Luiz Carlos Zeferino

Objective: This study aimed to verify the relation between gastrin-releasing peptide receptor (GRPR), oncogenic Human Papillomavirus (HPV) and cervical lesions severity. Methods: 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 […] Abstract Objective: This study aimed to verify the relation between gastrin-releasing peptide receptor (GRPR), oncogenic Human Papillomavirus (HPV) and cervical lesions severity. Methods: 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 […]

Objective: To analyze the prognosis of patients with breast cancer who developed trastuzumab-induced cardiotoxicity and to analyze factors associated with and resulting from cardiotoxicity. Methods: This was a retrospective cohort study that included 255 HER2-positive breast cancer patients who received adjuvant trastuzumab therapy. The inclusion criteria were a diagnosis of HER2-positive breast cancer and […] Abstract Objective: To analyze the prognosis of patients with breast cancer who developed trastuzumab-induced cardiotoxicity and to analyze factors associated with and resulting from cardiotoxicity. Methods: This was a retrospective cohort study that included 255 HER2-positive breast cancer patients who received adjuvant trastuzumab therapy. The inclusion criteria were a diagnosis of HER2-positive breast cancer and […]

The 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.

Objective The present study assesses the implementation and the impact after 2 years of a school-based human papillomavirus (HPV) vaccination program in a Brazilian city. Methods A prospective study assessing the implementation of the program, offering quadrivalent HPV vaccine in two annual doses to girls and boys aged from 9 to 10 years old. The program was started in the city of Indaiatuba, state of São Paulo, Brazil, in 2018, and had authorization from the National Immunization Program. The number of HPV vaccine first doses applied and the coverage in 2018 was calculated and compared to the year 2017. There were described events that have influenced the results. Results The program invited 4,878 children through schools (87.1% of the target population), and 7.5% refused vaccination. Several concurrent events required or competed for health professionals of the vaccination teams. The coverage of the first dose (between 9 and 10 years old) was 16.1% in 2017 and increased to 50.5% in 2018 (p < 0.0001). The first dose in all ages increased 78% in 2018 compared with 2017 (6,636/3,733). Competing demands over the program continued in 2019, and the first dose coverage dropped (26.9%). For 2020, a municipal law instituted school-based vaccination and the creation of dedicated teams for vaccination, and these strategies are waiting to be tested. Conclusion School-based annual HPV vaccination in children between 9 and 10 years old was feasible and increased vaccination coverage, regardless of gender, although the program was vulnerable to competing events.

Because of its role in preserving DNA/RNA stability, there is an increasing number of studies addressing the relationship between Fused in Sarcoma (FUS) expression and cancer. However, the disparity in FUS/FUS oncogenic vs. tumor-suppressive roles may be attributed to the complex molecular pathways associated with FUS regulation in different cancer types, and its role in cervical carcinogenesis remains largely unexplored. Methods: We determined FUS protein expression in specimens of 61 patients with advanced cervical cancer. Long-term (> 10 years) clinical follow-up data for these patients were available, and we determined disease-free, cancer-related and overall survival as related to FUS expression. Results: There were no significant associations between FUS expression and patients’ age, tumor grade, and acute/late toxicity events related to treatment (either radiation alone or chemoradiation). However, multivariate Cox regression analysis for disease-free survival (recurrence), overall survival (death) and cancer-related survival showed that patients with high average FUS expression fared significantly better than their counterparts with low average FUS expression, both in terms of disease-free survival (HR = 0.31; 95%CI 0.12 to 0.77; p = 0.01) and cancer-related survival (HR = 0.41; 95%CI 0.17 to 0.98; p = 0.04). Conclusions: Our study shows that high FUS protein expression in advanced cervical cancer specimens is a potent harbinger of better prognosis, and can as such be used in clinical practice to help characterize patients and, possibly, plan treatment and follow-up strategies.

This paper searches an ideal cone height for stage definition and safe treatment of cervical microinvasive squamous carcinoma stage IA1 (MIC IA1), avoiding excessive cervix resection, favoring a future pregnancy. A retrospective study was performed involving 562 women with MIC IA1, from 1985 to 2013, evaluating cone margin involvement, depth of stromal invasion, lymph vascular invasion, conization height, and residual uterine disease (RD). High-grade squamous lesions or worse detection was considered recurrence. Univariate and multivariate regression analyses were performed, including age, conization technique (CKC, cold-knife, or ETZ, excision of transformation zone), and pathological results. Conization height to provide negative margins and the risk of residual disease were analyzed. Conization was indicated by biopsy CIN2/3 in 293 cases. Definitive treatments were hysterectomy (69.8%), CKC (20.5%), and ETZ (9.7%). Recurrence rate was 5.5%, more frequent in older women (p = 0.030), and less frequent in the hysterectomy group (p = 0.023). Age ≥40 years, ETZ and conization height are independent risk factors for margin involvement. For ages <40 years, 10 mm cone height was associated with 68.6% Negative Predictive Value (NPV) for positive margins, while for 15 mm and 25 mm, the NPV was 75.8% and 96.2%, respectively. With negative margins, the NPV for RD varied from 85.7–92.3% for up to 24 mm cone height and 100% from 25 mm. Conization 10 mm height for women <40 years provided adequate staging for almost 70%, with 10% of RD and few recurrences. A personalized cone height and staging associated with conservative treatment are recommended.

High superoxide dismutase 2 (SOD2) expression is associated with a poor prognosis at many cancer sites, the presence of metastases, and more advanced cervical cancer. This study aims to determine whether SOD2 protein expression is associated with the prognosis of stage IIIB cervical carcinoma. Methods: sixty-three patients with stage IIIB squamous cell cervical carcinoma were included. The evaluation of SOD2 expression by immunohistochemistry was based on a positive cell ratio score and the staining intensity score. Taking disease recurrence and death as endpoints, receiver operating characteristic curves were used to discriminate between high and low SOD2 expression. Results: high SOD2 expression was associated with recurrence (p = 0.001), distant recurrence (p = 0.002), and death (p = 0.005). A multivariate analysis showed that patients with high SOD2 expression had a threefold increased risk for recurrence (HR = 3.16; 1.33–7.51) and death (HR = 2.98; 1.20–7.40) compared with patients who had low SOD2 expression. Patients with high SOD2 expression had shorter disease-free survival (p = 0.001) and overall survival (p = 0.003) than patients with low SOD2 expression. Conclusion: high SOD2 expression is a strong prognostic factor for stage IIIB squamous cell carcinoma of the cervix and could be used as a prognostic marker in women with cervical carcinoma.