ABSTRACT
Background: Cervical cancer (CC) is associated to high-risk human papillomavirus (HPV) infections, for this reason it is crucial to have sensitive and accurate HPV diagnostic tests. To date, most research is focused on HPVs within the Alphapapillomavirus (α-PVs) genus and little attention has been paid to cervical infections with other HPV genotypes, like those of the Betapapillomavirus (ß-PVs) and Gammapapillomavirus (γ-PVs) genera. The aim of this study was to determine the HPV genotypes from different genera in women with CC using Next-Generation Sequencing (NGS). Methods: The study comprised 48 HPV positive CC samples evaluated with the Linear Array HPV Genotyping test and individually sequenced by 454 NGS using PGMY09/11 and FAP primers. To determine the HPV genotypes present in each sample, the obtained sequences were compared with all HPV L1 gene reference sequences from the Papillomavirus Episteme database (PaVE). Moreover, 50 HPV positive low-grade cervical lesion samples individually genotyped with NGS were also included to determine the genotypes present preferentially in CC patients. Results: Among the 48 CC samples, 68.75% consisted of multiple HPV infections, 51 different genotypes were detected, of which 7 are still unclassified, 28 belong to α-PVs (6, 11, 16, 18, 26, 30, 33, 35, 39, 42, 43, 44, 45, 51, 52, 53, 54, 59, 62, 66, 68, 69, 70, 71, 74, 81, 102, 114), 10 to ß-PVs (5, 12, 21, 37, 38b, 47, 80, 107, 118, 122), and 6 to γ-PVs (101, 103, 123, 135, 147, 214). Among them, HPV16 was the most prevalent genotype (54.2%), followed by HPV18 (16.7%), HPV38b (14.6%), and HPVs 52/62/80 (8.3%). Some genotypes were exclusively found in CC when compared with Cervical Intraepithelial Neoplasia grade 1 (CIN1) samples, such as HPVs 5, 18, 38b, 107, 122, FA39, FA116, mSK_120, and mSK_136. Conclusions: This work demonstrates the great diversity of HPV genotypes detected by combining PGMY and FAP primers with NGS in cervical swabs. The relatively high attribution of ß- and γ- PVs in CC samples suggest their possible role as carcinogenic cofactors, but deeper studies need to be performed to determine if they have transforming properties and the significance of HPV-coinfections.
Subject(s)
Alphapapillomavirus , Papillomavirus Infections , Uterine Cervical Neoplasms , DNA, Viral/genetics , Female , Genotype , Humans , Mexico , Papillomaviridae/geneticsABSTRACT
BACKGROUND: Breast cancer is a multifactorial and heterogeneous disease with distinct molecular features and histopathologic subtypes involving different therapeutic responses and clinical outcomes. Classification of breast cancer in molecular subtypes has made possible an approach to develop therapeutic strategies in order to have a better understanding of the breast cancer development. Due to the heterogeneity of the disease, there are still features to be elucidated in the behavior, etiology and clinical outcomes of each molecular subtype in breast cancer. METHODS: Variables measured in 1,695 cases of invasive breast carcinoma were age, histopathological diagnosis, histopathological grade, expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), cell proliferation marker (Ki67) and basal cytokeratins (CK 5/6). P values were obtained using Chi square test and hazard ratios were calculated with 95% confidence intervals. RESULTS: An increase of aggressive molecular subtypes of breast cancer was observed. The mean age of incidence of breast cancer patients is decreasing, and breast cancer Patients younger than 40-years-old showed higher risk to exhibit Triple negative and Basal-like tumors. CONCLUSIONS: The mean age for this pathology is decreasing in our population and there is predominance in the differential occurrence of etiologically distinct entities of breast cancer affecting to the young women.
INTRODUCCIÓN: El cáncer de mama es una enfermedad heterogénea y multifactorial. Presenta distintas características clínicas, moleculares e histopatológicas, las cuales se asocian con la respuesta a los esquemas terapéuticos, así como al resultado clínico. La clasificación en subtipos moleculares (luminales, HER2, triple negativo y basales) ha permitido el desarrollo y aplicación de estrategias terapéuticas particulares. Sin embargo, dada la gran heterogeneidad de la enfermedad, existen aún características por elucidar en el comportamiento, etiología y resultados clínicos de cada subtipo molecular de cáncer de mama. MÉTODOS: Se obtuvieron datos de 1695 casos de cáncer de mama invasor. Se realizaron correlaciones entre las siguientes variables: edad, diagnóstico histopatológico, grado histológico, expresión del receptor de estrógenos (ER), receptor de progesterona (PR), receptor 2 del factor de crecimiento epidérmico humano (HER2), marcador de proliferación celular (Ki67) y citoqueratinas basales (CK 5/6). Los valores de p fueron calculados utilizando Chi cuadrada y el cociente de riesgo fue calculado con un intervalo de confianza de 95%. RESULTADOS: Se observó un incremento en la frecuencia de los subtipos moleculares más agresivos, así como una disminución en el valor de la media de la edad en las pacientes diagnosticadas con cáncer de mama. El análisis de la información indica que en pacientes menores de 40 años existe mayor riesgo a la presencia de tumores triple negativo o basales. CONCLUSIONES: En población mexicana, la media de edad para el diagnóstico primario de cáncer de está disminuyendo y hay mayor frecuencia de subtipos moleculares más agresivos en pacientes jóvenes.
ABSTRACT
Advances in the understanding of molecular biology of cancer have allowed that in the last 30 years some biomarkers in cancer have managed to be transferred from the laboratory to clinical practice and have been established as extremely important tools in the management of breast cancer patients. In this review are presented some biomarkers that are routinely used in clinical oncology practice and have a well-established clinical value to direct treatment and establish prognosis in patients with breast cancer, such as ER-alpha (estrogen receptor alpha), PR (progesterone receptor), HER2 (Human Epidermal Growth Factor Receptor 2), Ki-67 (Marker Of Proliferation Ki-67), and other biomarkers, such as multigenic signatures, which are used more and more frequently, due to the clinical value shown in various randomized clinical trials and for being increasingly accessible in daily clinical practice. Given the considerable importance of breast cancer in public health, it is necessary to be updated with respect to current biomarkers that have a use in clinical practice and that can serve as tools to provide patients with a more personalized treatment, as well as to know their prognosis.
Los avances en el entendimiento de la biología molecular del cáncer han permitido que en los últimos 30 años algunos biomarcadores en cáncer hayan logrado ser trasladados del laboratorio a la práctica clínica y se hayan ido estableciendo como herramientas sumamente importantes en el manejo de las pacientes con cáncer de mama. En esta revisión se presentan algunos biomarcadores de uso rutinario en la práctica clínica oncológica que tienen un valor clínico bien establecido para dirigir el tratamiento y establecer el pronóstico en pacientes con cáncer de mama, como el ER-alfa (receptor de estrógenos alfa), el PR (receptor de progesterona), el HER2 (receptor 2 del factor de crecimiento epidérmico humano), el Ki-67 (marcador de proliferación Ki-67) y otros biomarcadores, como las firmas multigénicas, las cuales son usadas cada vez con más frecuencia, debido al valor clínico mostrado en diversos ensayos clínicos aleatorizados y por ser cada vez más accesibles en la práctica clínica diaria. Dada la considerable importancia del cáncer de mama en la salud pública, es necesario estar actualizados con respecto a estos biomarcadores de uso clínico, los cuales nos pueden permitir brindarles a las pacientes un tratamiento más personalizado, así como conocer su pronóstico.
ABSTRACT
Breast cancer is the most frequent malignancy in women around the world. Its diagnosis and treatment may be accompanied by depressive symptoms. The frequency of depression in women with breast cancer may vary, ranging from < 10% to > 70%, depending on the questionnaire, type of population studied and geographic area. Depression is associated with genetic and environmental factors; the imbalance between the central nervous, endocrine and immune systems; the patient's age at diagnosis of cancer; metastasis; chemotherapy, and physical rehabilitation. Depression treatment is based on different types of approaches, such as hypnosis, meditation, music therapy and stress management. In Mexico, there are few studies about this topic. The objective of this work is to make a critical review on the scientific evidence of the relation between depression and breast cancer.
El cáncer de mama es la neoplasia maligna más frecuente en mujeres en todo en el mundo. Su diagnóstico y tratamiento puede estar acompañado de síntomas depresivos. La frecuencia de depresión en mujeres con cáncer de mama puede ser tan variada que va desde < 10% a > 70%, dependiendo del instrumento de evaluación, el tipo de población estudiada y el área geográfica. Se ha descrito que la depresión se asocia a factores genético-ambientales; desequilibrio entre los sistemas nervioso central, endócrino e inmunitario; edad de la paciente; presencia de metastasis; quimioterapia, y rehabilitación física. Su tratamiento está basado en diversos tipos de abordajes, como hipnosis, meditación, musicoterapia y manejo del estrés. En México se ha estudiado poco esta relación. El objetivo de este trabajo es realizar una revisión crítica sobre la evidencia científica de la relación entre depresión y cáncer de mama.
ABSTRACT
BACKGROUND: Human papillomavirus (HPV) is the main etiological agent of cervical cancer, the third most common cancer among women globally and the second most frequent in Mexico. Persistent infection with high-risk HPV genotypes is associated with premalignant lesions and cervical cancer development. HPVs considered as low risk or not yet classified, are often found in coinfection with different HPV genotypes. Indeed, HPV62 is one of the most prevalent HPV detected in some countries, but there is limited information about its prevalence in other regions and there are no HPV62 variants currently described. The aim of this study was to determine the prevalence of HPV62 in cervical samples from Mexican women and to identify mutations in the L1, E6 and E7 genes, which have never been reported in our population. METHODS: HPV screening was performed by Cobas HPV Test in women who attended prevention health programs and dysplasia clinics. All HPV positive samples (n = 491) and 87 additional cervical cancer samples were then genotyped with Linear Array HPV Genotyping test. Some samples were selected to corroborate genotyping by Next-Generation sequencing. On the other hand, nucleotide changes in L1, E6 and E7 genes were determined using PCR, Sanger sequencing and analysis with the CLC-MainWorkbench 7.6.1 software. L1 protein structure was predicted with the I-TASSER server. RESULTS: Using Linear Array, HPV62 prevalence was 7.6% in general population, 8% in Cervical Intraepithelial Neoplasia grade 1 (CIN1) samples and 4.6% in cervical samples. The presence of HPV62 was confirmed with Next-Generation sequencing. Regarding L1 gene, novel sequence variations were detected, but they did not alter the tertiary structure of the protein. Moreover, several nucleotide substitutions were found in E6 and E7 genes compared to reference HPV62 genomic sequence. Specifically, three non-synonymous sequence variations were detected, two in E6 and one in E7. CONCLUSIONS: HPV62 is a frequent HPV genotype found mainly in general population and in women with CIN1, and in 90.5% of the cases it was found in coinfection with other HPVs. Novel nucleotide changes in its L1, E6 and E7 genes were detected, some of them lead to changes in the protein sequence.