Cervical Intraepithelial Neoplasia grade 2 biopsy: Do p16INK4a and Ki-67 biomarkers contribute to the decision to treat? A cross-sectional study.

Background: Managing cervical intraepithelial neoplasia grade 2 (CIN2) is challenging, considering the CIN2 regression rate, perinatal risks associated with excisional procedures, and insufficient well-established risk factors to predict progression.

Objectives: To determine the ability of p16INK4a and Ki-67 staining in biopsies diagnosed with CIN2 to identify patients with higher-grade lesions (CIN3 or carcinoma).

Design And Setting: Cross-sectional study conducted at a referral center for treating uterine cervical lesions.

Conventional cytologic diagnosis of human papillomavirus-induced anal intraepithelial neoplasia: The experience of a referral center in Rio de Janeiro, Brazil.

Background: Screening of anal cancer is rarely available or performed in Brazil. This study analyzes the diagnostic performance of conventional cytology (CC) in the prevention of anal cancer in a coloproctology and gynecology outpatient clinics in a public hospital in Rio de Janeiro, Brazil.

Methods: From 2005 to 2017, 1066 conventional cytological samples were collected.

Negative histology in cervical specimens obtained with the "see and treat" method among women at a referral center in Rio de Janeiro, Brazil: a cross-sectional study.

Background: According to the Brazilian Guidelines on Cervical Cancer Screening, women with cytopathologic diagnosis of high-grade intraepithelial lesion, abnormal colposcopic findings, fully visible squamocolumnar junction and age 25 years or older should be treated at the first visit ("see and treat-S&T"). The main limitation to this approach is the risk of overtreatment, identified by histology without preinvasive lesion. The objectives of this study were to identify the overtreatment rate in women undergoing S&T in cervical cancer prevention at a referral center with extensive experience with the method and to detect possible factors associated with this rate.

A prognostic value of CD45RA, CD45RO, CCL20 and CCR6 expressing cells as 'immunoscore' to predict cervical cancer induced by HPV.

The interplay between cervical cancer (CC) and immune cells, mainly intratumoral lymphocytes, has a pivotal role in carcinogenesis. In this context, we evaluated the distribution of CD45RA and CD45RO cells as well as CCR6 and CCL20 cells in intraepithelial (IE) and marginal stroma (MS) areas from cervical intraepithelial neoplasia (CIN) I-III, and CC as 'immunoscore' for HPV-induced CC outcome. We observed increased CD45RA and CD45RO cells distribution in IE and MS areas in the CC group compared to CIN groups and healthy volunteers.

Accuracy of endocervical cytological tests in diagnosing preinvasive lesions of the cervical canal in patients with type 3 transformation zone: a retrospective observational study.

Background: Cervical cancer screening in Brazil is done using Pap smears. Women who are most likely to have a preinvasive lesion or cervical cancer are immediately referred for colposcopy.

Objective: The aim of this study was to evaluate the diagnostic performance of endocervical cytological tests in diagnosing preinvasive cervical lesions in women with initial high-grade squamous intraepithelial lesions (HSIL), or atypical squamous cells in which high-grade lesions could not be ruled out (ASC-H), or atypical glandular cells (AGC), and whose colposcopy did not show any abnormalities, with no fully visible transformation zone (types 2 and 3).

[Parameters for programming line of care procedures for cervical cancer in Brazil].

The study estimated parameters for planning and programming the supply of procedures for screening, diagnostic workup, and treatment of precursor lesions of uterine cervical cancer. These estimates were used as the basis for assessing the adequacy of Brazil's production of procedures performed by the Brazilian Unified National Health System (SUS) in 2017. Estimates were calculated using as the reference the recommended management in the national screening guidelines.

single nucleotide polymorphisms are not associated with cervical HPV-induced pre-malignant lesion but regulate cervical TNFR1 expression.

TNF-α is involved in HPV infection control by triggering cell signaling through binding in specific receptors TNFR1 and TNFR2. Genetic polymorphisms in these receptors may influence TNF-α signaling. Herein, we investigated rs767455 and rs2234649 single nucleotide polymorphisms, and TNFR1 protein expression in cervical squamous intraepithelial lesions (SIL) to identify their role in cervical pre-malignant development.

Guidelines for HPV-DNA Testing for Cervical Cancer Screening in Brazil.

Evidence-based clinical guidelines ensure best practice protocols are available in health care. There is a widespread use of human papillomavirus deoxyribonucleic acid (HPV-DNA) tests in Brazil, regardless of the lack of official guidelines. On behalf of the Brazilian Association for the Lower Genital Tract Pathology and Colposcopy (ABPTGIC, in the Portuguese acronym), a team of reviewers searched for published evidence and developed a set of recommendations for the use of HPV-DNA tests in cervical cancer screening in Brazil.

Hybrid capture as a tool for cervical lesions screening in HIV-infected women: insights from a Brazilian cohort.

Introduction: Cervical cancer remains an important burden for HIV-infected women in the era of combination antiretroviral therapy. Recommendations for cervical screening in these women diverge and may include high-risk HPV (HRHPV) testing. We aimed to evaluate the clinical usefulness of a single HRHPV testing for cervical screening of HIV-infected women.

HPV vaccines: a controversial issue?

Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects.

Roles of CDKN1A gene polymorphisms (rs1801270 and rs1059234) in the development of cervical neoplasia.

The CDKN1A gene product is a p53 downstream effector, which participates in cell differentiation, development process, repair, apoptosis, senescence, migration, and tumorigenesis. The objective of our study was investigated the importance of two polymorphisms in the CDKN1A gene, rs1801270 (31C>A) and rs1059234 (70C>T), for the development of cervical lesions in a Southeastern Brazilian population (283 cases, stratified by lesion severity, and 189 controls). CDKN1A genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and/or DNA sequencing.

Time trend analysis of cervical high-risk human papillomavirus (HPV) in HIV-infected women in an urban cohort from Rio de Janeiro, Brazil: the rise of non-16/18 HPV.

Objectives: HIV-infected women are at increased risk of human papillomavirus (HPV) infection. Time trends in annual prevalences of cervical high-risk human papillomavirus (HR-HPV) genotypes among a non-vaccinated, HIV-infected female cohort in urban Brazil were assessed for the period 2006-2012.

Methods: Cervical specimens were collected for HPV genotyping yearly between January 2006 and December 2012 in a cross-sectional analysis of participants aged ≥18 years enrolled in the Women's HIV Cohort at Fiocruz in Rio de Janeiro, Brazil.

Preinvasive and invasive disease in women with cytological diagnosis of high-grade lesion and high-grade lesion cannot exclude microinvasion.

Background: Cervical cancer is the third most common cancer in Brazil and has a high potential for prevention and cure. The prevalence of invasive and preinvasive disease in women with cytological diagnosis of high-grade lesion - cannot exclude microinvasion (HSIL-micro) is not known.

Methods: This cross-sectional study used a cytology lab database to identify women with HSIL-micro and HSIL referred to two colposcopic units from June 2006 to December 2012.

HPV vaccines: their pathology-based discovery, benefits, and adverse effects.

The discovery of the human papillomavirus (HPV) vaccine illustrates the power of in situ-based pathologic analysis in better understanding and curing diseases. The 2 available HPV vaccines have markedly reduced the incidence of cervical intraepithelial neoplasias, genital warts, and cervical cancer throughout the world. Concerns about HPV vaccine safety have led some physicians, health care officials, and parents to refuse providing the recommended vaccination to the target population.

Polymorphism in apoptotic BAX (-248G>A) gene but not in anti-apoptotic BCL2 (-938C>A) gene and its protein and mRNA expression are associated with cervical intraepithelial neoplasia.

HPV is associated with cervical cancer and plays a crucial role in tumor formation. Apoptosis is regulated by different pathways involving genes that either promote (BCL2 gene) or inhibit (BAX gene) cell death. Our goal was to determine whether the BCL2-938C>A (rs2279115) and BAX-248G>A (rs4645878) single nucleotide polymorphisms (SNPs) are associated with squamous intraepithelial neoplasia (SIL) risk, and whether their phenotypic expression was impaired in these lesions.

A comparison between type 3 excision of the transformation zone by straight wire excision of the transformation zone (SWETZ) and large loop excision of the transformation zone (LLETZ): a randomized study.

Background: The management of preinvasive cervical lesions has the objective to ensure the absence of invasive lesions and to prevent progression to cancer. Excisional procedures have been preferred to treat these lesions as they report the presence of unsuspected invasive lesions and the status of surgical margins, allowing inferring full excision when such are free of disease. The purpose of this study is to determine whether Straight Wire Excision of the Transformation Zone (SWETZ) is a better alternative than Large Loop Excision of the Transformation Zone (LLETZ-cone) as a type 3 excision of the Transformation Zone (TZ) to reduce incomplete excision and concerning other outcomes of surgical interest.

Large loop versus straight-wire excision of the transformation zone for treatment of cervical intraepithelial neoplasia: a randomised controlled trial of electrosurgical techniques.

Objective: To compare two electrosurgical techniques, straight-wire excision of transformation zone (SWETZ) with large loop excision of transformation zone, as a cone procedure (LLETZ-cone), for the treatment of cervical intraepithelial neoplasia (CIN), when disease is present at the cervical canal.

Design: Randomised controlled trial.

Setting: Two public hospitals, one in Rio de Janeiro, Brazil and one in Dublin, Ireland.

Effects of MDM2 promoter polymorphisms on the development of cervical neoplasia in a Southeastern Brazilian population.

We investigated the importance of two adjacent functional polymorphisms in the Murine Double Minute 2 (MDM2) gene, SNP285 G > C and SNP309 T > G, for the development of cervical lesions in a Southeastern Brazilian population (293 cases and 184 controls). MDM2 genotyping was performed by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) and/or DNA sequencing. MDM2 SNP309 has potential as a biomarker of cervical neoplasia in non-smokers, patients with family history of cancer, or those who had late sexual debut (>16 years).

Correlation of MCM2 detection with stage and virology of cervical cancer.

Unlabelled: The highly conserved mini-chromosome maintenance proteins (MCM) are important in the initiation of DNA replication. Few studies have correlated MCM expression with the progression of cancer.

Objectives: (i) To analyze the expression of MCM2 in cervical cancer; (ii) to correlate MCM2 expression with the clinical tumor staging according to FIGO classification, and (iii) to relate HPV type to MCM2 expression.

Association of CDKN2A polymorphisms with the severity of cervical neoplasia in a Brazilian population.

Variants of p16(INK4a) and p14(ARF), encoded by the CDKN2A locus, may respond differently to the presence of human papillomavirus (HPV). We investigated the potential association of two CDKN2A polymorphisms, 500C > G (rs11515) and 540C > T (rs3088440), with cervical neoplasia in patients with cervical lesions and healthy controls (n = 492). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single-strand conformation polymorphism (SSCP) and/or DNA sequencing techniques were employed for genotyping.

Recurrence of cervical intraepithelial neoplasia in human immunodeficiency virus-infected women treated by means of electrosurgical excision of the transformation zone (LLETZ) in Rio de Janeiro, Brazil.

Context And Objective: Human immunodeficiency virus (HIV)-infected women have higher incidence, prevalence, persistence and recurrence of pre-invasive cervical lesions (CIN II or III). The aim here was to investigate the risk of recurrence of CIN II/III among HIV-infected women (HIV+) and uninfected women in a cohort treated by means of large-loop excision of the transformation zone (LLETZ).

Design And Setting: Cohort study conducted at Instituto Fernandes Figueira/Fundação Oswaldo Cruz (IFF/Fiocruz).

Immunohistochemical expression of cyclin D1, p16Ink4a, p21WAF1, and Ki-67 correlates with the severity of cervical neoplasia.

High-risk human papillomaviruses are closely associated with cervical cancer and its precursor lesions through interactions between the E6 and E7 oncoproteins and the cell-cycle regulatory proteins, such as p53 and pRb, respectively. As other molecules involved in the cell-cycle control seem to be important for human papillomavirus (HPV)-mediated cervical carcinogenesis, we have analyzed the expression of p53, p21, p16, cyclin D1, and Ki-67 and the presence of HPV (HPV pool and HPV-16) by immunohistochemical studies using tissue microarray in low squamous intraepithelial lesions (n=50), high squamous intraepithelial lesions (n=98), and cervical carcinoma (n=18). We have found a significant increase in the expression of p16 and p21 (P<0.

Balance of apoptotic and anti-apoptotic marker and perforin granule release in squamous intraepithelial lesions. HIV infection leads to a decrease in perforin degranulation.

Cell-mediated cytotoxicity plays an important role in the regulation to HPV-associated cervical intraepithelial neoplasia. HIV co-infection is related to poorer prognosis and more rapid clinical progression to cancer. We evaluated the presence of cervical inflammatory cells, apoptotic (Bax, Bcl-2, FasL, NOS2, perforin) markers and the degranulating expressing cell marker (CD107a) in low and high squamous intraepithelial lesions (LSIL and HSIL, respectively) from HIV-negative and -positive women.

A comparative analysis of clinical and molecular factors with the stage of cervical cancer in a Brazilian cohort.

Unlabelled: Cell cycle protein expression plays an important role in the pathophysiology of cervical cancer. However, few studies have attempted to correlate the use of these biomarkers with the clinical progression of the tumor.

Objectives: 1) To analyze the expression of Ki-67, p53 and p16(INK4a) in cervical cancer, 2) to correlate the relative expression of these proteins as well as clinical parameters with the stage of disease, and 3) to determine the HPV DNA prevalence and subtype distribution.