RESUMO
Persistent infection with high-risk human papillomavirus (HR-HPV) is a well-established risk factor to the development of cervical intraepithelial neoplasia (CIN), a condition that can progress to cervical cancer (CC) a major health problem worldwide. Recently, there has been growing interest in exploring alternative therapies utilizing natural products, among which is the algae species Laurencia johnstonii Setchell & Gardner, 1924 (L. johnstonii), proposed for the management of precancerous lesions. The aim of this work was to determine the effect of an organic extract from L. johnstonii (ELj) in early cervical lesions (CIN 1). These CIN 1 lesions were generated in a murine model expressing the HR-HPV16 E7 oncoprotein (K14E7HPV transgenic mice) with a single exogenous hormonal stimulus using 17ß-estradiol. The histopathological studies, the determination of cell proliferation and of the apoptotic levels in cervical tissue, showed that, seven doses of ELj (30 mg/kg weight per day diluted in a DMSO-saline solution [1:7]) lead to recovery the architecture of cervical epithelium. Accordingly, in the transgenic mice it was observed a statistically significant decrease of the PCNA expression levels, a marker of cell proliferation, and a statistically significant increase in the apoptosis levels using Caspase 3 as a marker. In addition, we determined the expression levels of the tumor suppressor miR-218 and the oncomiRNA miR-21. Interestingly, our results may suggest that ELj treatment tended to restore the normal expression of both miRNAs as compared with controls being more evident in the non-transgenic induced mice. Differences of p < 0.05 were considered statistically significant through the whole study. Based on these results, we propose that the use of ELj could be an alternative for the treatment of cervical early lesions.
Assuntos
Laurencia , MicroRNAs , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Camundongos , Animais , Laurencia/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/patologia , MicroRNAs/genética , Camundongos Transgênicos , Carcinogênese , Papillomaviridae/genéticaRESUMO
Objetivo: Bolivia enfrenta serios problemas en la prevención secundaria del cáncer cervicouterino. Este estudio tiene por objetivo evaluar la eficacia y concordancia de los métodos de diagnóstico en la prevención secundaria del cáncer de cuello uterino para detectar lesiones cervicales intraepiteliales de alto grado. Métodos: sesenta y dos pacientes con una citología alterada o una prueba VPH-ar positiva complementada obligatoriamente con una citología, fueron sometidas a una colposcopia y biopsia dirigida. Aquellas pacientes con diagnósticos histopatológicos de NIC2+ en la biopsia colposcópica recibieron el tratamiento escisional correspondiente, obteniéndose muestras de tejido para su análisis histopatológico (biopsias escisionales). Los resultados de la citología e impresión colposcópica fueron comparados con los resultados histopatológicos de la biopsia colposcópica. Finalmente, los resultados histopatológicos de NIC2+ de la biopsia colposcópica fueron comparados con los resultados de la biopsia escisional. Resultados: la sensibilidad de la citología y la impresión colposcopia para detectar NIC 2+ fue de 31,43% y 80% respectivamente. La concordancia (Índice Kappa) de los resultados de la citología y la impresión colposcópica comparadas con los resultados NIC 2+ de la biopsia colposcópica fue 0,15 (leve) y 0,43 (moderado) respectivamente. Finalmente, la comparación entre los resultados histopatológicos de la biopsia colposcópica (NIC2+) y de la biopsia escisional dio una coincidencia del 68%. Conclusiones: la citología tuvo una baja eficacia y concordancia para detectar NIC 2+. La colposcopia mejora la identificación de lesiones subyacentes NIC 2+ en pacientes con citologías iguales o menores a LIE-BG.
Objectives: Bolivia faces serious problems in cervical cancer secondary prevention. This study aims to evaluate the effectiveness and concordance of diagnostic methods in the secondary prevention of cervical cancer to detect high-grade cervical intraepithelial lesions. Methods: sixty-two patients with altered cytology or a positive HR-HPV test, compulsorily complemented by cytology, underwent colposcopy and targeted biopsy. Those patients with histopathological diagnoses of CIN2+ in the colposcopic biopsy received the corresponding excisional treatment, obtaining tissue samples for histopathological analysis (excisional biopsies). The results of the cytology and colposcopy impression were compared with the histopathological results of the colposcopic biopsy. Finally, the histopathological results of CIN2+ from the colposcopic biopsy were compared with the results from the excisional biopsy. Results: the sensitivity of cytology and colposcopy impression to detect CIN 2+ was 31.43% and 80% respectively. The agreement (Kappa Index) of the results of cytology and colposcopic impression compared with the CIN 2+ results of colposcopic biopsy was 0.15 (mild) and 0.43 (moderate) respectively. Finally, the comparison between the histopathological result of the colposcopic biopsy and the excisional biopsy gave a simple percentage coincidence of 68%. Conclusions: cytology had low efficacy and concordance to detect CIN 2+. Colposcopy improves the identification of underlying CIN 2+ lesions in patients with cytology equal to or less than LIE-BG.
RESUMO
ABSTRACT 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. METHODS: In 79 women, we analyzed the correlation of p16INK4a and Ki-67 expression in CIN2 biopsies with the presence of a higher-grade lesions, as determined via histopathology in surgical specimens from treated women or via two colposcopies and two cytological tests during follow-up for untreated women with at least a 6-month interval. The expression of these two biomarkers was verified by at least two independent pathologists and quantified using digital algorithms. RESULTS: Thirteen (16.8%) women with CIN2 biopsy exhibited higher-grade lesions on the surgical excision specimen or during follow-up. p16INK4a expression positively and negatively predicted the presence of higher-grade lesions in 17.19% and 86.67% patients, respectively. Ki-67 expression positively and negatively predicted the presence of higher-grade lesions in 40% and 88.24% patients, respectively. CONCLUSIONS: Negative p16INK4a and Ki67 immunohistochemical staining can assure absence of a higher-grade lesion in more than 85% of patients with CIN2 biopsies and can be used to prevent overtreatment of these patients. Positive IHC staining for p16INK4a and Ki-67 did not predict CIN3 in patients with CIN2 biopsies.
RESUMO
The activin-follistatin system regulates several cellular processes, including differentiation and tumorigenesis. We hypothesized that the immunostaining of ßA-activin and follistatin varies in neoplastic cervical lesions. Cervical paraffin-embedded tissues from 162 patients sorted in control (n = 15), cervical intraepithelial neoplasia (CIN) grade 1 (n = 38), CIN2 (n = 37), CIN3 (n = 39), and squamous cell carcinoma (SCC; n = 33) groups were examined for ßA-activin and follistatin immunostaining. Human papillomavirus (HPV) detection and genotyping were performed by PCR and immunohistochemistry. Sixteen samples were inconclusive for HPV detection. In total, 93% of the specimens exhibited HPV positivity, which increased with patient age. The most detected high-risk (HR)-HPV type was HPV16 (41.2%) followed by HPV18 (16%). The immunostaining of cytoplasmatic ßA-activin and follistatin was higher than nuclear immunostaining in all cervical epithelium layers of the CIN1, CIN2, CIN3, and SCC groups. A significant decrease (p < 0.05) in the cytoplasmic and nuclear immunostaining of ßA-activin was detected in all cervical epithelial layers from the control to the CIN1, CIN2, CIN3, and SCC groups. Only nuclear follistatin immunostaining exhibited a significant reduction (p < 0.05) in specific epithelial layers of cervical tissues from CIN1, CIN2, CIN3, and SCC compared to the control. Decreased immunostaining of cervical ßA-activin and follistatin at specific stages of CIN progression suggests that the activin-follistatin system participates in the loss of the differentiation control of pre-neoplastic and neoplastic cervical specimens predominantly positive for HPV.
Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Papillomavirus Humano , Folistatina , Papillomaviridae/genéticaRESUMO
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 < 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.
Resumo Objetivo Tanto os tipos quanto as linhagens do Papilomavírus Humano (HPV) parecem ter diferentes capacidades carcinogênicas e estão associados a riscos variados para o desenvolvimento de neoplasia intraepitelial cervical (NIC) e câncer de colo do útero. O presente estudo tem como objetivo analisar a diversidade genética do genótipo HPV 16 nos casos de NIC2/NIC3 e câncer de colo de útero em mulheres da região Nordeste do Brasil. Métodos Estudo transversal de base hospitalar realizado na região Nordeste do Brasil no período de 2014 a 2016. A amostra foi composta por 196 casos da variante HPV-16 (59 casos de NIC2/NIC3 e 137 de câncer do colo do útero). O teste de diferença de proporção foi usado para comparar os grupos NIC2/NIC3 e câncer de colo do útero por linhagem viral em relação à prevalência da linhagem HPV-16. Foi considerada significância estatística o valor de p < 0,05. Resultados As frequências de linhagem por diagnóstico histopatológico mostraram diferença limítrofe da linhagem A no grupo NIC2/NIC3 em relação ao grupo câncer de colo de útero (p = 0,053). Por outro lado, em relação à linhagem D, houve uma proporção maior nos casos de câncer (32,8%) quando comparado ao grupo NIC2/NIC3 (16,9%) e esta diferença se mostrou estatisticamente significante (p = 0,023). Conclusão A linhagem A do HPV-16 foi a mais frequente tanto nas amostras CIN2/CIN3 quanto nas amostras de câncer de colo de útero, enquanto a linhagem D predominou no câncer de colo do útero, sugerindo uma possível associação da linhagem D de HPV-16 com câncer de colo de útero.
Assuntos
Humanos , Feminino , Papillomavirus Humano 16RESUMO
Cervical cancer is the fourth most common type of cancer in women. Worldwide, it is a public health problem with around 604,127 women diagnosed per year and 341,831 deaths. Cervical cancer and persistent high-risk human papillomavirus (HPV) infection are highly associated. However, other factors are also involved, such as viral load, HPV variants, sexual behavior, and genetic factors. The host immune response against HPV has been widely studied and it has shown associations with development of cervical cancer. The human leukocyte antigen (HLA) genes are related to the persistence of HPV infection and progression to cervical cancer because of their role in controlling T-cell mediated immune response to clear the infection. In Ecuador, there is scarce information about HLA and HPV infection with high-risk genotypes in the population. This study aimed to identify host-specific HLA alleles in women with cervical intraepithelial neoplasia (CIN) II and III, and cancer infected with HPV-16, 58, and 52. In this study, we included 51 samples previously identified as positive for HPV-16, 58, and 52 from 12 Ecuadorian provinces. As a result, we found that HLA-A*02, HLA-B*35, HLA-C*04, HLA-DRB1*04, and HLA-DQB1*03 alleles were the most frequent, these alleles have been associated with cervical cancer in previous studies; nevertheless, we did not find a statistically significant association between HLA alleles, HPV genotype, and histopathological lesion. This is a baseline study to uncover possible relationships between HLA and HPV to elucidate why this virus can develop a persistent infection in some women leading to the development of cervical cancer.
Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Equador/epidemiologia , Displasia do Colo do Útero/genética , Antígenos de Histocompatibilidade Classe I/genética , Cadeias HLA-DRB1 , Papillomaviridae/genéticaRESUMO
Las neoplasias intraepiteliales córneo-conjuntival son lesiones premalignas, mal delimitadas, de crecimiento lento y escaso potencial de malignización. Solo el 9 por ciento progresa a carcinoma invasor de células escamosas. Posee varias formas de presentación y tiene múltiples dilataciones vasculares. La displasia epitelial corneal primaria es una forma poco frecuente de neoplasia intraepitelial córnea-epitelial. Se presenta un caso clínico confirmado por estudios anatomopatológicos. En el presente estudio se observó respuesta satisfactoria luego de un mes de tratamiento tópico con 5FU, sin efectos colaterales. El seguimiento durante tres años no ha mostrado signos de recidiva(AU)
Corneal-conjunctival intraepithelial neoplasms are premalignant, poorly demarcated, slow-growing lesions with low malignant potential. Only the 9 percent progresses to invasive squamous cell carcinoma. It appears in several forms and presents multiple vascular dilatations. Primary corneal epithelial dysplasia is a rare form of corneal-epithelial intraepithelial neoplasia. We present a clinical case, confirmed by anatomopathologic studies. In the present study we observed a satisfactory response after one month of topical treatment with 5FU, with no side effects. Follow-up for three years has shown no signs of recurrence(AU)
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma in Situ/etiologia , Microscopia Confocal/métodos , Fluoruracila/uso terapêuticoRESUMO
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 pvalue< 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<0.001), and it was necessary to remove 2.6 cm in length of the canal to reduce the chance of recurrence (p<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%.
Resumo Objetivo Avaliar o papel da citologia oncótica (CO) no diagnóstico da neoplasia intraepitelial cervical 2 ou maior (NIC2+) presente exclusivamente no canal endocervical, as características clínico-epidemiológicas deste tipo de lesão, o comprimento necessário de canal a ser retirado na conização, e a taxa de lesão invasora oculta no canal endocervical. Métodos Estudo transversal, por análise de base de dados, de pacientes comcitologia alterada, sem lesão colposcópica visível, submetidas a conização por cirurgia de alta frequência (CAF), para avaliar a associação dos resultados citológicos com o produto histológico da conização, as características epidemiológicas da lesão endocervical, e evolução clínica, utilizando o valor de p<0.05 e intervalo de confiança (IC) de 95%. Resultados Nos 444 casos analisados, a sensibilidade da CO para o diagnóstico de NIC 2+ foi de 75% (IC 95%: 69.8-79.7), a especificidade foi de 40% (IC 95%: 30.2-49.5), e a taxa de prevalência de lesão histológica foi de 73% (IC 95%: 70.1-78.7). Houve maior prevalência de NIC2+ em pacientes com mais de 42 anos de idade e de neoplasia invasora naquelas commais de 56 anos (p<0.001), e foi necessário a retirada de 2.6 cm de comprimento de canal para diminuir a taxa de recidiva (p<0.006). Foi identificada uma taxa de 2.7% de neoplasia invasora. Conclusão A citologia esteve relacionada a uma alta prevalência de lesão (73%) no diagnóstico das NIC2+ na doença endocervical; quanto maior a idade, maior foi a relação da histologia com a citologia de canal, e se fez necessário retirar uma média de 2.6 cmde comprimento de canal para evitar a persistência e a progressão da NIC. A taxa de neoplasia oculta no canal endocervical foi 2.7%.
Assuntos
Humanos , Feminino , Displasia do Colo do Útero/diagnósticoRESUMO
The high-risk oncogenic human papillomavirus (HPV) has developed mechanisms for evasion of the immune system, favoring the persistence of the infection. The chronic inflammation further contributes to the progression of tissue injury to cervical cancer. The programmed cell death protein (PD-1) after contacting with its ligands (PD-L1 and PD-L2) exerts an inhibitory effect on the cellular immune response, maintaining the balance between activation, tolerance, and immune cell-dependent lesion. We evaluated 295 patients exhibiting or not HPV infection, stratified according to the location (injured and adjacent non-injured areas) and severity of the lesion (benign, pre-malignant lesions). Additionally, we investigated the role of the promoter region PDCD1 -606G>A polymorphism (rs36084323) on the studied variables. PD-1 and PDCD1 expression were evaluated by immunohistochemistry and qPCR, respectively, and the PDCD1 polymorphism was evaluated by nucleotide sequencing. Irrespective of the severity of the lesion, PD-1 levels were increased compared to adjacent uninjured areas. Additionally, in cervical intraepithelial neoplasia (CIN) I, the presence of HPV was associated with increased (P = 0.0649), whereas in CIN III was associated with decreased (P = 0.0148) PD-1 levels, compared to the uninjured area in absence of HPV infection. The PDCD1 -606A allele was rare in our population (8.7%) and was not associated with the risk for development of HPV infection, cytological and histological features, and aneuploidy. In contrast, irrespective of the severity of the lesion, patients exhibiting the mutant PDCD1 -606A allele at single or double doses exhibited increased protein and gene expression when compared to the PDCD1 -606GG wild type genotype. Besides, the presence of HPV was associated with the decrease in PDCD1 expression and PD-1 levels in carriers of the -606 A allele presenting severe lesions, suggesting that other mediators induced during the HPV infection progression may play an additional role. This study showed that increased PD-1 levels are influenced by the -606G>A nucleotide variation, particularly in low-grade lesions, in which the A allele favors increased PDCD1 expression, contributing to HPV immune system evasion, and in the high-grade lesion, by decreasing tissue PD-1 levels.
Assuntos
Infecções por Papillomavirus , Receptor de Morte Celular Programada 1 , Displasia do Colo do Útero , Alelos , Apoptose , Feminino , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Receptor de Morte Celular Programada 1/genética , Displasia do Colo do Útero/genéticaRESUMO
BACKGROUND: Factors that lead human papillomavirus (HPV) infections to persist and progress to cancer are not fully understood. We evaluated co-factors for acquisition, persistence, and progression of non-HPV-16/18 infections among HPV-vaccinated women. METHODS: We analyzed 2153 women aged 18-25 years randomized to the HPV-vaccine arm of the Costa Rica HPV Vaccine Trial. Women were HPV DNA negative for all types at baseline and followed for approximately 11 years. Generalized estimating equation methods were used to account for correlated observations. Time-dependent factors evaluated were age, sexual behavior, marital status, hormonally related factors, number of full-term pregnancies (FTPs), smoking behavior, and baseline body mass index. RESULTS: A total of 1777 incident oncogenic non-HPV-16/18 infections were detected in 12 292 visits (average, 0.14 infections/visit). Age and sexual behavior-related variables were associated with oncogenic non-HPV-16/18 acquisition. Twenty-six percent of incident infections persisted for ≥1 year. None of the factors evaluated were statistically associated with persistence of oncogenic non-HPV-16/18 infections. Risk of progression to Cervical Intraepithelial Neoplasia grade 2 or worst (CIN2+) increased with increasing age (P for trend = .001), injectable contraceptive use (relative risk, 2.61 [95% confidence interval, 1.19-5.73] ever vs never), and increasing FTPs (P for trend = .034). CONCLUSIONS: In a cohort of HPV-16/18-vaccinated women, age and sexual behavior variables are associated with acquisition of oncogenic non-HPV-16/18 infections; no notable factors are associated with persistence of acquired infections; and age, parity, and hormonally related exposures are associated with progression to CIN2+.
Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adolescente , Adulto , Costa Rica/epidemiologia , DNA , Feminino , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Humanos , Papillomaviridae , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Gravidez , Fatores de Risco , Resultado do Tratamento , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Adulto Jovem , Displasia do Colo do ÚteroRESUMO
BACKGROUND: Human papillomavirus infection is an important factor associated with cervical cancer (CC) development. The prevalence and genotype distribution vary greatly worldwide. Examining local epidemiological data constitutes an important step towards the development of vaccines to prevent CC. In this work, we studied the prevalence of HPV genotypes in women from Western Mexico with the COBAS 4800 and/or Linear Array Genotyping Test (LA). METHODS: The samples analysed in this study represent a population from Western Mexico, which includes six different states. Our approach was first to test for HPV in cervical samples from women who attended their health clinic for routine gynaecological studies (open-population, n = 3000) by utilizing COBAS 4800. Afterwards, 300 of the HPV-positive samples were randomly selected to be genotyped with LA; finally, we genotyped samples from women with cervical intraepithelial neoplasia grade 1 (CIN 1, n = 71) and CC (n = 96) with LA. Sociodemographic data of the diverse groups were also compared. RESULTS: The overall HPV prevalence among the open-population of women as determined by COBAS 4800 was 12.1% (n = 364/3000). Among the HPV-positive samples, single infections (SI) with HPV16 were detected in 12.4% (n = 45/364), SI with HPV18 were detected in 1.4%, and infection with at least one of the genotypes included in the high-risk HPV pool was detected in 74.5% of the cases. LA analysis of the samples showed that in addition to HPV genotypes 16 and 18, there was a high prevalence of HPV genotypes 59, 66, 52, 51, 39 and 56 in women from Western Mexico. With respect to the sociodemographic data, we found statistically significant differences in the number of pregnancies, the use of hormonal contraceptives and tobacco intake. CONCLUSIONS: Our data indicate that there is a high prevalence of HPV genotypes which are not covered by the vaccines currently available in Mexico; therefore, it is necessary to include HPVs 59, 66, 51, 39 and 56 in the design of future vaccines to reduce the risk of CC development. It is also essential to emphasize that the use of hormonal contraceptives and tobacco smoking are risk factors for CC development in addition to the presence of HPV.
Assuntos
Genótipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Infecções por Papillomavirus/epidemiologia , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Incidência , México/epidemiologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Prevalência , Fatores de Risco , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/virologiaRESUMO
Molecular classification of colorectal cancer is difficult to implement in clinical settings where hundreds of genes are involved, and resources are limited. This study aims to characterize the molecular subtypes of patients with sporadic colorectal cancer based on the three main carcinogenic pathways microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and chromosomal instability (CIN) in a Chilean population. Although several reports have characterized colorectal cancer, most do not represent Latin-American populations. Our study includes 103 colorectal cancer patients who underwent surgery, without neoadjuvant treatment, in a private hospital between 2008 and 2017. MSI, CIN, and CIMP status were assessed. Frequent mutations in KRAS, BRAF, and PIK3CA genes were analyzed by Sanger sequencing, and statistical analysis was performed by Fisher's exact and/or chi-square test. Survival curves were estimated with Kaplan-Meier and log-rank test. Based on our observations, we can classify the tumors in four subgroups, Group 1: MSI-high tumors (15%) are located in the right colon, occur at older age, and 60% show a BRAF mutation; Group 2: CIN-high tumors (38%) are in the left colon, and 26% have KRAS mutations. Group 3: [MSI/CIN/CIMP]-low/negative tumors (30%) are left-sided, and 39% have KRAS mutations; Group 4: CIMP-high tumors (15%) were more frequent in men and left side colon, with 27% KRAS and 7% presented BRAF mutations. Three percent of patients could not be classified. We found that CIMP-high was associated with a worse prognosis, both in MSI-high and MSI stable patients (p = 0.0452). Group 3 (Low/negative tumors) tend to have better overall survival compared with MSI-high, CIMP-high, and CIN-high tumors. This study contributes to understanding the heterogeneity of tumors in the Chilean population being one of the few characterizations performed in Latin-America. Given the limited resources of these countries, these results allow to improve molecular characterization in Latin-American colorectal cancer populations and confirm the possibility of using the three main carcinogenic pathways to define therapeutic strategies.
Assuntos
Carcinogênese/genética , Instabilidade Cromossômica/genética , Neoplasias Colorretais/genética , Instabilidade de Microssatélites , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Chile/epidemiologia , Neoplasias Colorretais/classificação , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Ilhas de CpG/genética , Metilação de DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
Silymarin, an extract from Silybum marianum (milk thistle) containing a standardized mixture of flavonolignans that ameliorates some types of liver disease and, more recently, kidney damage, could be used for the ROS-scavenging effect of these antioxidants. Furthermore, contrast-induced nephropathy (CIN) is an iatrogenic impairment of renal function in patients subjected to angiographic procedures for which there is not yet a successful preventative treatment. Recent evidence has shown that this event is related to tubular/vascular injury activated mainly by oxidative stress. However, whether this bioavailable and pharmacologically safe extract protects against CIN is not clear. We proposed to evaluate the possible protective role of the antioxidant silymarin in an experimental model of CIN. Adult male Swiss mice were separated into 6 groups and pretreated orally with silymarin (50, 200 and 300â¯mg/kg), N-acetylcysteine (200â¯mg/kg) or vehicle for 5â¯days before the CIN and control groups. Renal function was analyzed by plasma creatinine, urea and cystatin C levels. Additionally, blood reactive oxygen species (ROS) were evaluated using ROS bioavailability, protein oxidation and DNA damage. Renal oxidative damage was evaluated using apoptosis/cell viability assays and histological analysis. We showed that silymarin preserved renal function and decreased systemic and renal oxidative damage (antigenotoxic and antiapoptotic properties, respectively) in a dose-dependent manner and was superior to conventional treatment with N-acetylcysteine. Histologically, silymarin treatment also had beneficial effects on renal glomerular and tubular injuries. Therefore, silymarin prophylaxis may be an interesting strategy for the prevention of CIN.
Assuntos
Meios de Contraste/efeitos adversos , Rim/efeitos dos fármacos , Nefrite/induzido quimicamente , Nefrite/prevenção & controle , Substâncias Protetoras/uso terapêutico , Silimarina/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos , Silybum marianum/química , Nefrite/metabolismo , Nefrite/patologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/química , Silimarina/químicaRESUMO
BACKGROUND: Human Papillomavirus (HPV) infection is estimated to be the most common sexually transmitted infection. The present systematic review summarizes data regarding the prevalence of HPV and the distribution of subtypes in heterosexual male partners of women, who were diagnosed with any grade of cervical intraepithelial neoplasia (CIN). METHODS: We conducted a systematic review of the literature by Medline and Google Scholar databases using the terms "Human Papillomavirus" or "HPV" plus "men" or "male partners" or "women with CIN". We included original published English-language articles published from 1/1/2000 until 1/1/2018 that had screened male partners of women with CIN using HPV DNA testing. We excluded studies that they overlapped with other included studies or were unrelated to the study subject. RESULTS: We included a total of 12 publications, which reported the prevalence of HPV in free-clinical signs male partners of women with CIN. The largest proportion of the studies were from South America (seven studies), and the rest from Europe. The mean age of participants was 35.18 + - 3.47 years. HPV prevalence ranged from 12.9 to 86%; the total HPV prevalence among the studies was 49.1%, while ten out twelve studies (83.3%) demonstrated prevalence > 20%. Between the studies, the distribution of HPV subtypes varied on the basis of the method used, on the population and on the geographic region. A great variety of subtypes were detected, including 6, 11, 16, 18, 31, 33, 40, 42, 45, 51, 52, 53, 54, 56, 57, 58, 59, 61, 62, 66, 68, 81 and 83. In six studies the HPV 16 was the most frequent, while in two others the HPV 6 and HPV 83. CONCLUSIONS: Until now, there are not precise screening or surveillance guidelines for the management of partners of women with CIN. This population is frequently colonized by various HPV subtypes and therefore need to be screened in an effort to reduce the infection in both sexes. The screening test could include detection/identification of HPV subtypes by a molecular assay, followed by peniscopy only in the positive cases.
Assuntos
Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Europa (Continente) , Feminino , Humanos , Masculino , Programas de Rastreamento , Papillomaviridae/patogenicidade , Prevalência , Parceiros Sexuais , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/virologia , América do SulRESUMO
Anticancer regimens for Hodgkin lymphoma (HL) patients include highly genotoxic drugs that have been very successful in killing tumor cells and providing a 90% disease-free survival at five years. However, some of these treatments do not have a specific cell target, damaging both cancerous and normal cells. Thus, HL survivors have a high risk of developing new primary cancers, both hematologic and solid tumors, which have been related to treatment. Several studies have shown that after treatment, HL patients and survivors present persistent chromosomal instability, including nonclonal chromosomal aberrations. The frequency and type of chromosomal abnormalities appear to depend on the type of therapy and the cell type examined. For example, MOPP chemotherapy affects hematopoietic and germ stem cells leading to long-term genotoxic effects and azoospermia, while ABVD chemotherapy affects transiently sperm cells, with most of the patients showing recovery of spermatogenesis. Both regimens have long-term effects in somatic cells, presenting nonclonal chromosomal aberrations and genomic chaos in a fraction of noncancerous cells. This is a source of karyotypic heterogeneity that could eventually generate a more stable population acquiring clonal chromosomal aberrations and leading towards the development of a new cancer.
Assuntos
Aberrações Cromossômicas , Dano ao DNA , Instabilidade Genômica , Doença de Hodgkin/genética , Antineoplásicos/toxicidade , Células Germinativas/metabolismo , HumanosRESUMO
AIM: To evaluate cyclin-dependent kinase inhibitor 2A (CDKN2A) and cytokeratin 7 (CK7) expression in cervical intraepithelial neoplasia (CIN) formalin-fixed samples. MATERIALS AND METHODS: Staining with antibody clones G175-405 for CDKN2A and OV-TL 12/30 for CK7 were evaluated and the detection of protein expressions were compared in 147 patients with CIN. RESULTS: Clinical follow-up of patients with CIN1 and CIN2 showed that most patients had a favorable outcome. Single CDKN2A or CK7 expression and their combined expression had a greater sensitivity and negative predictive value in CIN1, corresponding to the non-development of the disease. The positive predictive value of CDKN2A was greater than that of CK7. Combined expression of CDKN2A and CK7 showed that the sensitivity, specificity, positive predictive values, and negative predictive values had their maximum index in the CIN1 group. Analysis of combined expression of CDKN2A and CK7 showed that 85.7% of patients presented unfavorable clinical outcomes, with positive expression for both markers identified in CIN2. CONCLUSION: Combined expression of CK7 and CDKN2A was associated with a better diagnosis of CIN, and negative expression in CIN1/2 groups had a greater negative predictive value for patient clinical outcome.
Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Queratina-7/metabolismo , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/metabolismo , Adolescente , Adulto , Biomarcadores Tumorais/metabolismo , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/metabolismo , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/patologia , Adulto Jovem , Displasia do Colo do Útero/patologiaRESUMO
OBJECTIVE: To evaluate the usefulness of endocervical curettage (ECC) during loop electrosurgical excision procedures (LEEPs) in predicting the risk of persistence/recurrence of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and informing clinical decision-making after LEEP. METHODS: The present retrospective study included women undergoing LEEP for CIN2+ at a teaching hospital in Chile between January 1, 2007, and December 31, 2014. Demographic, pathologic, and follow-up data were collected. Associations between predictors and treatment failure (persistent/recurrent disease) were examined; a Cox model was used to assess the effects of different variables on the failure rate. RESULTS: The analysis included 330 women with a mean follow-up of 29.4 months; 188 women underwent ECC at the time of LEEP. On multivariate analysis, a positive ECC was the only variable significantly associated with persistence/recurrence (P=0.001). In the Cox model, positive ECC (P=0.001) and positive margins (P=0.009) were independently associated with higher failure rates. When faced with positive ECC findings, clinicians tended to perform additional treatment instead of advising follow-up. CONCLUSION: Positive findings from ECC performed during LEEP were a better predictor of persistent/recurrent disease than margin status, after adjusting the individual variable effect in the Cox modelling. The performance of ECC is recommended during any LEEP performed for CIN2+; in particular, it should never be omitted if endocervical disease is suspected.
Assuntos
Curetagem/métodos , Eletrocirurgia/métodos , Displasia do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/cirurgia , Adulto , Feminino , Humanos , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Fatores de Risco , Traquelectomia/métodos , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/patologiaRESUMO
BACKGROUND: Curaçao is a Dutch-Caribbean Island located in a high-risk area for cervical cancer.Prior to introduction of a prophylactic human papillomavirus (HPV) vaccine, knowledge of the prevalence of high-risk HPV vaccine genotypes (HPV16, 18, 31, 33, 45, 52 and 58) in cervical (pre)cancer is required. OBJECTIVE: To investigate the prevalence of HPV genotypes in invasive cervical cancers (ICC) and cervical intraepithelial neoplasia (CIN) grade 1, 2 and 3 in Curaçao. METHODS: Paraffin-embedded blocks of 104 cervical cancers (89 squamous, 15 adenocarcinoma), 41 CIN3, 39 CIN2 and 40 CIN1 lesions were analysed for the presence of HPV. Sections were stained by H&E for histopathological evaluation, and DNA was extracted using proteinase K. HPV genotypes were detected using Short PCR Fragment (SPF10) PCR DNA enzyme immunoassay and a Line Probe Assay (LiPA25) . RESULTS: HPV was found in 92 (88.5%) ICC; 87 (94.6%) had a single HPV infection and 86 (93.5%) were high-risk human papillomavirus (hrHPV)-type positive.The three most common HPV types in ICC were 16 (38.5%), 18 (13.5%) and 45 (6.7%), covering 58.7%.HrHPV vaccine genotypes 16, 18, 31, 35, 45, 52 and 58 were responsible for 73.1% of ICC. For precancerous lesions, the HPV attribution was 85.4% for CIN3, 66.7% for CIN2% and 42.5% for CIN1. CONCLUSIONS: Our study, the largest in the Caribbean region in (pre)cancer, shows that the prevalence of HPV-type 16 and 18 in cervical cancer is lower compared with the world population but no differences in prevalence of these two HPV types are seen in precancerous lesions.When considering HPV vaccination in Curaçao, the relatively high contribution of non-HPV 16/18 genotypes in ICC should be taken into account.
Assuntos
Adenocarcinoma/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Infecções por Papillomavirus/epidemiologia , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adenocarcinoma/prevenção & controle , Adenocarcinoma/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alphapapillomavirus/genética , Carcinoma de Células Escamosas/prevenção & controle , Carcinoma de Células Escamosas/virologia , Curaçao/epidemiologia , Detecção Precoce de Câncer , Feminino , Genótipo , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Prevalência , Estudos Retrospectivos , Fatores de Risco , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/virologiaRESUMO
Contexto: el cono LLETZ actualmente es el tratamiento de las NIC de alto grado. La resistencia al procedimiento es argumentada por los efectos del sobretratamiento (estenosis e insuficiencia cervical), sobre todo cuando se utilizan métodos ablativos destructivos en lugar de la resección quirúrgica ambulatoria (LLETZ). Objetivo: analizar el diagnóstico y tratamiento del NIC II mediante cono y legrado en pacientes que acuden al servicio de Patología del tracto genital inferior del Hospital Oncológico SOLCA-Quito Ecuador. Sujetos y métodos: en este estudio epidemiológico descriptivo observacional de corte transversal se analizaron expediente clínicos de 820 pacientes con diagnóstico histopatológico por biopsia de NIC II; mujeres entre 17 a 82 años que acudieron al servicio de patología del tracto genital inferior sujetas a control, en estas pacientes se realizó 530 legrados. El estudio fue realizado en el Hospital Oncológico SOLCA de Quito Ecuador, de los años 2004 a 2013. Resultados: la histopatología de los conos libres de neoplasia representa el 98,66% (n=809); existen 11 casos de neoplasias residuales (1,34%). El 53,7% de casos presenta una lesión igual o mayor que en biopsia, lo que justifica el cono. Conclusión: el procedimiento de cono LLETZ tiene gran utilidad diagnóstica, terapéutica y pronóstica en mujeres que presentan NIC II y otras patologías similares. (AU)
Background: the LLETZ cone is currently the treatment of high grade NICs. The resistance to the procedure is argued by the effects of overtreatment (stenosis and cervical insufficiency), especially when destructive ablative methods are used instead of ambulatory surgical resection (LLETZ). Objective: to analyze the diagnosis and treatment of CIN II by means of cone and curettage in patients attending the pathology department of the lower genital tract of the SOLCA-Quito Ecuador Oncology Hospital. Subjects and methods: in this cross-sectional descriptive epidemiological observational study, we analyzed clinical records of 820 patients with histopathological diagnosis by CIN II biopsy; women between 17 and 82 years old who visited the pathology service of the lower genital tract subject to control, in these patients 530 catheters were performed. The study was conducted at the SOLCA Oncology Hospital of Quito, Ecuador, from 2004 to 2013. Results: the histopathology of neoplasm-free cones represents 98.66% (n = 809); there are 11 cases of residual neoplasms (1.34%). 53.7% of cases present a lesion equal to or greater than in biopsy, which justifies the cone.(AU)