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1.
Transl Oncol ; 14(12): 101229, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34592589

RESUMO

Tumour metastasis accounts for over 90% of cancer related deaths. The platelet is a key blood component, which facilitates efficient metastasis. This study aimed to understand the molecular mechanisms involved in tumour-platelet cell interactions. The interaction between cancer cells and platelets was examined in 15 epithelial cell lines, representing 7 cancer types. Gene expression analysis of EMT-associated and cancer stemness genes was performed by RT-PCR. Whole transcriptome analysis (WTA) was performed using Affymetrix 2.0ST arrays on a platelet co-cultured ovarian model. Platelet adhesion and activation occurred across all tumour types. WTA identified increases in cellular movement, migration, invasion, adhesion, development, differentiation and inflammation genes and decreases in processes associated with cell death and survival following platelet interaction. Increased invasive capacity was also observed in a subset of cell lines. A cross-comparison with a platelet co-cultured mouse model identified 5 common altered genes; PAI-1, PLEK2, CD73, TNC, and SDPR. Platelet cancer cell interactions are a key factor in driving the pro-metastatic phenotype and appear to be mediated by 5 key genes which have established roles in metastasis. Targeting these metastasis mediators could improve cancer patient outcomes.

2.
Health Expect ; 24(6): 2023-2035, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34476875

RESUMO

BACKGROUND: Effective screening can prevent cervical cancer, but many women choose not to attend their screening tests. OBJECTIVE: This study aimed to investigate behavioural influences on cervical screening participation using the Theoretical Domains Framework (TDF) and COM-B models of behaviour change. DESIGN: A qualitative study and semistructured phone interviews were conducted with women invited for routine screening tests within the national cervical screening programme in Ireland. SETTING AND PARTICIPANTS: Forty-eight women aged 25-65 years were recruited from the national screening register. RESULTS: Seven core themes were identified that mapped to three COM-B components and 11 TDF domains: (1) knowledge of cervical cancer and screening, (2) coping with smear tests, (3) competing motivational processes-automatic and reflective, (4) cognitive resources, (5) role of social support, (6) environmental influences and (7) perceputal and practical influences. A range of knowledge about screening, perceived risk of cervical cancer and human papillomavirus infection was evident. Factors that influenced screening behaviours may be hierarchical-some were assigned greater importance than others. Positive screening behaviours were linked to autonomous motivation. Deficits in physical and psychological capability (inadequate coping skills) were barriers to screening, while physical and social opportunity (e.g. healthcare professional 'champions') could facilitate participation. Older women raised age-related issues (e.g. screening no longer necessary) and had more negative attitudes to screening, while younger women identified practical barriers. CONCLUSIONS: This study provides insight into screening participation and will aid development of theoretically informed interventions to increase uptake. PATIENT OR PUBLIC CONTRIBUTION: Women invited for screening tests through the national screening programme were interviewed. A Public & Patient Involvement (PPI) Panel, established to provide input into all CERVIVA research projects, advised the research team on recruitment materials and were given the opportunity to review and comment on the interview topic guide. This panel is made up of six women with various cervical screening histories and experiences.

3.
HRB Open Res ; 4: 44, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34458677

RESUMO

Background:  Cervical screening uptake is declining in several countries. Primary care practitioners could play a greater role in maximising uptake, but better understanding is needed of practitioners' cervical screening-related behaviours. Among general practitioners (GPs) and practice nurses, we aimed to identify cervical screening-related clinical behaviours; clarify practitioners' roles/responsibilities; and determine factors likely to influence clinical behaviours. Methods: Telephone interviews were conducted with GPs and practice nurses in Ireland. Interview transcripts were analysed using the Theoretical Domains Framework (TDF), a comprehensive psychological framework of factors influencing clinical behaviour. Results: 14 GPs and 19 practice nurses participated. Key clinical behaviours identified were offering smears and encouraging women to attend for smears. Smeartaking responsibility was considered a predominantly female role. Of 12 possible theoretical domains, 11 were identified in relation to these behaviours. Those judged to be the most important were beliefs about capabilities; environmental context and resources; social influences; and behavioural regulation. Difficulties in obtaining smears from certain subgroups of women and inexperience of some GPs in smeartaking arose in relation to beliefs about capabilities. The need for public health education and reluctance of male practitioners to discuss cervical screening with female patients emerged in relation to social influences.   Conclusions: We identified - for the first time - primary care practitioners' cervical-screening related clinical behaviours, their perceived roles and responsibilities, and factors likely to influence behaviours. The results could inform initiatives to enable practitioners to encourage women to have smear tests which in turn, may help increase cervical screening uptake.

4.
PLoS Comput Biol ; 17(8): e1009289, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34415913

RESUMO

The epidemic increase in the incidence of Human Papilloma Virus (HPV) related Oropharyngeal Squamous Cell Carcinomas (OPSCCs) in several countries worldwide represents a significant public health concern. Although gender neutral HPV vaccination programmes are expected to cause a reduction in the incidence rates of OPSCCs, these effects will not be evident in the foreseeable future. Secondary prevention strategies are currently not feasible due to an incomplete understanding of the natural history of oral HPV infections in OPSCCs. The key parameters that govern natural history models remain largely ill-defined for HPV related OPSCCs and cannot be easily inferred from experimental data. Mathematical models have been used to estimate some of these ill-defined parameters in cervical cancer, another HPV related cancer leading to successful implementation of cancer prevention strategies. We outline a "double-Bayesian" mathematical modelling approach, whereby, a Bayesian machine learning model first estimates the probability of an individual having an oral HPV infection, given OPSCC and other covariate information. The model is then inverted using Bayes' theorem to reverse the probability relationship. We use data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry, SEER Head and Neck with HPV Database and the National Health and Nutrition Examination Surveys (NHANES), representing the adult population in the United States to derive our model. The model contains 8,106 OPSCC patients of which 73.0% had an oral HPV infection. When stratified by age, sex, marital status and race/ethnicity, the model estimated a higher conditional probability for developing OPSCCs given an oral HPV infection in non-Hispanic White males and females compared to other races/ethnicities. The proposed Bayesian model represents a proof-of-concept of a natural history model of HPV driven OPSCCs and outlines a strategy for estimating the conditional probability of an individual's risk of developing OPSCC following an oral HPV infection.


Assuntos
Alphapapillomavirus/patogenicidade , Teorema de Bayes , Aprendizado de Máquina , Neoplasias Orofaríngeas/virologia , Probabilidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/epidemiologia , Programa de SEER , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia
5.
Physiother Theory Pract ; : 1-10, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34167435

RESUMO

BACKGROUND: An estimated 45% of concussions are reported to be related to motor vehicle collisions (MVC). However, limited research exists involving the treatment of MVC-related concussion, especially when combined with whiplash-associated disorders (WAD). Purpose: The purpose of this case series is to examine the patient response to an irritability-based approach to the physiological, cervical, and vestibulo-ocular trajectories in patients with diagnosed concussion and WAD disorder following an MVC. Case Description: Three patients clinically diagnosed by a neurologist with WAD and concussion following a rear-end MVC were evaluated and treated in an outpatient physical therapy setting. Each individual was progressed through an irritability-based treatment approach based on individual symptom presentation. Outcomes: Following therapy, 2 of 3 patients reported full resolution of subjective symptoms with a negative Vestibular Oculo-motor Screening All patients exceeded their predicted goals based on Focus on Therapeutic Outcomes score. CONCLUSION: This case series demonstrated successful treatment of all three individuals with concussion and concurrent WAD. Two of three individuals demonstrated full resolution of subjective symptoms and objective impairments at the end of treatment. Further research is warranted into the effectiveness of a multi-factorial approach to address the highly variable symptom profile of individuals with concussion and WAD.

6.
Nat Protoc ; 16(7): 3716-3735, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34117476

RESUMO

Raman spectroscopy can provide a rapid, label-free, nondestructive measurement of the chemical fingerprint of a sample and has shown potential for cancer screening and diagnosis. Here we report a protocol for Raman microspectroscopic analysis of different exfoliative cytology samples (cervical, oral and lung), covering sample preparation, spectral acquisition, preprocessing and data analysis. The protocol takes 2 h 20 min for sample preparation, measurement and data preprocessing and up to 8 h for a complete analysis. A key feature of the protocol is that it uses the same sample preparation procedure as commonly used in diagnostic cytology laboratories (i.e., liquid-based cytology on glass slides), ensuring compatibility with clinical workflows. Our protocol also covers methods to correct for the spectral contribution of glass and sample pretreatment methods to remove contaminants (such as blood and mucus) that can obscure spectral features in the exfoliated cells and lead to variability. The protocol establishes a standardized clinical routine allowing the collection of highly reproducible data for Raman spectral cytopathology for cancer diagnostic applications for cervical and lung cancer and for monitoring suspicious lesions for oral cancer.


Assuntos
Detecção Precoce de Câncer , Neoplasias/diagnóstico , Neoplasias/patologia , Análise Espectral Raman/métodos , Algoritmos , Colo do Útero/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Pulmão/patologia
7.
Mol Cancer ; 20(1): 59, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789677

RESUMO

Cancer cells that transit from primary tumours into the circulatory system are known as circulating tumour cells (CTCs). These cancer cells have unique phenotypic and genotypic characteristics which allow them to survive within the circulation, subsequently extravasate and metastasise. CTCs have emerged as a useful diagnostic tool using "liquid biopsies" to report on the metastatic potential of cancers. However, CTCs by their nature interact with components of the blood circulatory system on a constant basis, influencing both their physical and morphological characteristics as well as metastatic capabilities. These properties and the associated molecular profile may provide critical diagnostic and prognostic capabilities in the clinic. Platelets interact with CTCs within minutes of their dissemination and are crucial in the formation of the initial metastatic niche. Platelets and coagulation proteins also alter the fate of a CTC by influencing EMT, promoting pro-survival signalling and aiding in evading immune cell destruction. CTCs have the capacity to directly hijack immune cells and utilise them to aid in CTC metastatic seeding processes. The disruption of CTC clusters may also offer a strategy for the treatment of advance staged cancers. Therapeutic disruption of these heterotypical interactions as well as direct CTC targeting hold great promise, especially with the advent of new immunotherapies and personalised medicines. Understanding the molecular role that platelets, immune cells and the coagulation cascade play in CTC biology will allow us to identify and characterise the most clinically relevant CTCs from patients. This will subsequently advance the clinical utility of CTCs in cancer diagnosis/prognosis.


Assuntos
Coagulação Sanguínea , Plaquetas/metabolismo , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Animais , Biomarcadores , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Comunicação Celular/genética , Comunicação Celular/imunologia , Gerenciamento Clínico , Suscetibilidade a Doenças , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/imunologia , Humanos , Neoplasias/sangue , Neoplasias/complicações , Neoplasias/etiologia , Neoplasias/patologia
8.
Cancers (Basel) ; 13(9)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33921939

RESUMO

The role of persistent high-risk human papillomavirus (HPV) infection in the development of cervical precancer and cancer is now well accepted, and HPV testing has recently been introduced for primary cervical screening. However, the low specificity of HPV DNA testing can result in large numbers of women with an HPV-positive result, and additional triage approaches are needed to avoid over-referral to colposcopy and overtreatment. The aim of this study was to assess Raman spectroscopy as a potential triage test to discriminate between transient and persistent HPV infection. HPV DNA status and mRNA status were confirmed in ThinPrep® cervical samples (n = 60) using the Cobas 4800 and APTIMA HPV test, respectively. Raman spectra were recorded from single-cell nuclei and subjected to partial least squares discriminant analysis (PLSDA). In addition, the PLSDA classification model was validated using a blinded independent test set (n = 14). Sensitivity of 85% and specificity of 92% were achieved for the classification of transient and persistent HPV infection, and this increased to 90% sensitivity and 100% specificity when mean sample spectra were used instead of individual cellular spectra. This study showed that Raman spectroscopy has potential as a triage test for HPV-positive women to identify persistent HPV infection.

9.
J Oral Pathol Med ; 50(7): 692-699, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33733523

RESUMO

BACKGROUND: Considering the shared aetiology of Human Papillomavirus infections in oropharyngeal and cervical cancers and the possible role for sexual transmission, several key aspects of the relationship between cervical and oral infections merit investigation, including prevalence of concomitant oral HPV infection and type-specific concordance with concurrent cervical infections. METHODS: A cross-section study was performed on women referred to colposcopy clinics with cytological abnormalities and a cervical HPV infection. An oral rinse sample was taken from the participants at their baseline visit for HPV testing, and a demographic and risk factor questionnaire was also administered. HPV DNA testing was carried out on the Cobas 4800 platform and extended genotyping was carried out with the INNO-LiPA HPV Genotyping Extra II assay. HPV genotyping was also carried out on the concurrent cervical tissue samples on all women who had a positive oral HPV infection. RESULTS: The prevalence of oral HPV infections was 10.0% (95%CI:5.9-13.7) in the study population. HPV18 was the most frequent genotype (7.0%). Concordant oral and cervical HPV infections were detected in 28.6% of women. Age (p = 0.005) and level of education (p = 0.02) were significantly associated with a prevalent oral HPV infection. CONCLUSION: Concomitant oral HPV infections were present in 10.0% of women referred to colposcopy with a pre-existing cervical HPV infections and cytological abnormalities. Although mild type-specific concordance was observed between oral and cervical HPV infections, findings suggest that infections at these sites may not be independent of each other.


Assuntos
Neoplasia Intraepitelial Cervical , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Colposcopia , Feminino , Genótipo , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Gravidez , Prevalência
10.
PLoS One ; 15(12): e0243715, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33370338

RESUMO

Despite the use of front-line anticancer drugs such as paclitaxel for ovarian cancer treatment, mortality rates have remained almost unchanged for the past three decades and the majority of patients will develop recurrent chemoresistant disease which remains largely untreatable. Overcoming chemoresistance or preventing its onset in the first instance remains one of the major challenges for ovarian cancer research. In this study, we demonstrate a key link between senescence and inflammation and how this complex network involving the biomarkers MAD2, TLR4 and MyD88 drives paclitaxel resistance in ovarian cancer. This was investigated using siRNA knockdown of MAD2, TLR4 and MyD88 in two ovarian cancer cell lines, A2780 and SKOV-3 cells and overexpression of MyD88 in A2780 cells. Interestingly, siRNA knockdown of MAD2 led to a significant increase in TLR4 gene expression, this was coupled with the development of a highly paclitaxel-resistant cell phenotype. Additionally, siRNA knockdown of MAD2 or TLR4 in the serous ovarian cell model OVCAR-3 resulted in a significant increase in TLR4 or MAD2 expression respectively. Microarray analysis of SKOV-3 cells following knockdown of TLR4 or MAD2 highlighted a number of significantly altered biological processes including EMT, complement, coagulation, proliferation and survival, ECM remodelling, olfactory receptor signalling, ErbB signalling, DNA packaging, Insulin-like growth factor signalling, ion transport and alteration of components of the cytoskeleton. Cross comparison of the microarray data sets identified 7 overlapping genes including MMP13, ACTBL2, AMTN, PLXDC2, LYZL1, CCBE1 and CKS2. These results demonstrate an important link between these biomarkers, which to our knowledge has never before been shown in ovarian cancer. In the future, we hope that triaging patients into alterative treatment groups based on the expression of these three biomarkers or therapeutic targeting of the mechanisms they are involved in will lead to improvements in patient outcome and prevent the development of chemoresistance.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Senescência Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Proteínas Mad2/genética , Fator 88 de Diferenciação Mieloide/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Paclitaxel/uso terapêutico , RNA Interferente Pequeno/metabolismo , Receptor 4 Toll-Like/genética
11.
Proc Natl Acad Sci U S A ; 117(40): 24964-24973, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32958663

RESUMO

Influenza A virus (IAV) infection during pregnancy causes severe maternal and perinatal complications, despite a lack of vertical transmission of IAV across the placenta. Here, we demonstrate a significant alteration in the maternal vascular landscape that underpins the maternal and downstream fetal pathology to IAV infection in mice. In IAV infection of nonpregnant mice, the local lung inflammatory response was contained to the lungs and was self-resolving, whereas in pregnant mice, virus dissemination to major maternal blood vessels, including the aorta, resulted in a peripheral "vascular storm," with elevated proinflammatory and antiviral mediators and the influx of Ly6Clow and Ly6Chigh monocytes, plus neutrophils and T cells. This vascular storm was associated with elevated levels of the adhesion molecules ICAM and VCAM and the pattern-recognition receptors TLR7 and TLR9 in the vascular wall, resulting in profound vascular dysfunction. The sequalae of this IAV-driven vascular storm included placental growth retardation and intrauterine growth restriction, evidence of placental and fetal brain hypoxia, and increased circulating cell free fetal DNA and soluble Flt1. In contrast, IAV infection in nonpregnant mice caused no obvious alterations in endothelial function or vascular inflammation. Therefore, IAV infection during pregnancy drives a significant systemic vascular alteration in pregnant dams, which likely suppresses critical blood flow to the placenta and fetus. This study in mice provides a fundamental mechanistic insight and a paradigm into how an immune response to a respiratory virus, such as IAV, is likely to specifically drive maternal and fetal pathologies during pregnancy.


Assuntos
Imunidade Adaptativa/genética , Imunidade Inata/genética , Inflamação/genética , Vírus da Influenza A/genética , Animais , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Feminino , Feto/imunologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Inflamação/virologia , Vírus da Influenza A/patogenicidade , Influenza Humana/genética , Influenza Humana/imunologia , Influenza Humana/virologia , Glicoproteínas de Membrana/genética , Camundongos , Monócitos/metabolismo , Monócitos/patologia , Placenta/irrigação sanguínea , Placenta/imunologia , Placenta/virologia , Gravidez , Linfócitos T/imunologia , Linfócitos T/virologia , Receptor 7 Toll-Like/genética , Receptor Toll-Like 9/genética
12.
Cancer Epidemiol ; 68: 101793, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32841926

RESUMO

BACKGROUND: Human papillomavirus (HPV) is considered the strongest epidemiologic risk factor for cervical cancer. However, it is not a sufficient cause given the high prevalence of transient infections. We examined the relationship between exposure to tobacco smoke, measured using urinary nicotine metabolite concentrations, and p16/Ki-67 co-expression in cervical smears and subsequent risk of developing CIN2+/CIN3+ lesions in HPV positive women. METHODS: This prospective longitudinal study enrolled women presenting to colposcopy with cytological abnormalities LSIL/ASCUS at the National Maternity Hospital, Dublin. Women gave a urine sample which was used to perform the Nicotine Metabolite Assay (Siemens). HPV positive (HC2) cervical smears were stained by immunocytochemistry for p16/Ki-67 (CINtec PLUS, Roche). Two year follow-up data, including histological diagnosis, was collected for each woman. Crude and adjusted odds ratios were calculated using logistic regression to investigate associations between tobacco smoke, p16/Ki-67 positivity and CIN2+/CIN3 + . RESULTS: In total, 275 HPV positive women were included. Women with nicotine metabolite concentrations above 500 ng/mL, indicative of smoking, were classified as smokers. Smokers were at an increased risk of testing positive for p16/Ki-67 (OR 1.678; 1.027-2.740) and CIN2+ and CIN3+ (OR 1.816; 1.107-2.977 and OR 2.453; 1.200-5.013) in compared to non-smokers. In p16/Ki-67 positive women, smoking further increased their risk of CIN2+/CIN3+ (OR 2.290; 1.017-5.159 and OR 3.506 (1.534-8.017). CONCLUSION: HPV positive women exposed to tobacco smoke are at a higher risk of testing positive for p16/Ki-67 co-expression. Risk of high-grade disease is almost doubled in women who are exposed to tobacco smoke.


Assuntos
Neoplasia Intraepitelial Cervical/epidemiologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Antígeno Ki-67/metabolismo , Nicotina/urina , Infecções por Papillomavirus/complicações , Poluição por Fumaça de Tabaco/análise , Neoplasias do Colo do Útero/epidemiologia , Adolescente , Adulto , Neoplasia Intraepitelial Cervical/metabolismo , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Colposcopia , Feminino , Humanos , Estudos Longitudinais , Gradação de Tumores , Teste de Papanicolaou , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Gravidez , Estudos Prospectivos , Poluição por Fumaça de Tabaco/efeitos adversos , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem
13.
Eur J Cancer Care (Engl) ; 29(4): e13241, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32432814

RESUMO

INTRODUCTION: Prevalence rates of human papillomavirus positive (HPV+) head and neck cancers (HNC) have increased over the last decades. Communicating about HPV is an increasingly relevant part of HNC patient care. This systematic review was conducted to explore healthcare professionals' (HCP) views and experiences of discussing HPV with HNC patients. It also examined perceptions among different HCP groups of their professional roles in HPV discussions. METHODS: A narrative synthesis of qualitative research was conducted. Three databases-Embase, PsycINFO and CINAHL+-were searched from January 2007 to August 2018. Relevant data were extracted and synthesised thematically. RESULTS: Five studies were identified: four were qualitative and one used mixed methods. HCPs varied in their experience and views of discussing HPV. HCPs who engaged in these discussions believed they were beneficial for patients. All HCPs described the need to address their HPV knowledge deficits in order to provide clear HPV information. Changes in professional roles which were linked to HPV communication for HCPs involved in HNC patient care were also evident. CONCLUSIONS: Effective HPV discussions are an important part of patient-provider interactions. Evidence-based interventions and professional development activities which support HCPs in their HPV discussions with patients would be valuable.


Assuntos
Atitude do Pessoal de Saúde , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Educação de Pacientes como Assunto , Papel Profissional , Carcinoma de Células Escamosas de Cabeça e Pescoço , Comunicação , Auxiliares de Odontologia , Odontólogos , Pessoal de Saúde , Humanos , Enfermeiras e Enfermeiros , Oncologistas , Relações Profissional-Paciente , Pesquisa Qualitativa , Cirurgiões
14.
Breast Cancer Res Treat ; 181(3): 571-580, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32378053

RESUMO

PURPOSE: The association between pathological complete response (pCR) in patients receiving neoadjuvant chemotherapy (NAC) for breast cancer and Circulating Tumour Cells (CTCs) is not clear. The aim of this study was to assess whether CTC enumeration could be used to predict pathological response to NAC in breast cancer as measured by the Miller-Payne grading system. METHODS: Twenty-six patients were recruited, and blood samples were taken pre- and post-NAC. CTCs were isolated using the ScreenCell device and stained using a modified Giemsa stain. CTCs were enumerated by 2 pathologists and classified as single CTCs, doublets, clusters/microemboli and correlated with the pathological response as measured by the Miller-Payne grading system. χ2 or ANOVA was performed in SPSS 24.0 statistics software for associations. RESULTS: 89% of patients had invasive ductal carcinoma (IDC) and 11% invasive lobular carcinoma (ILC). At baseline 85% of patients had CTCs present, median 7 (0-161) CTCs per 3 ml of whole blood. Post-chemotherapy, 58% had an increase in CTCs. This did not correlate with the Miller-Payne grade of response. No significant association was identified between the number of CTCs and clinical characteristics; however, we did observe a correlation between pre-treatment CTC counts and body mass index, p < 0.05. CONCLUSIONS: Patients with a complete response to NAC still had CTCs present, suggesting enumeration is not sufficient to aid surgery stratification. Additional characterisation and larger studies are needed to further characterise CTCs isolated pre- and post-chemotherapy. Long-term follow-up of these patients will determine the significance of CTCs in NAC breast cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Terapia Neoadjuvante/mortalidade , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/metabolismo , Estudos de Coortes , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Células Neoplásicas Circulantes/efeitos dos fármacos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida
15.
Oral Oncol ; 105: 104670, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32279011

RESUMO

OBJECTIVES: There is no consensus on the optimal approach to human papilloma virus (HPV) testing in oropharyngeal squamous cell carcinoma (OPSCC). Our objective was to classify OPSCC as HPV positive or negative based on (1) morphology alone, (2) p16 status alone, (3) combined morphology and p16 status with additional HPV testing in discordant cases in keeping with 2012 College of American Pathologists (CAP) guidelines (combined approach), and to evaluate and compare survival outcomes. MATERIALS AND METHODS: Retrospective review of 168 patients, 146 with OPSCC and 22 with cervical SCC of unknown primary site (SCCUP). Morphology was classified as keratinizing or non-keratinizing, p16 immunohistochemistry (IHC) performed and additional HPV DNA PCR testing undertaken in cases in which morphology and p16 status were discordant. Survival statistics were evaluated and compared for the 3 different approaches to classification. RESULTS: On univariate analysis all 3 classification methods significantly predicted for overall survival (OS). Both p16 status and the combined approach also predicted for disease specific survival (DSS), whereas morphology fell just outside significance (p = 0.06). On multivariate analysis only the combined approach retained significance for both OS and DSS, whilst morphology was also significant for DSS. CONCLUSIONS: Our findings confirm that tumour morphology significantly predicts for survival in OPSCC. However, we found combined tumour morphology and p16 IHC, with additional testing for discordant cases to be superior to either morphology or p16 IHC alone. Further study is required to establish the optimal testing method for HPV in OPSCC particularly in low prevalence populations.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/complicações , Feminino , Humanos , Masculino , Infecções por Papillomavirus/virologia , Estudos Retrospectivos
16.
Head Neck Pathol ; 14(3): 606-615, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31552619

RESUMO

Human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCC) tend to have good outcomes, however a subset does not share this favourable prognosis. The aim of this paper is to investigate the utility of tumour cell anaplasia and multinucleation as prognostic markers in oropharyngeal squamous cell carcinoma. Retrospective review of 104 patients with OPSCC or squamous cell carcinoma of unknown primary site (SCCUP) who underwent primary resection and/or lymph node dissection. Slides of both primary and nodal metastatic disease were assessed for the presence of anaplasia and multinucleation. 53 patients were HPV-positive. Anaplasia was more frequent in males (p = 0.005), smokers (p = 0.003), and HPV-negative disease (p = 0.04). HPV status and > 10 pack-year smoking history were independent predictors of recurrence-free survival (RFS) and disease-specific survival (DSS). Neither anaplasia, nor multinucleation, at the primary site or in cervical metastases, had any significant impact on RFS or DSS. We did not find either anaplasia or multinucleation to have any significant prognostic impact in OPSCC. However, given the small number of adverse events in the HPV-positive cohort, we may have lacked sufficient power to detect significance in what was the subgroup of primary interest. Our study highlights the challenge of identifying markers of poor prognosis in HPV-positive OPSCC.


Assuntos
Neoplasias Bucais/patologia , Neoplasias Faríngeas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Feminino , Humanos , Masculino , Gradação de Tumores/métodos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Prognóstico , Estudos Retrospectivos
17.
Cancer Cytopathol ; 127(4): 240-246, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30825407

RESUMO

BACKGROUND: To the authors' knowledge, published studies reporting on the performance of the FocalPoint GS (FPGS) imaging system have yielded conflicting results to date. However, the results of the MAVARIC study indicated that the FPGS "No Further Review" (NFR) aspect of the technology demonstrated potential and warranted further investigation. The current validation study was performed prior to implementing the NFR slide reporting technology within the routine cervical screening program in Wales, United Kingdom. METHODS: A total of 45,317 SurePath liquid-based cytology cervical screening samples were submitted for FPGS scanning by 4 Welsh laboratories between 2006 and 2011. The current study (Computer Assisted Evaluation, Screening and Reporting [CAESAR]), reports on a comparison between slides categorized as NFR (8130 slides) and slides manually screened as negative (93,473 slides). Both interventions had a subsequent negative quality control screen. RESULTS: The histological outcome rates of cervical intraepithelial neoplasia 2 (CIN-2) (high-grade squamous intraepithelial lesion or worse [HSIL+]) at 2 years and subsequently 3 years after an FPGS NFR result versus a manually screened negative result were compared. Significantly fewer cases were detected in the NFR cohort compared with the manually screened cohort (P = .043 at 2 years and P = .027 at 3 years). When these cases were subcategorized as cancers and precancers, the interval cancer prevalence between NFR and manually screened samples at 2 years and 3 years was similar; however, the interval precancer prevalence for FPGS NFR was significantly lower (P = .023 at 2 years and P = .026 at 3 years) at approximately one-half that of manual screening. CONCLUSIONS: The negative predictive potential of the FPGS NFR technology is higher than that of manual screening, and the technology has quality/throughput benefits to support and enhance a laboratory cervical screening service.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Detecção Precoce de Câncer/normas , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal/métodos , Esfregaço Vaginal/normas , Adulto , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Pessoa de Meia-Idade , Teste de Papanicolaou , Prognóstico , Controle de Qualidade , Esfregaço Vaginal/instrumentação , Adulto Jovem
18.
J Biophotonics ; 12(7): e201800377, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30653819

RESUMO

Patient samples are unique and often irreplaceable. This allows biobanks to be a valuable source of material. The aim of this study was to assess the ability of Raman spectroscopy to screen for histologically confirmed cases of Cervical Intraepithelial neoplasia (CIN) using biobanked liquid based cytology (LBC) samples. Two temperatures for long term storage were assessed; 80°C and -25°C. The utility of Raman spectroscopy for the detection of CIN was compared for fresh LBC samples and biobanked LBC samples. Two groups of samples were used for the study with one group associated with disease (CIN 3) and the other associated with no disease (cytology negative). The data indicates that samples stored at -80°C are not suitable for assessment by Raman spectroscopy due to a lack of cellular material and the presence of cellular debris. However, the technology can be applied to fresh LBC samples and those stored at -25°C and is, moreover, effective in the discrimination of negative samples from those where CIN 3 has been confirmed. Pooled fresh and biobanked samples are also amenable to the technology and achieve a similar sensitivity and specificity for CIN 3. This study demonstrates that cervical cytology samples stored within biobanks at temperatures that preclude cell lysis can act as a useful resource for Raman spectroscopy and will facilitate research and translational studies in this area.


Assuntos
Bancos de Espécimes Biológicos , Análise Espectral Raman , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Feminino , Humanos
19.
PLoS One ; 13(12): e0208482, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30543647

RESUMO

BACKGROUND: Primary care practitioners (PCP) play key roles in cervical cancer prevention. Human papillomavirus (HPV) knowledge is an important influence on PCPs' cervical cancer prevention-related behaviours. We investigated HPV knowledge, and associated factors, among general practitioners (GPs) and practice nurses. METHODS: A survey, including factual questions about HPV infection and vaccination, was mailed to GPs and practice nurses in Ireland. Multivariable logistic regression was used to determine which PCPs had low knowledge (questions correctly answered: infection ≤5/11; vaccination: ≤4/10). Questions least often answered correctly were identified. RESULTS: 697 PCPs participated. For HPV infection, GPs and practice nurses answered a median of nine and seven questions correctly, respectively (p<0.001). Significantly associated with low HPV infection knowledge were: being a practice nurse/male GP; working fewer hours/week; not having public patients; and having never taken a cervical smear. For HPV vaccination, both GPs and practice nurses answered a median of six questions correctly (p = 0.248). Significantly associated with low HPV vaccination knowledge were: being a practice nurse/male GP; working more years in general practice, fewer hours/week, in a smaller practice or in a practice not specialising in women's health; and having never taken a smear. Six HPV infection questions, and seven HPV vaccination questions, were not answered correctly by >⅓ of PCPs. CONCLUSIONS: There are important limitations in HPV infection and vaccination knowledge among PCPs. By identifying factors associated with poor knowledge, and areas of particular uncertainty, these results can inform development of professional education initiatives thereby ensuring women have access to uniformly high-quality HPV-related information and advice.


Assuntos
Educação Médica Continuada/organização & administração , Clínicos Gerais/educação , Clínicos Gerais/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Papillomaviridae , Adulto , Estudos Transversais , Educação Médica Continuada/métodos , Educação Profissionalizante/métodos , Educação Profissionalizante/organização & administração , Feminino , Humanos , Irlanda/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/terapia , Vacinas contra Papillomavirus/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde , Atenção Primária à Saúde/estatística & dados numéricos , Inquéritos e Questionários , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinação/psicologia , Adulto Jovem
20.
Diagn Cytopathol ; 46(12): 987-992, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30284405

RESUMO

BACKGROUND: The aim of this study was to evaluate the clinical performance of the Cobas 4800 HPV test and the Aptima HPV assay for the detection of CIN2+ disease in women referred to colposcopy with minor cytological abnormalities. METHODS: ThinPrep liquid-based cytology samples were collected from 562 women referred to colposcopy with minor cytological abnormalities. HPV testing by both assays was performed on these samples. Clinical performances for detection of histologically diagnosed CIN2+ and CIN3+ were calculated. RESULTS: HPV prevalence by the Cobas 4800 HPV test was 58.2% and 53.0% women tested positive with the Aptima HPV assay in the entire study population. The Aptima HPV assay and the Cobas 4800 HPV test displayed equivalent sensitivity of 90.2% (95%CI, 83.4-94.9) for the detection of CIN2+ disease. However, the Aptima HPV assay displayed greater specificity of 61.0% (95% CI, 54.0-68.0) when compared to the Cobas 4800 HPV test 53.0% (95% CI, 46.0-60.0), and this was significantly higher (P = .0004). The Aptima HPV assay also displayed higher specificity 76.5% (95% CI, 66.0-85.0) in the ASCUS category in comparison to the Cobas 4800 HPV test 65.0% (95% 54.0-75.0) which was statistically significant (P = .004). CONCLUSIONS: Both the tests displayed similar sensitivity. However, the Aptima HPV assay was significantly more specific in the identification of women with CIN2+ disease in a colposcopy referral population.


Assuntos
Bioensaio/métodos , Colposcopia/métodos , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Adulto , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Sensibilidade e Especificidade , Esfregaço Vaginal/métodos
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