort study with 320 women with gestational trophoblastic disease (GTD) followed in a tertiary hospital from January 2005 to January 2020. Data referring to the women's sociodemographic profile, clinical, laboratory and treatment aspects and types of GTD were analyzed. The mean age of women with the benign form was 26.4±8.6 years and with the malignant forms 26.9±8.5 years (p=0.536). Most women with malignant forms came from regions further away from reference center (p=0.012), had vesicle elimination at the time of diagnosis (p=0.028) and needed more than one uterine evacuation (p<0.001) when compared to the benign forms. There was no difference between laboratory tests in both forms. Being between 30 and 39 years old increased the chance of developing invasive mole by 2.5 (p=0.004; 95%CI:1.3-4.9) and coming from regions far from reference center by 4.01 (p=0.020; CI95%: 1.2-12.9). The women with the highest risk of malignant forms were those with the longest time of become normal on human gonadotrophic hormone (hCG) testing (each week the risk increases 1.3 times; p<0.001, 95%CI: 1.2-1.3). The prolonged hCG fall curve is the main indicator of an increased chance of GTN. Women from regions further away from reference center have a greater chance of developing malignant forms, probably due to the difficulty in accessing the reference center and, therefore, adequate follow-up that would allow early identification of more serious cases.

Advances in artificial intelligence for the early detection of cervical cancer in adult women: a scoping review

To synthesize current scientific evidence on the benefits and potential contributions of integrating AI-based technologies with traditional diagnostic methods used for the detection and early diagnosis of cervical cancer in adult women. An exhaustive search was conducted in academic databases (PubMed, Scopus and BIREME) using specific search terms and Boolean operators in December 2024. Independently conducted by three researchers across all databases, the selection process included articles involving adult women with either suspected or confirmed cervical cancer, in which the application of artificial intelligence (AI) technologies was examined across various techniques used for early diagnosis of the disease, such as cytology, colposcopy, and radiological imaging, among others. Only articles published between 1999 and 2022 were included. The included articles were reviewed in full text by all authors, and relevant data were extracted and organized into a chart comprising the following items: author and year of publication, title, study design, type of AI technology used, and a summary of the content. AI, particularly through Machine Learning (ML) algorithms, demonstrated significant improvements in the accuracy, sensitivity, and efficiency of cervical lesion classification when combined with conventional diagnostic techniques like cervical cytology, colposcopy, and biopsy. This combined approach outperformed traditional methods used in isolation. The integration of AI with standard cervical cancer screening and diagnostic methods offers substantial benefits, including faster detection times, reduced workload for pathologists, and improved patient outcomes by facilitating earlier treatment initiation and reducing diagnostic variability. Considering the available literature, the use of AI may offer potential benefits; however, further studies are required.

The occurrence of cervical high-grade lesions in women outside the recommended age screening

This study aimed to assess the prevalence of cervical High-Grade Squamous Intraepithelial Lesions (HSIL) in women outside the screening age recommended by the Brazilian Guidelines for Cervical Cancer Screening (under 25 and over 64 years old). The cross-sectional study was conducted at a reference hospital in Rio de Janeiro with a histopathological report of CIN 2 + from January 2010 to December 2020 through the analysis of medical records. Among 406 women diagnosed with Cervical Intraepithelial Neoplasia (CIN) 2+, 63 patients (15.5%) were outside the recommended screening age, 17(4.2%) of whom were under the age of 25, and 46 (11.3%) were older than 64 years. CIN 2 was most prevalent in women under 25 years old (29.4%); CIN 3 in those between 25 and 64 years old (55.1%); and invasive cancer predominated in women over 64 years old, with statistical significance (<0.001). The higher frequency of CIN 2 in young women under 25 years old supports the transient nature of these lesions, reinforcing that screening this age group may lead to unnecessary treatment. Conversely, the detection of high-grade lesions and cancer in older women is a consequence of inadequate screening earlier in life.

The top hat procedure does not impact the management of women treated by LEEP in cervical cancer screening

To describe Top-hat results and their association with margin status and disease relapse in a referral facility in Brazil. A retrospective study of 440 women submitted to LEEP to treat HSIL, in which 80 cases were complemented immediately by the top hat procedure (Top-hat Group - TH). TH Group was compared to women not submitted to Top-hat (NTH). The sample by convenience included all women that underwent LEEP from January 2017 to July 2020. The main outcome was the histological result. Other variables were margins, age, transformation zone (TZ), depth, and relapse. The analysis used the Chi-square test and logistic regression. The TH Group was predominantly 40 and older (NTH 23.1% vs. TH 65.0%, p<0.001). No difference was found in having CIN2/CIN3 as the final diagnosis (NTH 17.0% vs. TH 21.3%, p=0.362), or in the prevalence of relapse (NTH 12.0% vs. TH 9.0%, p=0.482). Of the 80 patients submitted to top hat, the histological result was CIN2/CIN3 in eight. A negative top hat result was related to a negative endocervical margin of 83.3%. A CIN2/CIN3 Top-hat result was related to CIN2/CIN3 margin in 62.5% (p=0.009). The chance of obtaining a top hat negative result was 22.4 times higher (2.4-211.0) when the endocervical margin was negative and 14.5 times higher (1.5-140.7) when the ectocervical margin was negative. The top hat procedure did not alter the final diagnosis of LEEP. No impact on relapse was observed. The procedure should be avoided in women of reproductive age.

Human papillomavirus-based vs. cytology for cervical cancer screening: a systematic review with meta-analysis

To evaluate the performance of HPV-based testing compared to cytology in primary cervical cancer screening. This meta-analysis included randomized trials comparing HPV-based screening with cytology in women aged 20-69 with at least one year of follow-up. Studies with overlapping populations, combining screening methods, lacking outcomes of interest, or study protocols were excluded. CENTRAL, PubMed/MEDLINE, and Embase were searched on April 12, 2025. The main outcome is the detection rate of cervical neoplasia grade 2 or worse (CIN2+). Analyses followed Cochrane and PRISMA guidelines. A total of 1,707 articles were identified. After removing duplicate records and excluding studies according to the pre-established criteria, 24 were selected for full-text review. Finally, eight were included in the statistical analysis, totaling 414,846 patients in a per-protocol assessment. The detection rate of CIN2+ by HPV-based tests was 61% higher compared to conventional or liquid-based cytology [RR 1.61; 95% CI 1.30, 1.98; p < 0.00001]. While our findings demonstrate the superior sensitivity of HPV testing, there are concerns about potential overdiagnosis and overtreatment. The absence of defined management protocols for HPV-positive patients contributes to this challenge. Therefore, risk-stratification strategies, such as HPV DNA genotyping, are essential to optimize clinical care and reduce these risks. HPV-based screening has a greater capacity to identify cervical neoplasia than cytology.PROSPERO registry: ID CRD420251027259.

Germline Mutations Landscape in a Cohort of the State of Minas Gerais, Brazil, in Patients Who Underwent Genetic Counseling for Gynecological and Breast Cancer

Abstract Objective The present study evaluated the profile of germline mutations present in patients who underwent genetic counseling for risk assessment for breast cancer (BC), ovarian cancer (OC), and endometrial cancer (EC) with a possible hereditary pattern. Methods Medical records of 382 patients who underwent genetic counseling after signing an informed consent form were analyzed. A total of 55.76% of patients (213/382) were symptomatic (personal history of cancer), and 44.24% (169/382) were asymptomatic (absence of the disease). The variables analyzed were age, sex, place of birth, personal or family history of BC, OC, EC, as well as other types of cancer associated with hereditary syndromes. The Human Genome Variation Society (HGVS) nomenclature guidelines were used to name the variants, and their biological significance was determined by comparing 11 databases. Results We identified 53 distinct mutations: 29 pathogenic variants, 13 variants of undetermined significance (VUS), and 11 benign. The most frequent mutations were BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G &gt; T, and BRCA2 c.2T&gt; G. Furthermore, 21 variants appear to have been described for the first time in Brazil. In addition to BRCA1/2 mutations, variants in other genes related to hereditary syndromes that predispose to gynecological cancers were found. Conclusion This study allowed a deeper understanding of the main mutations identified in families in the state of Minas Gerais and demonstrates the need to assess the family history of non-gynecological cancer for risk assessment of BC, OC, and EC. Moreover, it is an effort that contributes to population studies to evaluate the cancer risk mutation profile in Brazil.

Combined Oral Contraceptive Use and the Risk of Cervical Cancer: Literature Review

AbstractCervical cancer (CC) is caused by persistent infection of human papillomavirus of high oncogenic risk (hr-HPV); however, several cofactors are important in its carcinogenesis, such as smoking, multiparity, and prolonged use of oral hormonal contraceptives (COCs). Worldwide, 16% of women use COCs, whereas in Brazil this rate is of ∼ 30%. The safety and adverse effects of COCs are widely discussed in the literature, including the increase in carcinogenic risk. Due to the existence of several drugs, combinations, and dosages of COCs, it is hard to have uniform information in epidemiological studies. Our objective was to perform a narrative review on the role of COCs use in the carcinogenesis of cervical cancer. Several populational studies have suggested an increase in the incidence of cervical cancer for those who have used COCs for &gt; 5 years, but other available studies reach controversial and contradictory results regarding the action of COCs in the development of CC.

Underestimated Cervical Cancer among Women over 65 Years Old: Is It Time to Revise the Screening Target Age Group?

Abstract Objective To compare cytological and histological results from women &gt; 64 years old who followed the Brazilian national cervical cancer screening guidelines with those who did not. Methods The present observational retrospective study analyzed 207 abnormal cervical smear results from women &gt; 64 years old in a mid-sized city in Brazil over 14 years. All results were reported according to the Bethesda System. The women were divided into those who followed the screening guidelines and those who did not. Results Atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion cytology results were found in 128 (62.2%) cases. Of these, 112 (87.5%) had repeated cytology with positive results. The other 79 (38.1%) with abnormal results should have been referred to colposcopy and biopsy. Out of 41 (51.9%) biopsied women, 23 (29.1%) had a confirmed diagnosis of neoplasia or precursor lesion. In contrast, among the 78 (37.7%) biopsied patients, 40 (51.3%) followed the guideline recommendations, with 9 (22.5%) positive biopsies. Of the 38 (48.7%) women who did not follow the guidelines, there were 24 (63.1%) positive results. Women who did not follow the guidelines demonstrated higher chances of cancer and precursor lesions (odds ratio [OR]: 5.904; 95% confidence interval [CI]: 2.188–15.932; p = 0.0002). Conclusion Women &gt; 64 years old who did not follow the national screening protocol showed significant differences in the frequency of abnormal results and severity of diagnosis compared with those who followed the protocol.

The importance of the quadrivalent HPV vaccine in the elimination of cervical cancer in Brazil

Conservative Treatment of Stage IA1 Cervical Carcinoma Without Lymphovascular Space Invasion: A 20-year Retrospective Study in Brazil

Abstract Purpose: To evaluate recurrence rates and risk factors among women with stage IA1 cervical cancer without lymph vascular space invasion managed conservatively. Methods: retrospective review of women with stage IA1 squamous cervical cancer who underwent cold knife cone or loop electrosurgical excision procedure, between 1994 and 2015, at a gynecologic oncology center in Southern Brazil. Age at diagnosis, pre-conization findings, conization method, margin status, residual disease, recurrence and survival rates were collected and analyzed. Results: 26 women diagnosed with stage IA1 squamous cervical cancer without lymphovascular space invasion underwent conservative management and had at least 12 months follow-up. The mean follow-up was 44.6 months. The mean age at diagnosis was 40.9 years. Median first intercourse occurred at age 16 years, 11.5% were nulliparous and 30.8% were current or past tobacco smokers. There was one Human immunodeficiency virus positive patient diagnosed with cervical intraepithelial neoplasia grade 2 at 30 months after surgery. However, there were no patients diagnosed with recurrent invasive cervical cancer and there were no deaths due to cervical cancer or other causes in the cohort. Conclusion: Excellent outcomes were noted in women with stage IA1 cervical cancer without lymphovascular space invasion and with negative margins who were managed conservatively, even in a developing country.

When is There no Benefit in Performing a Biopsy in the Suspicion of Intraepithelial Lesions of the Cervix?

Abstract Objective To evaluate whether colposcopy-directed biopsy is necessary to increase the accuracy of diagnosing cervical intraepithelial lesions in relation to colposcopy. Methods We performed a retrospective, observational study by analyzing medical records obtained from Hospital de Clínicas do Paraná from February 2008 to February 2018. Patients with results of Pap tests, colposcopy, colposcopy-directed biopsy, and surgical procedures (high-frequency surgery or cold conization) were included. Data such as quadrants involved during colposcopy and age differences were also analyzed. Results A total of 299 women were included. Colposcopy was found to have an accuracy rate of 76.25% (95% confidence interval [CI], 71.4–81.1). Among the highest-grade lesions, the accuracy rate was 80.5% (95% CI, 75.7–85.3). The accuracy rates for biopsy were 79.6% (95% CI, 75–84.2) and 84.6% (95% CI, 80–89.1) for the highest-grade lesions. High-grade lesions were accurately confirmed in 76.9% and 85% of patients with 1 and 2 or more affected quadrants, respectively. For women younger than 40 years, the accuracy rates were 77.6% and 80.8% for colposcopy and biopsy, respectively. For women 40 years or older, the accuracy rates were 72.5% and 76.3% for colposcopy and biopsy, respectively. Conclusion There is no difference between the accuracy of colposcopy and that of biopsy in diagnosing cervical intraepithelial lesions in relation with the result of conization. The patients who received the greatest benefit when biopsy was not performed were those with high-grade lesions at colposcopy, a lesion involving 2 or more quadrants, and those younger than 40 years.

Risk Profile of High-grade Cervical Lesions and Cervical Cancer Considering the Combination of Cytology, HPV Genotype, and Age among Women Undergoing Colposcopy

Abstract Objective The present study aims to establish a risk profile for high-grade cervical lesions and cervical cancer (CIN2 + ) in women undergoing colposcopy at the Hospital do Câncer de Barretos, through the analysis of Human Papillomavirus (HPV) infection, cervical cytology, and patient's age. Methods Retrospective cross-sectional study based on a computerized database of women aged ≥ 18 years old who underwent colposcopy at the Prevention Department of the Hospital do Câncer de Barretos from 2017 to 2019. Results A total of 3,411 women were included, 58.0% were positive for high-risk-HPV test, with a higher prevalence of CIN2+ for HPV16 (30.3%) and other HPV (45.0%). Cytological findings that suggest invasive cervical cancer (squamous cells or adenocarcinoma), regardless of the status of HPV test, showed 100% diagnosis of CIN2 + , while atypias that suggest high-grade lesions, HSIL and ASC-H, positive for HPV test, showed in 86 and 55.2%, respectively, diagnosis of CIN2 + . ASC-H cytological results among women aged &gt; 40 years old and negative HPV were mainly associated with benign findings. We observed that ≤ CIN1 has a higher prevalence among older women with negative HPV, while for high-grade lesions there is an increase among young women HPV16- and/or 18-positive. In cancer diagnosis, we observed a predominance of HPV 16/18 regardless of the age group. Conclusion The highest risks of precursor lesions and cervical cancer were found among women with positive HPV 16/18 tests and severe cytological atypia in population screening tests. In addition, cytological findings of ASC-H HPV negative in women &gt; 40 years old usually represent benign findings in histological investigation.

Human Papillomavirus 16 Lineage D is Associated with High Risk of Cervical Cancer in the Brazilian Northeast Region

Abstract Objective Similar to Human Papillomavirus (HPV) genotypes, different lineages of a genotype also have different carcinogenic capabilities. Studies have shown that specific genotype lineages of oncogenic HPV are associated with variable risks for the development of cervical intraepithelial neoplasia (CIN2/CIN3) and cervical cancer. The present study aimed to analyze the genetic diversity of the HPV16 genotype in women with CIN2/CIN3 and cervical cancer, from the northeast region of Brazil. Methods A cross-sectional multicenter study was conducted in the northeast region of Brazil, from 2014 to 2016. This study included 196 cases of HPV16 variants (59 and 137 cases of CIN2/CIN3 and cervical cancer, respectively). The difference of proportion test was used to compare patients with CIN2/CIN3 and cervical cancer, based on the prevalent HPV16 lineage (p &lt; 0.05). Results According to the histopathological diagnosis, the percentage of lineage frequencies revealed a marginal difference in the prevalence of lineage A in CIN2/CIN3, compared with that in cervical cancer (p = 0.053). For lineage D, the proportion was higher in cancer cases (32.8%), than in CIN2/CIN3 cases (16.9%), with p = 0.023. Conclusion HPV16 lineage A was the most frequent lineage in both CIN2/CIN3 and cervical cancer samples, while lineage D was predominant in cervical cancer, suggesting a possible association between HPV16 lineage D and cervical cancer.

Preoperative Differentiation of Benign and Malignant Non-epithelial Ovarian Tumors: Clinical Features and Tumor Markers

Abstract Objective To evaluate the role of clinical features and preoperative measurement of cancer antigen 125 (CA125), human epididymis protein (HE4), and carcinoembryonic antigen (CEA) serum levels in women with benign and malignant non-epithelial ovarian tumors. Methods One hundred and nineteen consecutive women with germ cell, sex cord-stromal, and ovarian leiomyomas were included in this study. The preoperative levels of biomarkers were measured, and then surgery and histopathological analysis were performed. Information about the treatment and disease recurrence were obtained from the medical files of patients. Results Our sample included 71 women with germ cell tumors (64 benign and 7 malignant), 46 with sex cord-stromal tumors (32 benign and 14 malignant), and 2 with ovarian leiomyomas. Among benign germ cell tumors, 63 were mature teratomas, and, among malignant, four were immature teratomas. The most common tumors in the sex cord-stromal group were fibromas (benign) and granulosa cell tumor (malignant). The biomarker serum levels were not different among benign and malignant non-epithelial ovarian tumors. Fertility-sparing surgeries were performed in 5 (71.4%) women with malignant germ cell tumor. Eleven (78.6%) patients with malignant sex cord-stromal tumors were treated with fertility-sparing surgeries. Five women (71.4%) with germ cell tumors and only 1 (7.1%) with sex cord-stromal tumor were treated with chemotherapy. One woman with germ cell tumor recurred and died of the disease and one woman with sex cord-stromal tumor recurred. Conclusion Non-epithelial ovarian tumors were benign in the majority of cases, and the malignant cases were diagnosed at initial stages with good prognosis. The measurements of CA125, HE4, and CEA serum levels were not useful in the preoperative diagnosis of these tumors.

Adnexal mass: diagnosis and management

Diagnostic Value of the Neutrophil/Lymphocyte Ratio, Platelet/Lymphocyte Ratio, and Thrombocytosis in the Preoperative Investigation of Ovarian Masses

Abstract Objective To evaluate the diagnostic accuracy of cancer antigen 125 (CA125) and complete blood count (CBC) parameters, such as the neutrophil to lymphocyte ratio (NLR), the platelet to lymphocyte ratio (PLR), and thrombocytosis in patients with ovarian masses. Methods The present is a retrospective study conducted at a single tertiary hospital from January 2010 to November 2016. We included consecutive women referred due to suspicious adnexal masses. The CBC and CA125 were measured in the serum of 528 women with ovarian masses before surgery or biopsy. We evaluated the diagnostic performance of the NLR, PLR, platelets (PLTs), CA125, and the associations between them. We tested the clinical utility of the CBC parameters and CA125 in the discrimination of ovarian masses through decision curve analysis (DCA). Results The best balance between sensitivity and specificity was obtained by the associations of CA125 or PLTs ≥ 350/nL, with 70.14% and 71.66%, CA125 or PLTs ≥ 400/nL, with 67.30% and 81.79%, CA125 or PLR, with 76.3% and 64.87%, and CA125 or NLR, with 71.09% and 73.89% respectively. In the DCA, no isolated CBC parameter presented a higher clinical utility than CA125 alone. Conclusion We showed that no CBC parameter was superior to CA125 in the prediction of the malignancy of ovarian tumors in the preoperative scenario.

Practical Recommendations for the Management of Benign Adnexal Masses

Abstract Objective To perform a comprehensive review to provide practical recommendations regarding the diagnosis and treatment of benign adnexal masses, as well as information for appropriate consent, regarding possible loss of the ovarian reserve. Methods A comprehensive review of the literature was performed to identify the most relevant data about this subject. Results In total, 48 studies addressed the necessary aspects of the review, and we described their epidemiology, diagnoses, treatment options with detailed techniques, and perspectives regarding future fertility. Conclusions Adnexal masses are extremely common. The application of diagnosis algorithms is mandatory to exclude malignancy. A great number of cases can be managed with surveillance. Surgery, when necessary, should be performed with adequate techniques. However, even in the hands of experienced surgeons, there is a significant decrease in ovarian reserves, especially in cases of endometriomas. There is an evident necessity of studies that focus on the long-term impact on fertility.

Association of insulin-like growth factor II mrna-binding protein 3 (IMP3) expression with prognostic and morphological factors in endometrial cancer

Endometrial cancer (EC) is a heterogeneous disease with recurrence rates ranging from 15 to 20%. The discrimination of cases with a worse prognosis aims, in part, to reduce the length of surgical staging in cases with a better prognosis. This study aimed to evaluate the association between Insulin-like growth factor II mRNA-binding protein 3 (IMP3) expression and prognostic and morphological factors in EC. This retrospective, cross-sectional, analytical study included 79 EC patients - 70 endometrioid carcinoma (EEC) and 9 serous carcinoma (SC) - and 74 benign endometrium controls. IMP3 expression was evaluated by immunohistochemistry-based TMA (Tissue Microarray), and the results were associated with morphological and prognostic factors, including claudins 3 and 4, estrogen and progesterone receptors, TP53, and KI67. IMP3 expression was significantly higher in SC compared to EEC in both extent (p<0.001) and intensity (p=0.044). It was also significantly associated with worse prognostic factors, including degree of differentiation (p=0.024, p<0.001), staging (p<0.001; p<0.001) and metastasis (p=0.002; p<0.001). IMP3 expression was also significant in extent (p=0.002) in endometrial tumors compared with controls. In addition, protein TP53 and KI67 showed significant associations in extent and intensity, respectively. IMP3 expression was associated with worse prognostic factors studied. These findings suggest that IMP3 may be a potential biomarker for EC poorer prognosis.

Evaluation of chronic radiation proctitis in patients with cervical cancer treated with pelvic radiotherapy: a cross-sectional study

A combination of chemotherapy and pelvic radiotherapy is recommended to treat locally advanced cervical cancer (CC), which has been associated with acute and chronic toxicities, especially radiation proctitis (RP). The objective of this study was to evaluate the frequency of RP and treatment management in females with CC who underwent pelvic radiotherapy at an oncology referral hospital. This cross-sectional study analyzed the medical records of patients treated with radiotherapy for CC between 2015-2017. We assessed sociodemographic, lifestyle, cancer, treatment, and clinical variables. We identified 298 records of females with CC who underwent pelvic radiotherapy during the defined period. Of these, 14 records were duplicates, 25 were excluded for lacking essential information, and 33 were missing in the archive. Accordingly, 226 relevant medical records were analyzed, with data regarding sociodemographic, clinical, cancer-related, treatment-related, and RP-related variables collected. Pearson's chi-square test was used to compare symptomatic and non-symptomatic patients. Fisher's exact test was used to compare chemotherapy doses. Statistical analysis was performed with Stata V12.1. A P-value less than 0.05 was considered significant. The median patient age was 48 years (interquartile range 38-61). Patients predominantly had CC stages IIB and IIIB (>70%). Of the 226 females analyzed, 87(38.5%) experienced RP symptoms, represented by rectal bleeding; of these, 59 underwent colonoscopy, confirming RP in 58(98.3%). Accordingly, of the 226 females analyzed, 58(25.7%) had a confirmed diagnosis of RP. There was a statistically significant association between rectal bleeding and cumulative radiation dose (P < 0.001) and the presence of systemic arterial hypertension (P = 0.036). Regarding treatment, 38(65.5%) participants underwent argon plasma coagulation (APC), and of these, 22(57.9%) had no post-treatment macroscopic bleeding. Patients with CC who received radiotherapy at an oncology referral service had a high frequency of RP, and APC helped control bleeding in certain patients.

A novel marker in the ovarian preservation approach to endometrial cancer: systemic immune inflammatory index

This study aims to to evaluate the frequency of ovarian involvement in endometrial cancer patients aged 50 years and younger, identify associated clinicopathological factors, and uniquely assess the role of the Systemic Immune-Inflammatory Index (SII) in predicting ovarian involvement. Patients aged 50 years and younger diagnosed with endometrial cancer between 1992 and 2022 were retrospectively analyzed. Two groups were formed based on adnexal involvement: those with (ovarian metastasis or synchronous ovarian cancer) and without adnexal involvement. Clinicopathological predictors of adnexal involvement were evaluated. Preoperative complete blood count values (platelet, leukocyte, lymphocyte, and neutrophil counts) were used to calculate inflammatory indices: PLR (platelet-to-lymphocyte ratio), NLR (neutrophil-to-lymphocyte ratio), and SII (neutrophil × platelet / lymphocyte). A two-group analysis was performed based on the cut-off values of statistically significant parameters. Univariate and multivariate logistic regression analyses were conducted. Among 205 patients, histopathological ovarian metastasis was identified in 5.9% (n=12), and synchronous ovarian tumors in 2.4% (n=5). Significant differences were observed in neutrophil counts, NLR, and SII values between the groups (p<0.05). ROC analysis showed the optimal SII cut-off value as 992.58, with 70% sensitivity and 76% specificity (AUC=0.726). Ovarian involvement was significantly more frequent in patients with SII ≥ 992 (p<0.05). Univariate analysis revealed that myometrial invasion, LVSI, cervical stromal invasion, lymph node metastasis, omental involvement, grade of tumor, NLR and SII were significantly associated with ovarian involvement (p<0.05). Multivariate analysis identified histological grade, myometrial invasion, pelvic lymph node metastasis and SII as independent risk factors (p<0.05). Ovarian involvement is uncommon in patients under 50 years of age with low-grade tumors, absence of myometrial invasion, negative pelvic lymph nodes, and preoperative SII < 992.58. Ovarian-sparing surgery may be a safe option in selected cases, and SII could serve as a valuable index in guiding ovarian preservation decisions.

Gastrin-releasing peptide receptor: a promising new biomarker to identify cervical precursor lesions and cancer

This study aimed to verify the relation between gastrin-releasing peptide receptor (GRPR), oncogenic Human Papillomavirus (HPV) and cervical lesions severity. GRPR mRNA levels were evaluated in cervical cancer-derived cell lines and in primary keratinocytes expressing HPV16 oncogenes by RT-PCR. GRPR protein expression was assessed by immunohistochemistry in organotypic cell cultures derived from keratinocytes transduced with HPV16 oncogenes and in 208 cervical samples, including 59 non-neoplastic tissue, 28 cervical intraepithelial neoplasia grade 3 (CIN3), 44 squamous cell carcinomas (SCC) and 77 adenocarcinomas (ADC). Generic primers (GP5+/GP6+) were used to identify HPV infection in tissue samples. Experiments involving cell lines were analyzed through non-parametric tests (Kruskal Wallis), and Fisher's Exact Test for human tissues samples. All statistical tests were considered significant at p <0.05. Immunohistochemical evaluation was conducted independently and blindly by two observers (AD- LO). Any discordant findings were resolved through discussion to reach a consensus score. GRPR mRNA levels were not increased in cells expressing HPV16 or HPV18 oncogenes. However, at the protein level, GRPR was upregulated in organotypic cell cultures containing HPV oncogenes. Besides, it was identified an association between GRPR expression and cervical lesion severity (p < 0.0001). The detection rate of high-risk HPV DNA was directly correlated with cervical disease. Nonetheless, HPV infection was not directly associated with GRPR in cervical samples. GRPR expression is highly predictive of cervical lesion severity, irrespective of HPV infection and might contribute to improving patient's therapeutic management as well as being used a marker of disease progression.

Analysis of vaginal microbiota before and after treatment of high-grade squamous intraepithelial lesions of the uterine cervix

HPV infection is considered the most common sexually transmitted virus today. The persistence of HPV is the main cause for the development of precursor lesions and cervical cancer. There are environmental and non-environmental factors that contribute to the persistence of the virus. Studies indicate a possible relationship between the vaginal microbiota (environmental factor) and the risk of high-grade cervical squamous intraepithelial lesions and cervical cancer. This study evaluates the association between the type of vaginal microbiota and the occurrence of high-grade squamous intraepithelial lesions of the cervix. Observational, longitudinal, prospective, and analytical studies carried out between 2019 and 2021, which evaluated the vaginal microbiota of patients diagnosed with high-grade cervical squamous intraepithelial lesion before and after treatment in two collections with an interval of 6 months, using scrapings and vaginal swabs. In Group I (with lesions) 28 women participated and 29 in Group II (without lesions). According to Nugent, in the initial collection of Group I, 16 women (57%) had lactobacillary microbiota, eight (28%) intermediate, and four (14%) coccus. In Group II, twenty-one (75%) were lactobacillary, one (3%) was intermediate, and seven (24%) werecoccus. With p=0.03. According to Nugent's criteria, there was an association between the type of vaginal microbiota and the occurrence of high-grade cervical squamous intraepithelial lesions of the cervix. The same was not observed in the Donders classification. Studies with a larger sample are needed to confirm our results.

Clinical, histopathological and immunohistochemical analysis of vulvar squamous cell carcinoma

The average age of patients with vulvar squamous cell carcinoma (SCC) has been reported to have declined. Human papilloma virus (HPV)-related lesions have been shown to be associated with the expression of the immunohistochemical (IHC) marker p16. Non-HPV-related tumors have been characterized by p53 abnormal expression and PDL1 expression. We aimed to evaluate the correlation between these markers and vulvar SCC and to relate it to the clinical and pathological characteristics. Histopathologic assessments and IHC analyses of p16, p53, and PDL1 were performed in 41 samples of vulvar SCC collected between 2016 and 2021. The data were correlated with clinical and pathological characteristics of the patients. The mean age of the patients was 72.1 years. Positive p16 and PDL1 staining was detected in 24.4% and 17.1% of the samples, respectively. p53 expression was negative in 19.5% of the samples, whereas it was overexpressed in 24.4%. p16-positive tumors showed a smaller depth of invasion (DOI) (p = 0.014), while tumors with p53 abnormal expression showed greater DOI (p = 0.041). PDL1 expression was correlated with increased number of inflammatory cells (p = 0.055). In addition, lesions with lymphovascular space invasion were p16-negative. In our sample, regarding to the SCC incidence the patients' mean age did not change. The expression of p16 was inversely correlated with p53 results. Tumors with p53 abnormal expression and absence of p16 showed a greater DOI. Our data suggest an association between PDL1 expression and increased inflammatory infiltrates in vulvar SCC.

The role of HIV as an independent risk factor to cervical HSIL recurrence

To evaluate the role of being human immunodeficiency virus (HIV) positive for predicting the risk of recurrence in women with a cervical high grade squamous intraepithelial lesion (HSIL) diagnosis. Retrospective observational case-control study, comprising HIV positive (case) and HIV negative (control) women in a 1:4 ratio. Women assisted by the Erasto Gaertner Hospital, between 2009-2018, with cervical HSIL diagnosis, submitted to treatment by Loop electrosurgical excision procedure (LEEP), and with a minimum follow-up of 18 months, were included. The immunological status, number and time to recurrence were analyzed, with p<0.05 considered significant. In a second analysis, only patients with free margins were evaluated. The sample consisted of 320 women (64 cases and 256 controls). Presence of HIV, CD4 levels <200 and detectable viral load (CV) were associated with high risk of recurrence, with odds ratio (OR) of 5.4 (p<0.001/95CI:2.8-10); 3.6 (p<0.001 /IC95:0.6-21.1) and 1.8 (p=0.039 /IC95:0.3-9.3), respectively. In the sample with free margins (n=271), this risk was also higher among seropositive patients, with OR 4.18 (p=0.001/95CI:1.8-9.2). HIV is an independent risk factor for cervical HSIL recurrence and reduced disease-free survival time. Glandular involvement, compromised margins, undetectable CV and CD4<200 also increase the risk of relapse.

The path to elimination: FEBRASGO 2023's targeted strategies against cervical cancer in Brazil

Systemic Inflammatory Patterns in Ovarian Cancer Patients: Analysis of Cytokines, Chemokines, and Microparticles

Abstract Objective To compare the patterns of systemic inflammatory response in women with epithelial ovarian cancer (EOC) or no evidence of malignant disease, as well as to evaluate the profile of systemic inflammatory responses in type-1 and type-2 tumors. This is a non-invasive and indirect way to assess both tumor activity and the role of the inflammatory pattern during pro- and antitumor responses. Materials and Methods We performed a prospective evaluation of 56 patients: 30 women without evidence of malignant disease and 26 women with EOC. The plasma quantification of cytokines, chemokines, and microparticles (MPs) was performed using flow cytometry. Results Plasma levels of proinflammatory cytokines interleukin-12 (IL12), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) interleukin-1 beta (IL-1β), and interleukin-10 (IL-10), and C-X-C motif chemokine ligand 9 (CXCL-9) and C-X-C motif chemokine ligand 10 (CXCL-10) were significantly higher in patients with EOC than in those in the control group. Plasma levels of cytokine interleukin-17A (IL-17A) and MPs derived from endothelial cells were lower in patients with EOC than in the control group. The frequency of leukocytes and MPs derived from endothelial cells was higher in type-2 tumors than in those without malignancy. We observed an expressive number of inflammatory/regulatory cytokines and chemokines in the cases of EOC, as well as negative and positive correlations involving them, which leads to a higher complexity of these networks. Conclusion The present study showed that, through the development of networks consisting of cytokines, chemokines, and MPs, there is a greater systemic inflammatory response in patients with EOC and a more complex correlation of these biomarkers in type-2 tumors.

High-risk Human Papillomavirus Testing for Triage of Women with Previous Cytological Abnormalities from the Vale do Ribeira Region

Abstract Objective To evaluate the performance of the hybrid capture 2 (HC2) high-risk papillomavirus (hrHPV) assay and cytological test in women with previous abnormalities, to detect cervical intraepithelial neoplasia grade 2 or worse (≥ CIN 2). Methods A cytological test and HC2 (Qiagen, Gaithersburg, Maryland, EUA) for hrHPV were conducted in 359 liquid-based (Sure Path, Becton Dickinson, TriPath Imaging, Burlington, NC, USA) samples collected from women from the Vale do Ribeira Region, during July 2013 and September 2015 with previous cytology classified as atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions (ASC-H), and atypical glandular cells (AGC). The histopathological examination was conducted in 179 women. The performance evaluations were calculated using the “exact” Clopper-Pearson 95% confidence interval (CI) test by MEDCALC (Medcalc Software Ltd, Ostend, Belgium). Results The ≥ CIN 2 frequency was 11.7% (21/179). The HC2 for hrHPV and repeat cytology to detect ≥ CIN 2 obtained, respectively, a sensitivity of 90.5% (95%CI = 69.6–98.8) and 90.5%, (95%CI = 69.6–98.8), a specificity of 65.8% (95% CI = 57.9–73.2) and 43.7% (95%CI = 35.8–51.8), a positive predictive value of 26.0% (95% CI = 21.4–31.3) and 17.6%, (95%CI = 14.9–20.6), and a negative predictive value of 98.1% (95%CI = 93.3–99.5) and 97.2% (95% CI = 90.1–99.2). Conclusion Hybrid capture 2 for hrHPV improves the performance of the detection of ≥ CIN 2, without compromising sensitivity, and provides a greater safety margin to return to the triennial screening of women undergoing follow-up due to previous abnormalities, without underlying ≥ CIN 2.

Analysis of Conization Results in Patients undergoing Hysterectomy for Uterine Adenocarcinoma

Abstract Objective To observe if the histopathological result of a conization performed after cervical adenocarcinoma in situ diagnosis is compatible with the histopathological analysis of a subsequent hysterectomy. Methods The present descriptive and observational research consisted of the analysis of the medical records of 42 patients who were diagnosed with in situ adenocarcinoma postconization. The analysis consisted of whether there was compatibility between the histopathological reports of conization and hysterectomy and if there was an association between adenocarcinoma in situ and another neoplasia (squamous disease). Interpretation of any immunohistochemistry reports obtained was also performed. In addition, clinical and epidemiological data were also analyzed. Results A total of 42 conizations were performed, 33 (79%) were cold knife conizations and 9 (21%) were loop electrosurgical excision procedures (LEEPs). Of the patients analyzed, 5 (10%) chose not to undergo subsequent hysterectomy to preserve fertility or were &lt; 25 years old. Out of the 37 patients with adenocarcinoma in situ who underwent subsequent hysterectomy, 6 (16%) presented with residual disease. This finding proved incompatible with the finding of the conizations, which had ruled out invasive cancer. Conclusion The prevalence of adenocarcinoma in situ increased in the past years. There is still a large part of the medical literature that advocates the use of conservative treatment for this disease, even though it is common knowledge that it is a multifocal disease. However, the majority of studies advocate that hysterectomy should remain the preferred treatment for women who have already completed their reproductive purpose.

Influence of Gender and Undergraduate Course on the Knowledge about HPV and HPV Vaccine, and Vaccination Rate among Students of a Public University

Abstract Objective To evaluate the knowledge related to human papillomavirus (HPV) infection and the rate of HPV vaccination among undergraduate freshmen and senior students of medicine, pharmacy, speech therapy, nursing and physical education in a Brazilian university. Methods A questionnaire concerning sociodemographic aspects, sexual background, and knowledge about HPV and its vaccine was filled out by 492 students. Three months later, a second questionnaire, concerning the new rate of vaccination, was applied to 233 students. Results Among the 290 women who answered the first questionnaire, 47% of the freshmen and 13% of the seniors stated they were not sexually active, as well as 11% of the 202 freshman and senior male students. Although the knowledge about HPV was higher among women, they reported a lower use of condoms. More than 83% of the women and 66% of the men knew that HPV can cause cervical cancer, but less than 30% of the students knew that HPV can cause vulvar, anal, penile and oropharyngeal cancer. Less than half of the students knew that HPV causes genital, anal and oropharyngeal warts. Comparing the students, the seniors had more knowledge of the fact that HPV is sexually transmitted, and that HPV infection can be asymptomatic. The rate of vaccination was of 26% for women, and of 8% for men, and it increased to 52% and 27% respectively among the 233 students evaluated in the second questionnaire. Conclusion As almost half of freshman women declared being sexually inactive, the investment in public health information programs and easier access to the HPV vaccine seem to be a useful strategy for undergraduate students.

Description of Referrals for Colposcopy in a Hospital in Brazil

Abstract Objective To describe the referral for colposcopy in a Hospital in Brazil and the relative frequency of patients who benefited from it, considering the correct indications for the examination and its final diagnoses. Methods A retrospective study was performed in the colposcopy service database of the Hospital Universitário de Taubaté, Taubaté, state of São Paulo, Brazil. The frequency validated in the analysis of the medical records of women referred for clinical indication or cytological alteration, attended from March 2015 to March 2017. The population selected and analyzed included 256 results that were correlated to the cytological, clinical data and the result of the colposcopy. Results Of the women referred, 45% presented out of the age of screening according to the guidelines of cervical cancer screening, 8.6% being adolescents and young adults &lt; 25 years old, and 36.4% of the patients being ≥ 65 years old. A total of 50% of the patients had no indication of colposcopy, that is, normal cytologies, benign changes, ectopia, cervicitis, atypical squamous cells of indeterminate significance (ASC-US) and low-grade intraepithelial lesion (LSIL) without persistence and normal clinical appearance. A total of 39.84% who underwent colposcopy had high-grade lesion or cancer results, thus benefiting from the adequate referral. Conclusion Most (60.16%) of the patients referred to the colposcopy service did not benefit from the referral for results without changes, such as negative colposcopies, histologies with no cervical intraepithelial neoplasm (CIN) or only CIN 1, or were out of the age for screening. These findings therefore demonstrate a significant number of unnecessary and inadequate referrals.

Is Surgical Treatment an Option for Locally Advanced Cervical Cancer in the Presence of Central Residual Tumor after Chemoradiotherapy?

Abstract Objective To evaluate the outcomes of surgical treatment in patients with chemoradiotherapy (CRT)-resistant and locally advanced cervical cancer (LACC). Methods Patients with LACC who underwent surgery due to resistance to CRT between 2005 and 2015 were reviewed retrospectively. Disease-free survival (DFS) and overall survival (OS) related factors were analyzed. Results A total of 23 patients were included in the study and the median age was 51 years old. A total of 14 patients (60.8%) experienced recurrence; among these recurrences, 8 of them were local, 5 were distant, 1 was both distant and local. A total of 9 patients (39%) died. The Median DFS and OS durations were 15 and 32 months, respectively. A total of 17 patients (74%) had undergone simple hysterectomy, 4 (17%) radical hysterectomy, and 2 (9%) total pelvic exenteration. Postoperative grade 3 and 4 complications were seen in 12 patients (52%). Macroscopic tumor presence in the pathology specimen was associated with distant recurrence and positive surgical margins with local recurrence (Log-Rank test p = 0.029 and p = 0.048, respectively). The only factor associated with OS was surgical margin positivity (Log-Rank test p = 0.008). The type of surgery, grades 3 and 4 postoperative complications, brachytherapy, and tumor histology were not associated with recurrence. Conclusion In patients with LACC, hysterectomy is an option in the presence of a central residual tumor after CRT. However, the risk of grades 3 and 4 complications of performed surgery is high. The presence of macroscopic tumor in the pathology specimen and positive surgical margins are poor prognostic factors. The goal of the surgeon should be to achieve a negative surgical margin. It does not seem important if the surgery is simple or radical.

Cervical Mesonephric Adenocarcinoma: A Case Report of a Rare Gynecological Tumor from Embryological Remains of the Female Genital Tract

Abstract Introduction Malignant mesonephric tumors are uncommon in the female genital tract, and they are usually located where embryonic remnants of Wolffian ducts are detected, such as the uterine cervix. The information about these tumors, their treatment protocol, and prognosis are scarce. Case report A 60-year-old woman with postmenopausal vaginal bleeding was initially diagnosed with endometrial carcinoma. After suspicion co-testing, the patient underwent a loop electrosurgical excision of the cervix and was eventually diagnosed with mesonephric adenocarcinoma. She was subjected to a radical hysterectomy, which revealed International Federation of Gynecology and Obstetrics (FIGO) IB1 stage, and adjuvant radiotherapy. The follow-up showed no evidence of recurrence after 60 months. Conclusion We present the case of a woman with cervical mesonephric adenocarcinoma. When compared with the literature, this case had the longest clinical follow-up without evidence of recurrence, which reinforces the concept that these tumors are associated with a favorable prognosis if managed according to the guidelines defined for the treatment of patients with cervical adenocarcinomas. Though a rare entity, it should be kept in mind as a differential diagnosis for other cervical cancers.

HPV infection - Screening, diagnosis and management of HPV-induced lesions

Advanced Cervical Cancer: Leveraging the Historical Threshold of Overall Survival

HPV Vaccination and Screening with High-Performance Test: Brazilian Evidence

High-Grade Transformation in Adenoid Cystic Carcinoma of the Bartholin Gland: Case Report

Abstract Introduction In the present study, we report a case of primary adenoid cystic carcinoma (ACC) of the Bartholin gland with high-grade transformation (HGT). Adenoid cystic carcinoma of the Bartholin gland is a rare tumor and HGT has only been reported in head and neck tumors. Case Report A 77-year-old woman with a non-ulcerated vulvar lesion on the topography of the right Bartholin gland. The patient was submitted to tumor resection followed by V–Y island flap and adjuvant radiotherapy. The histopathological examination revealed primary ACC of the Bartholin gland, with areas of HGT and extensive perineural invasion. The immunohistochemical study with p53 showed a diffuse and strong positive reaction in areas with HGT. After 24 months of follow-up, the patient presented distant metastases and died, despite having undergone to chemotherapy. Conclusion As far as we know, this case is the first description in the literature of HGT in ACC of the Bartholin gland, and HGT appears to be associated with tumor aggressiveness.

Cellular Angiofibroma: A Rare Vulvar Tumor Case Report

AbstractCellular angiofibroma (CA)is a rare benign mesenchymal tumor. In women, it occurs mainly in the vulvovaginal region, with vulvar location in 70% of the cases. Its clinical presentation is nonspecific and similar to several other vulvar tumors of different cellular origins. Thus, its histological and immunohistochemical features allow distinction from other tumors. Cellular angiofibromas have good prognosis, despite some risk of relapse. The authors present the case of a 49-year-old woman with a bulky right vulvar lesion, for which the preoperative diagnosis was a Bartholin cyst, but the histological and immunohistochemical evaluation yielded a CA.

Pathways of IFN-alpha Activation in Patients with Cervical Intraepithelial Neoplasia (CIN)

Abstract Objective The aim of the present study was to compare the local and systemic expression of the factors linked to the interferon alpha (IFN-α) activation pathway in different degrees of cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods A total of 128 patients with CIN I, CIN II, CIN III and cervical cancer was evaluated. The real-time polymerase chain reaction (RT-PCR) technique was used to evaluate the gene expression of IFNR1, IFNR2, IFN-α, oligoadenylate synthase (2'5′OAS), cytokine signal suppressor 1 (SOCS) 1, SOCS3, signal transducer and transcription activator 1 (STAT1), and IRF9 from 128 biopsies. A total of 46 out of 128 samples were evaluated by flow cytometry for IFNAR1, IFNAR2, STAT1, IRF7 and IFN-α in peripheral blood cells. Results Patients with CIN II and III (63 samples) had a low local expression of IFNR1, but not IFNR2. Patients with some degree of injury showed high expression of SOCS1 and SOCS3. Systemically, patients with CIN II and III (20 samples) had a significant increase in IFNR1, IFNR2, STAT1, IRF7, and IFN-α in helper, cytotoxic T lymphocytes, and in monocytes. Conclusion Patients with high-grade lesions have increased systemic expression of IFN-α and its activation pathways in helper and cytotoxic T lymphocytes, as well as in monocytes due to an exacerbation of the immune response in these patients. This phenomenon is not accompanied by resolution of the lesion due to a defect in the IFN-α activation pathway that revealed by low local IFNAR1 expression and high local expression of SOCS1 and SOCS3.

Colposcopic Findings and Diagnosis in Low-Income Brazilian Women with ASC-H pap Smear Results

Abstract Objective To determine the accuracy of colposcopy findings in diagnosing cervical intraepithelial neoplasia (CIN) in women with an atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) pap smear result and analyze whether the prevalence of HSIL and cancer correlates with sociodemographic risk factors and specific colposcopic findings. Methods Colposcopic findings and sociodemographic risk factors were analyzed as possible predictors of a CIN 2 or worse diagnosis in women with an ASC-H pap smear result. Results Accuracy of the colposcopic impression was 92%, sensitivity was 91.6%, and specificity was 93.1%, with a positive predictive value of 96.4% and negative predictive value of 84.3%. Diagnosis of CIN 2 or worse was more frequent in patients with a previous history of cervical dysplasia and pre-menopausal patients. Identification of major colposcopic findings, dense acetowhite epithelium, coarse mosaicism, and punctuation correlated significantly with CIN 2 or worse. Conclusion Colposcopy performed by an experienced examiner can accurately differentiate patients with CIN 1 or less from patients with CIN 2 or worse. Diagnosis of CIN 2 or worse was more frequent in patients with a previous history of cervical dysplasia and pre-menopausal patients. The degree of acetowhite changes was the best colposcopic feature to predict CIN2 or worse.

Call to Eliminate Cervical Cancer in the Next Decade with a Focus on Brazil

Association of Swede Score and 2011 IFCPC Nomenclature in Women with Abnormal Cytology

Abstract Objective To assess the association between two colposcopic indices, the Swede score and the 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC) Nomenclature as well as to determine the efficacy of the Swede score with cutoffs of 7 and 8. Methods In the present cross-sectional pilot study, 34 women who had at least 1 colposcopy-directed biopsy due to abnormal cytology were enrolled. The colposcopic findings were scored by both the Swede score and the 2011 IFCPC Nomenclature and were compared with each other. The Kappa coefficient and the McNemar test were used. Accuracy, sensitivity, specificity, and positive and negative predictive values (NPV and PPV, respectively) were calculated, as well as the effectiveness with cutoffs of 7 and 8 in identifying cervical intraepithelial neoplasm (CIN) 2+ when using the Swede score. Results The correlation between the 2 colposcopic indices was 79.41%. The Kappa coefficient and the McNemar p-value were 0.55 and 0.37, respectively. The IFCPC Nomenclature had sensitivity, specificity, accuracy, PPV, and NPV of 85.71, 55.00, 67.64, 57.14, and 84.61%, respectively. The Swede score had sensitivity, specificity, accuracy, PPV, and NPV of 100, 63.15, 79.41, 68.18, and 100%, respectively. A Swede score cutoff of 7 for CIN 2+ detection had a specificity of 94.73%, while with a cutoff of 8 it increased to 100%. The sensitivity for both values was 60%. The PPV and NPV for cutoffs of 7 and 8 were 90 and 75 and 100 and 76%, respectively. Conclusion Although both colposcopic indices have good reproducibility, the Swede score showed greater accuracy, sensitivity, and specificity in identifying CIN 2 + , especially when using a cutoff of 8.

The Effects of Hysterectomy on Urinary and Sexual Functions of Women with Cervical Cancer: A Systematic Review

Abstract Objective This systematic review aims at describing the prevalence of urinary and sexual symptoms among women who underwent a hysterectomy for cervical cancer. Methods A systematic search in six electronic databases was performed, in September 2019, by two researchers. The text search was limited to the investigation of prevalence or occurrence of lower urinary tract symptoms (LUTS) and sexual dysfunctions in women who underwent a hysterectomy for cervical cancer. For search strategies, specific combinations of terms were used. Results A total of 8 studies, published between 2010 and 2018, were included in the sample. The average age of the participants ranged from 40 to 56 years, and the dysfunctions predominantly investigated in the articles were urinary symptoms (n = 8). The rates of urinary incontinence due to radical abdominal hysterectomy ranged from 7 to 31%. The same dysfunction related to laparoscopic radical hysterectomy varied from 25 to 35% and to laparoscopic nerve sparing radical hysterectomy varied from 25 to 47%. Nocturia ranged from 13%, before treatment, to 30%, after radical hysterectomy. The prevalence rates of dyspareunia related to laparoscopic radical hysterectomy and laparoscopic nerve sparing radical hysterectomy ranged from 5 to 16% and 7 to 19% respectively. The difficulty in having orgasm was related to laparoscopic radical hysterectomy (10 to 14%) and laparoscopic nerve sparing radical hysterectomy (9 to 19%). Conclusion Urinary and sexual dysfunctions after radical hysterectomy to treat cervical cancer are frequent events. The main reported disorders were urinary incontinence and dyspareunia.

Cytology-based Screening for Anal Intraepithelial Neoplasia in Immunocompetent Brazilian Women with a History of High-Grade Cervical Intraepithelial Neoplasia or Cancer

Abstract Objective To determine the prevalence and possible variables associated with anal intraepithelial neoplasia and anal cancer in immunocompetent women with high-grade cervical intraepithelial neoplasia. Methods A cross-sectional study involving immunocompetent women with a histological diagnosis of high-grade cervical intraepithelial neoplasia and cervical cancer, conducted between January 2016 and September 2020. All women underwent anal cytology and answered a questionnaire on characterization and potential risk factors. Women with altered cytology were submitted to anoscopy and biopsy. Results A total of 69 women were included in the study. Of these, 7 (10.1%) had abnormal anal cytology results: (high-grade lesion, atypical squamous cells of undetermined significance, and atypical squamous cells, cannot exclude high-grade lesions: 28,5% each; low grade lesion: 14,3%). Of the anoscopies, 3 (42.8%) showed alterations. Of the 2 (28,5% of all abnormal cytology results) biopsies performed, only 1 showed low-grade anal intraepithelial neoplasia. The average number of pregnancies, vaginal deliveries, and abortions was associated with abnormal anal cytology. However, the highest mean regarding the cesarean sections was associated with normal cytology. Conclusion The prevalence of anal intraepithelial neoplasia was compatible with data from recent studies, especially those conducted in Brazil. Opportunistic screening for anal intraepithelial neoplasia in this high-risk population should be considered. Anal cytology is suitable for this purpose, due to its low cost and feasibility in public health services.

Human papillomavirus vaccination for adult women

Cervical Intraepithelial Neoplasia: Analyzing the Disease Present Exclusively in the Endocervical Canal

Abstract Objective To evaluate the role of cervical cytology (Pap smear) in the diagnosis of cervical intraepithelial neoplasia 2 or greater (CIN2 + ), presented exclusively in the endocervical canal, the clinical-epidemiological characteristics of this lesion, the necessary length of canal to be removed to treat, and the rate of invasive lesion hidden in the endocervical canal. Methods Cross-sectional study, by database analysis, of patients with abnormal cytology (high-grade squamous intraepithelial lesion [HSIL]), without visible colposcopy lesion, submitted to loop electrosurgical procedure (LEEP) to evaluate the association of cytology results with the histological product of the conization, to identify the epidemiological characteristics of endocervical lesion and clinical evolution, using a p-value &lt; 0.05 and 95% CI. Results In 444 cases, the Pap smear sensitivity for CIN2+ diagnosis was 75% (95% CI: 69.8–79.7), specificity was 40% (95% CI: 30.2–49.5), and the prevalence rate of histological lesion was 73% (95% CI: 70.1–78.7). There was a higher prevalence of CIN2+ in women over 42 years old and invasive cancer in those over 56 years old (p &lt; 0.001), and it was necessary to remove 2.6 cm in length of the canal to reduce the chance of recurrence (p &lt; 0.006). The rate of invasive cancer was 2.7%. Conclusion Cytology was related to a high prevalence to histological lesion (73%) in the diagnosis of CIN2+ in the endocervical disease; older patients presented a higher relationship with histological lesions in the canal disease, and it was necessary to remove an average of 2.6 cm in length of the endocervical canal to avoid the persistence and progression of CIN. The rate of occult neoplasia in the endocervical canal was 2.7%.

Cervical Cancer Screening with HPV Testing: Updates on the Recommendation

AbstractThe present update is a reassessment of the 2018 ‘Guidelines for HPV-DNA Testing for Cervical Cancer Screening in Brazil’ (Zeferino et al.)9, according to the changes observed in new international guidelines and knowledge updates. The most relevant and recent guidelines were assessed. Questions regarding the clinical practice were formulated, and the answers considered the perspective of the public and private sectors of the Brazilian health system. The review addressed risk-based strategies regarding age to start and stop screening, the use of cytology and colposcopy to support management decisions, treatment, follow-up strategies, and screening in specific groups, including vaccinated women. The update aims to improve the prevention of cervical cancer and to reduce overtreatment and the misuse of HPV testing.

Analysis of the Excess of Papanicolaou Tests in Brazil from 2006 to 2015

Abstract Objective To analyze the quantity of cervical smears, also designated Papanicolaou tests, between 2006 and 2015 in all the Federal units of Brazil, as well as to verify the quantity of exams collected outside the recommended age range and the economic impact of such excess. Methods The data was collected from the Ministry of Health's database called Sistema de Informação do Câncer do Colo de Útero (SISCOLO), which contains all the test results collected nationwide by the Unified Health System (SUS, in the Portuguese acronym). From that, the number of exams and the age range of the women who underwent them were analyzed; besides, these numbers were stratified according to the state of where the exam was performed. The quantity of exams collected outside the recommended age range was verified, and, so, the economic impact generated was noted. Results Between 2006 and 2015, 87,425,549 Papanicolaou tests were collected in Brazil. Of these, 20,215,052 tests were collected outside the age range recommended by the Brazilian Ministry of Health; this number corresponded to 23.12% of all exams. From such data, considering that each Pap smear collected by SUS generates a cost of BRL 7.30 to the government, according to the information in the Tabela SUS dated September 2018, there was a total charge of BRL 147,569,880 for tests collected outside the protocol. Conclusion In Brazil, according to the Ministry of Health's protocol about the recommended practices on collecting Pap smears, whose newest edition dates of 2016, it is recommended that Pap smears are collected in women from a specific age range, in whom the potential diagnosing advantages overcome the onus of overdiagnosis or of a lesion with great regression potential. However, such protocols have not been correctly followed, promoting more than 20 million tests in excess, and an exorbitant cost for the Brazilian public health system. It is relevant to take measures to correctly use the official protocol, reducing the patients risks, as well as the economic impact for SUS.