Julio Cesar Teixeira

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.

Diagnostic performance and clinical utility of p16 immunostaining in a population-based HPV DNA screening program

This study aimed to evaluate p16 expression and its clinical utility in cervical biopsies from women who tested positive for high-risk human papillomavirus (HPV) in a real-world screening program, assessing its correlation with HPV genotype, lesion grade, clinical management, and diagnostic upgrading. We conducted a diagnostic test study nested within the first round (2017-2022) of a population-based HPV DNA screening program in a Brazilian municipality. Women who tested positive for HPV were referred for colposcopy, and those who underwent cervical biopsy with p16(INK4a) immunohistochemistry were included. We analyzed age, HPV results, biopsy diagnoses, p16 status, procedures, and clinical outcomes using the χ Among 696 biopsies, 48.4% were p16-positive. Positivity increased with lesion severity, from 14.3% in negative biopsies to 80.0% in cervical intra-epithelial neoplasia grade 2 and 95.1% in cervical intra-epithelial neoplasia grade 3/adenocarcinoma in situ (p < .001). No significant association was found between p16 and specific HPV genotypes (43·4%-60%), although 73% of p16-positive carcinomas were linked to HPV16/18. Excisional treatment was performed in 61.7% of p16-positive cases versus 7.5% of p16-negative cases (p < .001). Cervical intra-epithelial neoplasia grade 2 or worse was diagnosed in 69.4% of p16-positive cases (p < .001), with diagnostic upgrading 7 times more frequent than in p16-negative cases (19.9% vs 2.8%; p < .001). p16 showed a positive predictive value of 69% and a negative predictive value of 90% for cervical intra-epithelial neoplasia grade 2 or worse detection, reaching 91.6% in the non-HPV16/18 sub-group. The regression analysis confirmed p16 expression with 20-fold higher odds for significative cervical lesions (odds ratio 20.2, 95% confidence interval 13.3 to 30.6, p < .001). Systematic p16 assessment in population-based screening improves risk stratification, diagnostic accuracy, and treatment allocation. These findings support integrating p16 into cervical cancer prevention strategies, particularly, in resource-limited settings where optimizing diagnostic precision and treatment balance is crucial.

Clinical Performance of a Liquid Preservation Medium for Cervicovaginal Samples in DNA‐HPV Testing and Liquid‐Based Cytology for Cervical Cancer Screening

ABSTRACTIntroductionCervical cancer remains a significant global health concern, primarily associated with persistent infections by high‐risk human papillomavirus (hr‐HPV). As screening programmes evolve from traditional cytology to DNA‐HPV testing, the need for a liquid medium that maintains the integrity of cervical samples for biomolecular analysis and cytology becomes critical.MethodsThis study evaluated the performance of the candidate liquid preservation medium (PM) Cytoliq for cervical samples intended for DNA‐HPV testing and liquid‐based cytology (LBC), in comparison with the reference PM, PreservCyt‐ThinPrep. A total of 112 women aged 18–64 years underwent routine gynaecological examinations, with paired cervical samples preserved in both PM for HPV testing and genotyping (Cobas HPV test), and LBC. The study aimed for a sensitivity greater than 90% in detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+), moderate to high agreement in HPV testing results (Kappa index &gt; 0.70) and adequate performance in LBC.ResultsThe candidate PM exhibited non‐inferior performance relative to the reference PM. DNA‐HPV testing showed a 94.5% agreement rate (Kappa = 0.88) and a sensitivity of 92.9% for CIN2+ detection. Additionally, the candidate PM performed well in LBC smear production, with no significant differences in cytological diagnoses. The agreement in LBC diagnoses was 94.0% (Kappa = 0.79) with the ThinPrep processor and 91.8% (Kappa = 0.63) with the Cytoliq processor.ConclusionThe Cytoliq PM demonstrated comparable efficacy to the reference for DNA‐HPV testing and LBC, supporting its potential as an alternative preservation medium in cervical cancer screening programmes.

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.

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

Human papillomavirus vaccination for adult women

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.

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