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1.
Cancer Res ; 80(18): 3803-3809, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32631904

RESUMO

Human papillomavirus (HPV) 16 displays substantial sequence variation; four HPV16 lineages (A, B, C, and D) have been described as well as multiple sublineages. To identify molecular events associated with HPV16 carcinogenesis, we evaluated viral variation, the integration of HPV16, and somatic mutation in 96 cervical cancer samples from Guatemala. A total of 65% (62/96) of the samples had integrated HPV16 sequences and integration was associated with an earlier age of diagnosis and premenopausal disease. HPV16 integration sites were broadly distributed in the genome, but in one tumor, HPV16 integrated into the promoter of the IFN regulatory factor 4 (IRF4) gene, which plays an important role in the regulation of the IFN response to viral infection. The HPV16 D2 and D3 sublineages were found in 23% and 30% of the tumors, respectively, and were significantly associated with adenocarcinoma. D2-positive tumors had a higher rate of integration, earlier age of diagnosis, and a lower rate of somatic mutation, whereas D3-positive tumors were less likely to integrate, had later age of diagnosis, and exhibited a higher rate of somatic mutation. In conclusion, Guatemalan cervical tumors have a high frequency of very high-risk HPV16 D2 and D3 sublineages harboring distinct histology, which may help guide future therapeutic strategies to target the tumor and reduce recurrence. SIGNIFICANCE: This study details the biological and molecular properties of the most pathogenic forms of HPV16, the cause of the majority of cervical cancers.

2.
Health Sci Rep ; 3(2): e155, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32382660

RESUMO

Background and aims: Guatemala has the highest incidence of hepatocellular carcinoma (HCC) in the Western hemisphere. The major risk factors in Guatemala are not well characterized, but the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) appears to be low, while the prevalence of aflatoxin (AFB1) exposure appears to be high. To examine whether AFB1 may contribute to the elevated incidence of HCC in Guatemala, this study examined the frequency of the AFB1-signature mutation in the TP53 gene (R249S) as well as other somatic mutations. In addition, we assessed whether the frequency of the TP53 mutation differed by sex. Methods: Formalin-fixed, paraffin-embedded (FFPE) HCC tissues were obtained from three hospitals in Guatemala City between 2016 and 2017. In addition, tumor tissues preserved in RNAlater were also obtained. Sociodemographic and clinical information including HBV and HCV status were collected. Targeted sequencing of TP53 was performed in the FFPE samples, and a panel of 253 cancer-related genes was sequenced in the RNAlater samples. Results: Ninety-one FFPE tissues were examined, from 52 men and 39 women. Median (IQR) age at diagnosis was 62 (51-70). Among those with known HBV and HCV status, two were HBV+ and three were HCV+. Overall, 47% of the HCCs had a TP53 mutation. The AFB1-signature R249S mutation was present in 24%. No overlap between the R249S mutation and HBV+ was observed in this cohort. Among 18 RNAlater samples examined, 44% had any TP53 mutation and 33% had the R249S mutation. Other somatic mutations were identified in known HCC driver genes. Conclusions: The presence of the TP53 R249S mutation in the samples studied suggests that AFB1 may contribute to the high incidence of HCC in Guatemala. The proportion of HBV+ tumors was low, suggesting that AFB1 may be associated with HCC in the absence of concomitant HBV infection. Further investigation of AFB1 and other risk factors for HCC in Guatemala is warranted.

3.
JCO Glob Oncol ; 6: 617-627, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32302236

RESUMO

PURPOSE: Cervical cancer screening is not well implemented in many low- and middle-income countries (LMICs). Mobile health (mHealth) refers to utilization of mobile technologies in health promotion and disease management. We aimed to qualitatively synthesize published articles reporting the impact of mHealth on cervical cancer screening-related health behaviors. METHODS: Three reviewers independently reviewed articles with the following criteria: the exposure or intervention of interest was mHealth, including messages or educational information sent via mobile telephone or e-mail; the comparison was people not using mHealth technology to receive screening-related information, and studies comparing multiple different mHealth interventional strategies were also eligible; the primary outcome was cervical cancer screening uptake, and secondary outcomes included awareness, intention, and knowledge of screening; appropriate research designs included randomized controlled trials and quasi-experimental or observational research; and the study was conducted in an LMIC. RESULTS: Of the 8 selected studies, 5 treated mobile telephone or message reminders as the exposure or intervention, and 3 compared the effects of different messages on screening uptake. The outcomes were diverse, including screening uptake (n = 4); health beliefs regarding the Papanicolaou (Pap) test (n = 1); knowledge of, attitude toward, and adherence to colpocytologic examination (n = 1); interest in receiving messages about Pap test results or appointment (n = 1); and return for Pap test reports (n = 1). CONCLUSION: Overall, our systematic review suggests that mobile technologies, particularly telephone reminders or messages, lead to increased Pap test uptake; additional work is needed to unequivocally verify whether mhealth interventions can improve knowledge regarding cervical cancer. Our study will inform mHealth-based interventions for cervical cancer screening promotion in LMICs.

5.
J Glob Oncol ; 5: 1-5, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31067142

RESUMO

PURPOSE: Despite being the only hospital to provide comprehensive cervical cancer treatment to many medically underserved Guatemalan women, no assessment of the cervical cancer patient population at the Guatemala Cancer Institute has been performed. To understand the demographics of the patient population, their treatment outcomes, and access to care, we sought to assess treatment compliance of patients with cervical cancer at the Guatemala Cancer Institute and its effects on patient outcomes. METHODS: A retrospective chart review was conducted of patients with cervical cancer between 2005 and 2007 and assessed for follow-up through December 2015. Demographics and clinical characteristics were tabulated. A Kaplan-Meier curve to model compliance was generated. RESULTS: Ninety-two patients with invasive cancer were analyzed. Most presented with squamous cell carcinoma (73%) and at locally advanced stages (IIB, 51%; IIIB, 33%). Most (75 of 92, 81.5%) initiated treatment after diagnosis, but 18.5% (17 of 92) were lost to follow-up before treatment initiation. For treatment, 97% received external beam radiation, 84% brachytherapy, and 4% concomitant chemotherapy. Nearly 20% of patients were lost to follow-up in the first 6 months and 65% in the first 5 years. Of the 67 patients who completed treatment, only 15 (16% of the initial cohort) were diagnosed with a recurrence. No deaths were recorded. CONCLUSION: The low recurrence rate and no documented deaths suggest a correlation with the low compliance rate and poor follow-up. This finding highlights the need to examine more fully the barriers to compliance and access to care among this population to optimize the treatment of cervical cancer.


Assuntos
Cooperação do Paciente/psicologia , Neoplasias do Colo do Útero/psicologia , Neoplasias do Colo do Útero/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/psicologia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Feminino , Guatemala/epidemiologia , Humanos , Perda de Seguimento , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/psicologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Adulto Jovem
7.
J Glob Oncol ; 4: 1-11, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30241165

RESUMO

The Central America Four (CA-4) region, comprising Guatemala, Honduras, El Salvador, and Nicaragua, is the largest low- and middle-income country region in the Western Hemisphere, with over 36 million inhabitants. The CA-4 nations share a common geography, history, language, and development indices, and unified with open borders in 2006. The growing CA-4 cancer burden among the noncommunicable diseases is expected to increase 73% by 2030, which argues for a regional approach to cancer control. This has driven efforts to establish population-based cancer registries as a central component of the cancer control plans. The involvement of international and academic partners in an array of initiatives to improve cancer information and control in the CA-4 has accelerated over the past several years. Existing data underscore that the infectious cancers (cervical, stomach, and liver) are a particular burden. All four countries have committed to establishing regional population-based cancer registries and have advanced significantly in pediatric cancer registration. The challenges common to each nation include the lack of national cancer control plans and departments, competing health priorities, lack of trained personnel, and sustainability strategies. General recommendations to address these challenges are outlined. The ongoing regional, international, and academic cooperation has proven helpful and is expected to continue to be a powerful instrument to contribute to the design and implementation of long-term national cancer control plans.


Assuntos
Confiabilidade dos Dados , Neoplasias/epidemiologia , América Central/epidemiologia , Efeitos Psicossociais da Doença , Demografia , Humanos , Incidência , Mortalidade , Neoplasias/prevenção & controle , Neoplasias/terapia , Prática Associada , Vigilância em Saúde Pública , Sistema de Registros
8.
BMC Cancer ; 18(1): 562, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29764400

RESUMO

BACKGROUND: A low cost and accurate method for detecting high-risk (HR) human papillomavirus (HPV) is important to permit HPV testing for cervical cancer prevention. We used a commercially available HPV method (H13, Hybribio) which was documented to function accurately in a reduced volume of cervical specimen to determine the most prevalent HPV types and the distribution of HPV infections in over 1795 cancer-free women in Guatemala undergoing primary screening for cervical cancer by cytology. METHODS: HR-HPV detection was attempted in cervical samples from 1795 cancer-free women receiving Pap smears using the Hybribio™ real-time PCR assay of 13 HR types. The test includes a globin gene internal control. HPV positive samples were sequenced to determine viral type. Age-specific prevalence of HPV was also assessed in the study population. RESULTS: A total of 13% (226/1717) of women tested HPV+, with 78 samples (4.3%) failing to amplify the internal control. The highest prevalence was found in younger women (< 30 years, 22%) and older ones (≥60 years, 15%). The six most common HR-HPV types among the 148 HPV+ typed were HPV16 (22%), HPV18 (11%), HPV39 (11%), HPV58 (10%), HPV52 (8%), and HPV45 (8%). CONCLUSIONS: In this sample of cancer free women in Guatemala, HPV16 was the most prevalent HR type in Guatemala and the age-specific prevalence curve peaked in younger ages. Women in the 30-59-year age groups had a prevalence of HR-HPV of 8%, however, larger studies to better describe the epidemiology of HPV in Guatemala are needed.


Assuntos
Infecções Assintomáticas/epidemiologia , Detecção Precoce de Câncer/economia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Fatores Etários , Idoso , Neoplasia Intraepitelial Cervical , Colo do Útero/virologia , Detecção Precoce de Câncer/métodos , Feminino , Genótipo , Guatemala/epidemiologia , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Prevalência , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Adulto Jovem
9.
J Ethnobiol Ethnomed ; 13(1): 44, 2017 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-28789670

RESUMO

BACKGROUND: Up to one half of the population in Africa, Asia and Latin America has little access to high-quality biomedical services and relies on traditional health systems. Medical pluralism is thus in many developing countries the rule rather than the exception, which is why the World Health Organization is calling for intercultural partnerships to improve health care in these regions. They are, however, challenging due to disparate knowledge systems and lack of trust that hamper understanding and collaboration. We developed a collaborative, patient-centered boundary mechanism to overcome these challenges and to foster intercultural partnerships in health care. To assess its impact on the quality of intercultural patient care in a medically pluralistic developing country, we conducted and evaluated a case study. METHODS: The case study took place in Guatemala, since previous efforts to initiate intercultural medical partnerships in this country were hampered by intense historical and societal conflicts. It was designed by a team from ETH Zurich's Transdisciplinarity Lab, the National Cancer Institute of Guatemala, two traditional Councils of Elders and 25 Mayan healers from the Kaqchikel and Q'eqchi' linguistic groups. It was implemented from January 2014 to July 2015. Scientists and traditional political authorities collaborated to facilitate workshops, comparative diagnoses and patient referrals, which were conducted jointly by biomedical and traditional practitioners. The traditional medical practices were thoroughly documented, as were the health-seeking pathways of patients, and the overall impact was evaluated. RESULTS: The boundary mechanism was successful in discerning barriers of access for indigenous patients in the biomedical health system, and in building trust between doctors and healers. Learning outcomes included a reduction of stereotypical attitudes towards traditional healers, improved biomedical procedures due to enhanced self-reflection of doctors, and improved traditional health care due to refined diagnoses and adapted treatment strategies. In individual cases, the beneficial effects of traditional treatments were remarkable, and the doctors continued to collaborate with healers after the study was completed. Comparison of the two linguistic groups illustrated that the outcomes are highly context-dependent. CONCLUSIONS: If well adapted to local context, patient-centered boundary mechanisms can enable intercultural partnerships by creating access, building trust and fostering mutual learning, even in circumstances as complex as those in Guatemala. Creating multilateral patient-centered boundary mechanisms is thus a promising approach to improve health care in medically pluralistic developing countries.


Assuntos
Diversidade Cultural , Assistência à Saúde/organização & administração , Medicina Tradicional , Assistência Centrada no Paciente/métodos , Cultura , Assistência à Saúde/métodos , Guatemala , Humanos , Índios Centro-Americanos/etnologia , Medicina Tradicional/métodos , Assistência Centrada no Paciente/organização & administração
10.
J Glob Oncol ; 2(2): 56-67, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28717684

RESUMO

PURPOSE: Cultural diversity in clinical encounters is common, yet mental constructions regarding cancer that influence expected treatment are poorly studied for indigenous people. We explored Maya healers' conceptions, diagnosis, and treatment of cancer to remedy this problem. METHODS: In-depth structured interviews with 67 traditional Maya healers in Guatemala across Kaqchikel, Kiche', Mam, Mopan, and Q'eqchi' ethnolinguistic groups were conducted by using a transdisciplinary format. Analysis of qualitative data in categorized matrixes allowed for statistical examination of tendencies and the results were complemented by validation workshops with Maya representatives. RESULTS: Maya classification of diseases has broad categories of malignant diseases including cancer. Specific Maya terms might equate to particular cancer types, which would open new avenues for research. Notions of malignancy and metastasis were expressed by healers as core characteristics of cancer, a disease believed to be both material and spiritual. Resolution of and/or treatment for cancer is based on restoring physical, mental, emotional, and spiritual equilibrium of the patient and extending that equilibrium to his larger social circle. CONCLUSION: Maya conceptions of cancer determine how traditional diagnostic tools are used and dictate treatment options that include the patient's social-spiritual support system. Official health care providers' understanding of these principles can improve implementation of culturally appropriate protocols that increase indigenous patients' compliance and reduce rates of treatment abandonment.

11.
Clin Cancer Res ; 21(23): 5360-70, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26080840

RESUMO

PURPOSE: Cervical cancer is one of the most common causes of cancer mortality for women living in poverty, causing more than 28,000 deaths annually in Latin America and 266,000 worldwide. To better understand the molecular basis of the disease, we ascertained blood and tumor samples from Guatemala and Venezuela and performed genomic characterization. EXPERIMENTAL DESIGN: We performed human papillomavirus (HPV) typing and identified somatically mutated genes using exome and ultra-deep targeted sequencing with confirmation in samples from Mexico. Copy number changes were also assessed in the exome sequence. RESULTS: Cervical cancer cases in Guatemala and Venezuela have an average age of diagnosis of 50 years and 5.6 children. Analysis of 675 tumors revealed activation of PIK3CA and other PI3K/AKT pathway genes in 31% of squamous carcinomas and 24% of adeno- and adenosquamous tumors, predominantly at two sites (E542K, E545K) in the helical domain of the PIK3CA gene. This distribution of PIK3CA mutations is distinct from most other cancer types and does not result in the in vitro phosphorylation of AKT. Somatic mutations were more frequent in squamous carcinomas diagnosed after the age of 50 years. Frequent gain of chromosome 3q was found, and low PIK3CA mutation fractions in many tumors suggest that PI3K mutation can be a late event in tumor progression. CONCLUSIONS: PI3K pathway mutation is important to cervical carcinogenesis in Latin America. Therapeutic agents that directly target PI3K could play a role in the therapy of this common malignancy.


Assuntos
Genoma Humano , Genômica , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/etiologia , Adulto , Idoso , Alphapapillomavirus/classificação , Alphapapillomavirus/genética , Biomarcadores Tumorais , Mapeamento Cromossômico , Classe I de Fosfatidilinositol 3-Quinases , Variações do Número de Cópias de DNA , Exoma , Feminino , Expressão Gênica , Guatemala/epidemiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Risco , Transdução de Sinais , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Venezuela/epidemiologia
12.
Bull World Health Organ ; 92(4): 297-302, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24700998

RESUMO

PROBLEM: Guatemala is experiencing an increasing burden of cancer but lacks capacity for cancer prevention, control and research. APPROACH: In partnership with a medical school in the United States of America, a multidisciplinary Cancer Control Research Training Institute was developed at the Instituto de Cancerología (INCAN) in Guatemala City. This institute provided a year-long training programme for clinicians that focused on research methods in population health and sociocultural anthropology. The programme included didactic experiences in Guatemala and the United States as well as applied training in which participants developed research protocols responsive to Guatemala's cancer needs. LOCAL SETTING: Although INCAN is the point of referral and service for Guatemala's cancer patients, the institute's administration is also interested in increasing cancer research - with a focus on population health. INCAN is thus a resource for capacity building within the context of cancer prevention and control. RELEVANT CHANGES: Trainees increased their self-efficacy for the design and conduct of research. Value-added benefits included establishment of an annual cancer seminar and workshops in cancer pathology and qualitative analysis. INCAN has recently incorporated some of the programme's components into its residency training and established a research department. LESSONS LEARNT: A training programme for clinicians can build cancer research capacity in low- and middle-income countries. Training in population-based research methods will enable countries such as Guatemala to gather country-specific data. Once collected, such data can be used to assess the burden of cancer-related disease, guide policy for reducing it and identify priority areas for cancer prevention and treatment.


Assuntos
Educação Médica/métodos , Neoplasias , Pesquisa/educação , Fortalecimento Institucional , Currículo , Países em Desenvolvimento , Guatemala , Humanos , Cooperação Internacional , Estados Unidos
13.
Rev. guatemalteca cir ; 9(1): 20-5, ene.-abr. 2000. ilus
Artigo em Espanhol | LILACS | ID: lil-278668

RESUMO

Los tumores endocrinos del páncreas son, afortunadamente, neoplasias muy poco frecuentes. Los insulinomas espeficíficamente, son tumores que se originan en las células Beta de los islotes de Langerhans y causan hiperinsulenemia e hipoglucemia. Se presenta el caso de un paciente masculino de 43 años de edad, conuna historia relativamente laarga (17 meses) de mareos y desmayos matutinos, que inicialmente fue mal diagnosticado, sobre todo, por no sospechar la presencia de este tipo de patología. Al hacerlo, se indicaron además de los estudios específicos de laboratorio,varios estudios por imágenes que no fueron concluyentes, pero se decidió intervenir quirúrgicamente al paciente con el hallazgo de 2 tumores pancreaticos que, anatomopatológicamente, fueron documentados como insulinomas. La evolución postoperatoria del paciente fue satisfactoria


Assuntos
Humanos , Masculino , Adulto , Hipoglicemia , Insulinoma , Neoplasias Pancreáticas/diagnóstico
14.
Rev. guatemalteca cir ; 8(2): 66-9, abr.-ago. 1999. tab
Artigo em Espanhol | LILACS | ID: lil-262846

RESUMO

Con el propósito de demostrar la utilidad de la infiltración local de metronidazole en la prevención de heridas operatorias de apendicectomía, se realizó un estudio prospectivo de pacientes con apendicitis aguda, que fueron operados en dos hospitales del Instituto Guatemalteco de Seguridad Social entre los meses de marzo a agosto de 1993. Se encontró una diferencia estadísticamente significativa en la incidencia de infección de herida operatoria entre el grupo control (11 pacientes para un 22 y el grupo experimental, con infiltración preoperatoria de metronidazole en el sitio de la incisión (2 pacientes para un 4.34). Se concluyó que este tipo de práctica podría utilizarse como rutina para disminuir la incidencia de infección de herida operatoria en apendicitis aguda


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Apendicectomia , Apendicite/tratamento farmacológico , Infecções por Escherichia coli , Infecção da Ferida Cirúrgica/prevenção & controle , Metronidazol/uso terapêutico , Infecções Estafilocócicas
15.
Rev. guatemalteca cir ; 8(1): 12-6, ene.-abr. 1999. tab
Artigo em Espanhol | LILACS | ID: lil-262883

RESUMO

Se realizó un estudio retrospectivo para evaluar la utilización y resultados de la quimio y radioterapia en los pacientes con cáncer del colon y recto según estudio de Dukes entre agosto de 1987 a diciembre de 1996, en el Hospital General de Enfermedad Común del Instituto Guatemalteco de Seguridad Social. Se encontró que para los estadios Dukes A, la cirugía es prácticamente curativa y para el estadio Dukes B hay una respuesta favorable con el uso de quimioterapia. Para los pacientes con estadios Dukes C, que fueron la mayoría, se observó los mejores resultados con esquemas que involucren alguna terapia tanto pre como postoperatoria


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Estadiamento de Neoplasias/classificação , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgia
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