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1.
Medicine (Baltimore) ; 99(11): e18668, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32176025

RESUMEN

This study aimed to compare the sirtuin 2 (SIRT2) expression between tumor tissue and adjacent tissue, and to investigate the association of tumor SIRT2 expression with clinical characteristics and survival profiles in cervical cancer patients.One hundred ninety-one cervical cancer patients were reviewed in this retrospective study. All patients underwent surgical resection and had well-preserved tumor tissue and adjacent tissue, which were obtained for SIRT2 expression detection by immunohistochemistry (IHC). Clinical parameters were obtained. Disease free survival (DFS) and overall survival (OS) were calculated.Both SIRT2 expression by IHC score (P < .001) and the percentage of SIRT2 high expression (defined as IHC score >3) (P < .001) were declined in tumor tissue compared with paired adjacent tissue. In addition, SIRT2 expression in tumor tissue was negatively correlated with tumor size (P = .047), lymph node metastasis (P = .009) and FIGO stage (P = .001). And the DFS (P = .007) as well as OS (P = .008) were better in patients with SIRT2 high expression compared with patents with SIRT2 low expression. Univariate Cox's proportional hazards regression model analyses revealed that high SIRT2 expression in tumor tissue was a predictive factor for more prolonged DFS (P = .009) and OS (P = .011), while multivariate Cox's proportional hazards regression model analysis disclosed that it lacks independent predictive value for DFS (P = .084) or OS (P = .132).SIRT2 expression exhibits potential to serve as a biomarker for disease surveillance and prognosis in the management of cervical cancer patients.


Asunto(s)
Sirtuina 2/metabolismo , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Cuello del Útero/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Sirtuina 2/análisis , Análisis de Supervivencia , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/mortalidad
2.
Medicine (Baltimore) ; 99(11): e19131, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32176038

RESUMEN

A collision tumor is defined by co-existence of two adjacent tumors which are histologically distinct. Little is known about the clinical manifestation, treatment, and prognosis of cervical collision cancer. The objective of the study was to investigate the management and prognosis of patients with cervical collision cancer.We retrospectively reviewed and enrolled patients with cervical collision carcinoma from 2010 to 2018 in two institutions (West China Hospital and West China Second University Hospital). The clinical presentation, pathology, treatment, and prognosis of patients with collision carcinoma of the uterine cervix were retrospectively reviewed. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.A total of 24 patients were included in this study. The proportion of cervical collision carcinoma was 0.4% in the cervical carcinoma cohort (24/6015). The median age of the patients with cervical collision cancer was 42 years. The most common presenting symptom was cervical contactive bleeding. There were 23 patients classified as International Federation of Gynecology and Obstetrics (FIGO) stage IA1-IIB. All patients except one received radical hysterectomy, in which 21 patients received bilateral salpingo-oophorectomy (BSO) and pelvic lymphadenectomy in addition. There were 16 patients who received adjuvant chemotherapy or chemoradiotherapy. The median follow-up time was 21 months. No patient death was observed. Recurrence only occurred in two patients. The 5-year OS rates and PFS rates were 100% and 91.7%, respectively.This study revealed that cervical collision cancer was a type of rare cervical cancer with good prognosis. Cervical collision cancer responded well to the same treatment methods as the cervical squamous cell carcinoma and was associated with few recurrence and long survival.


Asunto(s)
Neoplasias Primarias Múltiples/patología , Neoplasias del Cuello Uterino/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adulto , Anciano , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , China , Terapia Combinada , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Primarias Múltiples/mortalidad , Neoplasias Primarias Múltiples/terapia , Panicum , Supervivencia sin Progresión , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/terapia
4.
Lancet ; 395(10224): 575-590, 2020 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-32007141

RESUMEN

BACKGROUND: The WHO Director-General has issued a call for action to eliminate cervical cancer as a public health problem. To help inform global efforts, we modelled potential human papillomavirus (HPV) vaccination and cervical screening scenarios in low-income and lower-middle-income countries (LMICs) to examine the feasibility and timing of elimination at different thresholds, and to estimate the number of cervical cancer cases averted on the path to elimination. METHODS: The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC), which consists of three independent transmission-dynamic models identified by WHO according to predefined criteria, projected reductions in cervical cancer incidence over time in 78 LMICs for three standardised base-case scenarios: girls-only vaccination; girls-only vaccination and once-lifetime screening; and girls-only vaccination and twice-lifetime screening. Girls were vaccinated at age 9 years (with a catch-up to age 14 years), assuming 90% coverage and 100% lifetime protection against HPV types 16, 18, 31, 33, 45, 52, and 58. Cervical screening involved HPV testing once or twice per lifetime at ages 35 years and 45 years, with uptake increasing from 45% (2023) to 90% (2045 onwards). The elimination thresholds examined were an average age-standardised cervical cancer incidence of four or fewer cases per 100 000 women-years and ten or fewer cases per 100 000 women-years, and an 85% or greater reduction in incidence. Sensitivity analyses were done, varying vaccination and screening strategies and assumptions. We summarised results using the median (range) of model predictions. FINDINGS: Girls-only HPV vaccination was predicted to reduce the median age-standardised cervical cancer incidence in LMICs from 19·8 (range 19·4-19·8) to 2·1 (2·0-2·6) cases per 100 000 women-years over the next century (89·4% [86·2-90·1] reduction), and to avert 61·0 million (60·5-63·0) cases during this period. Adding twice-lifetime screening reduced the incidence to 0·7 (0·6-1·6) cases per 100 000 women-years (96·7% [91·3-96·7] reduction) and averted an extra 12·1 million (9·5-13·7) cases. Girls-only vaccination was predicted to result in elimination in 60% (58-65) of LMICs based on the threshold of four or fewer cases per 100 000 women-years, in 99% (89-100) of LMICs based on the threshold of ten or fewer cases per 100 000 women-years, and in 87% (37-99) of LMICs based on the 85% or greater reduction threshold. When adding twice-lifetime screening, 100% (71-100) of LMICs reached elimination for all three thresholds. In regions in which all countries can achieve cervical cancer elimination with girls-only vaccination, elimination could occur between 2059 and 2102, depending on the threshold and region. Introducing twice-lifetime screening accelerated elimination by 11-31 years. Long-term vaccine protection was required for elimination. INTERPRETATION: Predictions were consistent across our three models and suggest that high HPV vaccination coverage of girls can lead to cervical cancer elimination in most LMICs by the end of the century. Screening with high uptake will expedite reductions and will be necessary to eliminate cervical cancer in countries with the highest burden. FUNDING: WHO, UNDP, UN Population Fund, UNICEF-WHO-World Bank Special Program of Research, Development and Research Training in Human Reproduction, Canadian Institute of Health Research, Fonds de recherche du Québec-Santé, Compute Canada, National Health and Medical Research Council Australia Centre for Research Excellence in Cervical Cancer Control.


Asunto(s)
Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino/prevención & control , Adulto , Países en Desarrollo , Detección Precóz del Cáncer/métodos , Estudios de Factibilidad , Femenino , Humanos , Incidencia , Renta , Tamizaje Masivo/métodos , Modelos Biológicos , Infecciones por Papillomavirus/complicaciones , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Vacunación
5.
Lancet ; 395(10224): 591-603, 2020 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-32007142

RESUMEN

BACKGROUND: WHO is developing a global strategy towards eliminating cervical cancer as a public health problem, which proposes an elimination threshold of four cases per 100 000 women and includes 2030 triple-intervention coverage targets for scale-up of human papillomavirus (HPV) vaccination to 90%, twice-lifetime cervical screening to 70%, and treatment of pre-invasive lesions and invasive cancer to 90%. We assessed the impact of achieving the 90-70-90 triple-intervention targets on cervical cancer mortality and deaths averted over the next century. We also assessed the potential for the elimination initiative to support target 3.4 of the UN Sustainable Development Goals (SDGs)-a one-third reduction in premature mortality from non-communicable diseases by 2030. METHODS: The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC) involves three independent, dynamic models of HPV infection, cervical carcinogenesis, screening, and precancer and invasive cancer treatment. Reductions in age-standardised rates of cervical cancer mortality in 78 low-income and lower-middle-income countries (LMICs) were estimated for three core scenarios: girls-only vaccination at age 9 years with catch-up for girls aged 10-14 years; girls-only vaccination plus once-lifetime screening and cancer treatment scale-up; and girls-only vaccination plus twice-lifetime screening and cancer treatment scale-up. Vaccination was assumed to provide 100% lifetime protection against infections with HPV types 16, 18, 31, 33, 45, 52, and 58, and to scale up to 90% coverage in 2020. Cervical screening involved HPV testing at age 35 years, or at ages 35 years and 45 years, with scale-up to 45% coverage by 2023, 70% by 2030, and 90% by 2045, and we assumed that 50% of women with invasive cervical cancer would receive appropriate surgery, radiotherapy, and chemotherapy by 2023, which would increase to 90% by 2030. We summarised results using the median (range) of model predictions. FINDINGS: In 2020, the estimated cervical cancer mortality rate across all 78 LMICs was 13·2 (range 12·9-14·1) per 100 000 women. Compared to the status quo, by 2030, vaccination alone would have minimal impact on cervical cancer mortality, leading to a 0·1% (0·1-0·5) reduction, but additionally scaling up twice-lifetime screening and cancer treatment would reduce mortality by 34·2% (23·3-37·8), averting 300 000 (300 000-400 000) deaths by 2030 (with similar results for once-lifetime screening). By 2070, scaling up vaccination alone would reduce mortality by 61·7% (61·4-66·1), averting 4·8 million (4·1-4·8) deaths. By 2070, additionally scaling up screening and cancer treatment would reduce mortality by 88·9% (84·0-89·3), averting 13·3 million (13·1-13·6) deaths (with once-lifetime screening), or by 92·3% (88·4-93·0), averting 14·6 million (14·1-14·6) deaths (with twice-lifetime screening). By 2120, vaccination alone would reduce mortality by 89·5% (86·6-89·9), averting 45·8 million (44·7-46·4) deaths. By 2120, additionally scaling up screening and cancer treatment would reduce mortality by 97·9% (95·0-98·0), averting 60·8 million (60·2-61·2) deaths (with once-lifetime screening), or by 98·6% (96·5-98·6), averting 62·6 million (62·1-62·8) deaths (with twice-lifetime screening). With the WHO triple-intervention strategy, over the next 10 years, about half (48% [45-55]) of deaths averted would be in sub-Saharan Africa and almost a third (32% [29-34]) would be in South Asia; over the next 100 years, almost 90% of deaths averted would be in these regions. For premature deaths (age 30-69 years), the WHO triple-intervention strategy would result in rate reductions of 33·9% (24·4-37·9) by 2030, 96·2% (94·3-96·8) by 2070, and 98·6% (96·9-98·8) by 2120. INTERPRETATION: These findings emphasise the importance of acting immediately on three fronts to scale up vaccination, screening, and treatment for pre-invasive and invasive cervical cancer. In the next 10 years, a one-third reduction in the rate of premature mortality from cervical cancer in LMICs is possible, contributing to the realisation of the 2030 UN SDGs. Over the next century, successful implementation of the WHO elimination strategy would reduce cervical cancer mortality by almost 99% and save more than 62 million women's lives. FUNDING: WHO, UNDP, UN Population Fund, UNICEF-WHO-World Bank Special Program of Research, Development and Research Training in Human Reproduction, Germany Federal Ministry of Health, National Health and Medical Research Council Australia, Centre for Research Excellence in Cervical Cancer Control, Canadian Institute of Health Research, Compute Canada, and Fonds de recherche du Québec-Santé.


Asunto(s)
Neoplasias del Cuello Uterino/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Países en Desarrollo , Detección Precóz del Cáncer/métodos , Femenino , Humanos , Renta , Lactante , Recién Nacido , Tamizaje Masivo/métodos , Persona de Mediana Edad , Modelos Biológicos , Mortalidad/tendencias , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología , Vacunación/métodos , Organización Mundial de la Salud , Adulto Joven
6.
Medicine (Baltimore) ; 99(6): e19135, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32028440

RESUMEN

This study is to evaluate the screening methods of cervical cancers for rural females in Kash bachu, Xinjiang, China.A total number of 3000 married females were surveyed, and subjected to the gynecological examination. In these subjects, 1993 females received the careHPV (human papillomavirus) test, while 1007 females underwent the visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI). The subjects positive for careHPV detection were subjected to Cervista, Cobas 4800, and Aptima HPV detection, and Thinprep Cytologic Test (TCT). The subjects positive for 1 detection only received colposcopy cervical biopsy.A total of 569 subjects received the cervical biopsy, and the positive rate was 2.3% (69/3000), while the detection rate for CIN (cervical intraepithelial neoplasia) II and above levels was 1.13% (34/3000). Receiver operator characteristic (ROC) curve analysis showed that, the area under the curve (AUC) value for the careHPV test was 0.671, which was higher than the VIA/VILI (0.619), suggesting higher diagnostic value for the careHPV test. For the Cervista, Cobas 4800, Aptima HPV detection, and TCT methods, the highest AUC value was observed for the TCT method, indicating that the TCT method is the most valuable for the cervical cancer screening.The diagnostic value of careHPV test is superior to the VIA/VILA detection method. The TCT method has the greatest value for the cervical cancer screening. The Cervista HPV detection method should be considered where the conditions are limited.


Asunto(s)
Detección Precóz del Cáncer/métodos , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Biopsia , Cuello del Útero/patología , China , Colposcopía , Femenino , Humanos , Infecciones por Papillomavirus/diagnóstico , Población Rural , Neoplasias del Cuello Uterino/patología
7.
Anticancer Res ; 40(2): 999-1006, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32014945

RESUMEN

BACKGROUND/AIM: We aimed to evaluate the efficacy of high-dose-rate brachytherapy techniques selected according to pre-brachytherapy magnetic resonance imaging (MRI) findings in asymmetrical cervical cancer (ACC). PATIENTS AND METHODS: We analyzed 33 ACC patients. Asymmetric tumors were defined as those in which the difference between the distance from the cervical canal to the farthest end of the tumor [long distance (LD)] and the distance from the cervical canal to the contralateral tumor edge [short distance (SD)] is equal to or greater than 2 cm on the basis of MRI prior to treatment. On pre-treatment and pre-brachytherapy MRI, the median LDs were 40 mm and 21 mm, respectively. Patients with LD≥2 cm and LD - SD≥1 cm on pre-brachytherapy MRI received non-conventional intracavitary brachytherapy (ICBT). RESULTS: Sixteen patients (48%) received non-conventional ICBT. There was no significant difference in 3-year local control between the two treatment groups (100% vs. 81.2%, p=0.07); two patients had grade 2 radiation proctitis. CONCLUSION: Brachytherapy techniques selected according to pre-brachytherapy MRI findings were effective for ACC treatment.


Asunto(s)
Braquiterapia , Dosificación Radioterapéutica , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Braquiterapia/efectos adversos , Braquiterapia/métodos , Femenino , Humanos , Estimación de Kaplan-Meier , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Estadificación de Neoplasias , Selección de Paciente , Resultado del Tratamiento , Neoplasias del Cuello Uterino/diagnóstico
8.
BMC Public Health ; 20(1): 5, 2020 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-31906964

RESUMEN

BACKGROUND: Studies from European and non-European countries have shown that migrants utilize cervical cancer screening less often than non-migrants. Findings from Germany are inconsistent. This can be explained by several limitations of existing investigations, comprising residual confounding and data which is restricted to only some regions of the country. Using data from a large-scale and nationwide population survey and applying the Andersen Model of Health Services Use as the theoretical framework, the aim of the present study was to examine the role that different predisposing, enabling and need factors have for the participation of migrant and non-migrant women in cervical cancer screening in Germany. METHODS: We used data from the 'German Health Update 2014/2015' survey on n = 12,064 women ≥20 years of age. The outcome of interest was the participation in cancer screening (at least once in lifetime vs. no participation). The outcome was compared between the three population groups of non-migrants, migrants from EU countries and migrants from non-EU countries. We employed multivariable logistic regression to examine the role of predisposing, enabling and need factors. RESULTS: Non-EU and EU migrant women reported a lower utilization of cervical cancer screening (50.1 and 52.7%, respectively) than non-migrant women (57.2%). The differences also remained evident after adjustment for predisposing, enabling and need factors. The respective adjusted odds ratios (OR) for non-EU and EU migrants were OR = 0.67 (95%-CI = 0.55-0.81) and OR = 0.80 (95%-CI = 0.66-0.97), respectively. Differences between migrants and non-migrants were particularly pronounced for younger age groups. Self-rated health was associated with participation in screening only in non-migrants, with a poorer health being indicative of a low participation in cancer screening. CONCLUSIONS: The disparities identified are in line with findings from studies conducted in other countries and are indicative of different obstacles this population group encounters in the health system. Implementing patient-oriented health care through diversity-sensitive health services is necessary to support informed decision-making.


Asunto(s)
Detección Precóz del Cáncer/estadística & datos numéricos , Migrantes/estadística & datos numéricos , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Femenino , Alemania , Encuestas de Atención de la Salud , Humanos , Persona de Mediana Edad , Adulto Joven
9.
DNA Cell Biol ; 39(2): 255-272, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31977248

RESUMEN

Cervical squamous cell carcinoma (CESC) is a human papillomavirus-driven tumor that the underlying molecular mechanisms are unclear. This study aimed to elucidate the key candidate genes and potential mechanism in CESC by bioinformatics analysis. A total of 132 common differentially expressed genes (DEGs) were identified based on three expression profile data sets. A multivariate Cox proportional regression model was used to develop a four-gene prognostic signature. Mechanistically, the correlationship between MMP1 and tumor-infiltrating lymphocytes was further analyzed. Furthermore, annotations were investigated by Gene Ontology (GO) and The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Finally, potential drugs for CESC treatment were predicted by Connectivity Map. We profiled four genes (EFNA1, ANLN, MMP1, and ZWINT) with significant prognostic values for CESC. Multiple public available data sets were used for mRNA expression and prognostic characterization. Subsequently, GO and KEGG pathway analyses showed DEGs were mainly enriched in cell cycle, immunity, and metabolic-related pathway. We then conducted an integrated analysis of MMP1, and the expression of MMP1 showed significantly inverse association with the amount of CD8+ T cells, CD4+ T cells, and macrophages infiltration. Our findings suggest the four-gene signature may be associated with prognosis. We further revealed that MMP1 may be a novel biomarker for immunotherapy, and prognostic judgment of patients with cervical cancer.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Regulación Neoplásica de la Expresión Génica , Metaloproteinasa 1 de la Matriz/genética , Neoplasias del Cuello Uterino/genética , Carcinoma de Células Escamosas/diagnóstico , Femenino , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes/genética , Humanos , Pronóstico , Mapas de Interacción de Proteínas/genética , Neoplasias del Cuello Uterino/diagnóstico
10.
Oncology ; 98(2): 91-97, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31593942

RESUMEN

OBJECTIVE: At the end of the year 2018, a new FIGO classification for cervical cancer was published, mainly revising stage IB and introducing a new stage IIIC, which includes irrespectively of tumor size and local spread all patients with lymph node metastasis. METHODS: We retrospectively analyzed all cases of cervical cancer stage I to IIB who underwent surgery as primary treatment at our institution from 2000 until 2016 and therefore had a histological confirmation of tumor stage. We reclassified all histologies according to the new FIGO classification and calculated outcome according to the new stages. RESULTS: Out of 265 patients, 146 (55%) patients were reclassified into a higher FIGO stage. Most changes appeared within stage IB and from any stage to stage IIIC1. Kaplan-Meier curves for new stages showed a significant difference in disease-free survival (DFS) and overall survival (OS) between stages I versus II versus III (log-rank test, both p < 0.001). Overall, patients that were upstaged had a significant worse DFS (p = 0.012) and OS (p = 0.008) than patients whose stage did not change. Similar observations were made within sub-stages, when node-positive IB or IIB tumors were upstaged to IIIC tumors. CONCLUSION: The new FIGO classification for cervical cancer reflects the strong impact of lymph node metastases on survival and is a clear improvement compared to the old FIGO classification with regard to risk stratification.


Asunto(s)
Estadificación de Neoplasias/métodos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Pronóstico , Estudios Retrospectivos
11.
Lancet Psychiatry ; 7(1): 52-63, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31787585

RESUMEN

BACKGROUND: Since people with mental illness are more likely to die from cancer, we assessed whether people with mental illness undergo less cancer screening compared with the general population. METHODS: In this systematic review and meta-analysis, we searched PubMed and PsycINFO, without a language restriction, and hand-searched the reference lists of included studies and previous reviews for observational studies from database inception until May 5, 2019. We included all published studies focusing on any type of cancer screening in patients with mental illness; and studies that reported prevalence of cancer screening in patients, or comparative measures between patients and the general population. The primary outcome was odds ratio (OR) of cancer screening in people with mental illness versus the general population. The Newcastle-Ottawa Scale was used to assess study quality and I2 to assess study heterogeneity. This study is registered with PROSPERO, CRD42018114781. FINDINGS: 47 publications provided data from 46 samples including 4 717 839 individuals (501 559 patients with mental illness, and 4 216 280 controls), of whom 69·85% were women, for screening for breast cancer (k=35; 296 699 individuals with mental illness, 1 023 288 in the general population), cervical cancer (k=29; 295 688 with mental illness, 3 540 408 in general population), colorectal cancer (k=12; 153 283 with mental illness, 2 228 966 in general population), lung and gastric cancer (both k=1; 420 with mental illness, none in general population), ovarian cancer (k=1; 37 with mental illness, none in general population), and prostate cancer (k=6; 52 803 with mental illness, 2 038 916 in general population). Median quality of the included studies was high at 7 (IQR 6-8). Screening was significantly less frequent in people with any mental disease compared with the general population for any cancer (k=37; OR 0·76 [95% CI 0·72-0·79]; I2=98·53% with publication bias of Egger's p value=0·025), breast cancer (k=27; 0·65 [0·60-0·71]; I2=97·58% and no publication bias), cervical cancer (k=23; 0·89 [0·84-0·95]; I2=98·47% and no publication bias), and prostate cancer (k=4; 0·78 [0·70-0·86]; I2=79·68% and no publication bias), but not for colorectal cancer (k=8; 1·02 [0·90-1·15]; I2=97·84% and no publication bias). INTERPRETATION: Despite the increased mortality from cancer in people with mental illness, this population receives less cancer screening compared with that of the general population. Specific approaches should be developed to assist people with mental illness to undergo appropriate cancer screening, especially women with schizophrenia. FUNDING: None.


Asunto(s)
Neoplasias de la Mama , Neoplasias Colorrectales , Detección Precóz del Cáncer/estadística & datos numéricos , Trastornos Mentales/diagnóstico , Neoplasias del Cuello Uterino , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/prevención & control , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/prevención & control , Femenino , Humanos , Trastornos Mentales/fisiopatología , Prevalencia , Calidad de Vida , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control
12.
Int J Cancer ; 146(7): 1810-1818, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-31245842

RESUMEN

HPV FOCAL is a randomized control trial of cervical cancer screening. The intervention arm received baseline screening for high-risk human papillomavirus (HPV) and the control arm received liquid-based cytology (LBC) at baseline and 24 months. Both arms received 48-month exit HPV and LBC cotesting. Exit results are presented for per-protocol eligible (PPE) screened women. Participants were PPE at exit if they had completed all screening and recommended follow-up and had not been diagnosed with cervical intraepithelial neoplasia Grade 2 or worse (CIN2+) earlier in the trial. Subgroups were identified based upon results at earlier trial screening. There were 9,457 and 9,552 and women aged 25-65 randomized to control and intervention and 7,448 (77.8%) and 8,281 (86.7%), respectively, were PPE and screened. Exit cotest results were similar (p = 0.11) by arm for PPE and the relative rate (RR) of CIN2+ for intervention vs. control was RR = 0.83 (95% CI: 0.56-1.23). The RR for CIN2+ comparing intervention women baseline HPV negative to control women with negative cytology at baseline and at 24 months, was 0.68 (95% CI: 0.43-1.06). PPE women who had a negative or CIN1 colposcopy in earlier rounds had elevated rates (per 1,000) of CIN2+ at exit, control 31 (95% CI: 14-65) and intervention 43 (95% CI: 25-73). Among PPE women HPV negative at exit LBC cotesting identified little CIN2+, Rate = 0.3 (95% CI: 0.1-0.7). This per-protocol analysis found that screening with HPV using a 4-year interval is as safe as LBC with a 2-year screening interval. LBC screening in HPV negative women at exit identified few additional lesions.


Asunto(s)
Papillomaviridae , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/etiología , Adulto , Anciano , Colombia Británica/epidemiología , Neoplasia Intraepitelial Cervical/epidemiología , Neoplasia Intraepitelial Cervical/etiología , ADN Viral , Femenino , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Vigilancia en Salud Pública , Neoplasias del Cuello Uterino/diagnóstico
13.
Int J Cancer ; 146(5): 1230-1240, 2020 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-31107987

RESUMEN

Our study used a refined case-control cervical cancer Audit framework to investigate effectiveness of cervical screening, with measures of three screening failures: irregular-participation, cervical cancer developed after cytological abnormalities and after normal screening results. The register-based study included 4,254 cervical cancer cases diagnosed in Sweden during 2002-2011, and 30 population-based controls per case. We used conditional logistic regression models to examine relative risks of cervical cancer in relation to screening participation and screening results in the past two screening rounds from 6 months before cancer diagnosis. We found that women unscreened in past two screening rounds showed four times increased risk of cervical cancer compared to women screened in time (OR = 4.1, 95% CI = 3.8-4.5), and women unscreened in the previous round but screened in the most recent round also showed a statistically significantly elevated risk (OR = 1.6, 95% CI = 1.5-1.8). Women having abnormality in previous two rounds exhibited higher risk of cervical cancer compared to women screened with normal results, while having normal results in the subsequent round after the abnormality also yielded an increased risk (OR = 4.0, 95% CI = 3.2-5.1). Being screened with only normal results was associated with 89% risk reduction for squamous cell cancer, compared to women unscreened, but only 60% reduction for adenocarcinoma. Our findings emphasize the importance of routine participation in cervical screening and suggest that management of abnormalities, as well as sensitivity of the test, warrants improvement especially for preventing cervical adenocarcinoma. The Audit framework serves as routine evaluation model and the findings benchmark for future evaluation of changes in screening practice.


Asunto(s)
Detección Precóz del Cáncer/estadística & datos numéricos , Tamizaje Masivo/organización & administración , Auditoría Médica/estadística & datos numéricos , Participación del Paciente/estadística & datos numéricos , Neoplasias del Cuello Uterino/epidemiología , Adulto , Anciano , Benchmarking/estadística & datos numéricos , Estudios de Casos y Controles , Cuello del Útero/patología , Femenino , Humanos , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Prueba de Papanicolaou/estadística & datos numéricos , Embarazo , Evaluación de Programas y Proyectos de Salud , Sistema de Registros/estadística & datos numéricos , Medición de Riesgo , Suecia/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Adulto Joven
14.
Int J Cancer ; 146(7): 2047-2058, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-31732968

RESUMEN

More than one-third of patients with locally advanced cervical cancer do not respond to chemoradiation therapy (CRT). We aimed to characterize the transcriptional landscape of paired human cervical tumors before and during CRT in order to gain insight into the evolution of treatment response and to elucidate mechanisms of treatment resistance. We prospectively collected cervical tumor biopsies from 115 patients both before and 3 weeks into CRT. RNA-sequencing, Gene Set Enrichment Analysis and HPV gene expression were performed on 20 paired samples that had adequate neoplastic tissue mid-treatment. Tumors from patients with no evidence of disease (NED) at last follow-up had enrichment in pathways related to the immune response both pretreatment and mid-treatment, while tumors from patients dead of disease (DOD) demonstrated enrichment in biosynthetic and mitotic pathways but not in immune-related pathways. Patients DOD had decreased expression of T-cell and cytolytic genes and increased expression of PD-L2 mid-treatment compared to patients NED. Histological and immunohistochemical analysis revealed a decrease in tumor-associated lymphocytes (TAL) during CRT in all patients but tumors from patients DOD had a significantly more pronounced decrease in TALs and CD8+ cells mid-treatment, which was validated in a larger mid-treatment cohort. Finally, patients DOD retained more HPV E6/E7 gene expression during CRT and this was associated with increased expression of genes driving mitosis, which was corroborated in vitro. Our results suggest that decreased local immune response and retained HPV gene expression may be acting together to promote treatment resistance during CRT in patients with cervical cancer.


Asunto(s)
Resistencia a Antineoplásicos , Regulación Viral de la Expresión Génica , Inmunomodulación/efectos de los fármacos , Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Terapia Combinada , Resistencia a Antineoplásicos/inmunología , Femenino , Perfilación de la Expresión Génica , Humanos , Metástasis Linfática , Estadificación de Neoplasias , Papillomaviridae/clasificación , Papillomaviridae/inmunología , Infecciones por Papillomavirus/inmunología , Pronóstico , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/mortalidad
15.
Acta Cytol ; 64(1-2): 63-70, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30889579

RESUMEN

The association between high-risk genotypes of human papillomavirus (hr-HPV) and cervical cancer is well established. As hr-HPV testing is rapidly becoming a part of routine cervical cancer screening, either in conjunction with cytology or as primary testing, the management of hr-HPV-positive women has to be tailored in a way that increases the detection of cervical abnormalities while decreasing unnecessary colposcopic biopsies or other invasive procedures. In this review, we discuss the overall utility and strategies of hr-HPV testing, as well as the advantages and limitations of potential triage strategies for hr-HPV-positive women, including HPV genotyping, p16/Ki-67 dual staining, and methylation assays.


Asunto(s)
Citodiagnóstico/métodos , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Detección Precóz del Cáncer/métodos , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Papillomaviridae/fisiología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Triaje , Neoplasias del Cuello Uterino/complicaciones
16.
Acta Cytol ; 64(1-2): 155-165, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30982025

RESUMEN

The Papanicolaou (PAP) test is widely used to screen for cervical cancer. All high-grade lesions such as atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), and high-grade squamous intraepithelial lesion, identified on a PAP test should be followed-up by a confirmatory cervical biopsy. In this review, we discuss the challenges in interpreting cervical tissue specimens and the various ancillary techniques used in the evaluation of cervical dysplasia. Ancillary studies include deeper levels, p16 immunohistochemistry (IHC), human papillomavirus (HPV) testing, and, importantly, cyto-histologic correlation. Of these, p16 IHC is consistently sensitive and specific for detecting HSIL. HPV RNA in situ hybridization (ISH) is a newer technique with excellent sensitivity and specificity for detecting virally infected cells and it may be more broadly applicable to both low- and high-grade squamous intraepithelial lesions.


Asunto(s)
Células Escamosas Atípicas del Cuello del Útero/patología , Neoplasia Intraepitelial Cervical/patología , Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Biopsia , Neoplasia Intraepitelial Cervical/diagnóstico , Legrado , Femenino , Humanos , Prueba de Papanicolaou/métodos , Papillomaviridae/fisiología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/diagnóstico
17.
Int J Cancer ; 146(3): 810-818, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30980692

RESUMEN

Primary prevention through the use of human papillomavirus (HPV) vaccination is expected to impact both cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS). While CIN is well described, less is known about the epidemiology of AIS, a rare cervical precancer. We identified AIS and CIN grade 3 (CIN3) cases through population-based surveillance, and analyzed data on HPV types and incidence trends overall, and among women screened for cervical cancer. From 2008 to 2015, 470 AIS and 6,587 CIN3 cases were identified. The median age of women with AIS was older than those with CIN3 (35 vs. 31 years; p < 0.01). HPV16 was the most frequently detected type in both AIS and CIN3 (57% in AIS; 58% in CIN3), whereas HPV18 was the second most common type in AIS and less common in CIN3 (38% vs. 5%; p < 0.01). AIS lesions were more likely than CIN3 lesions to be positive for high-risk types targeted by the bivalent and quadrivalent vaccines (HPV16/18, 92% vs. 63%; p < 0.01), and 9-valent vaccine (HPV16/18/31/33/45/52/58, 95% vs. 87%; p < 0.01). AIS incidence rates decreased significantly in the 21-24 year age group (annual percent change [APC] overall: -22.1%, 95% CI: -33.9 to -8.2; APC among screened: -16.1%, 95% CI: -28.8 to -1.2), but did not decrease significantly in any older age group. This report on the largest number of genotyped AIS cases to date suggests an important opportunity for vaccine prevention of AIS, and is the first to document a decline in AIS incidence rates among young women during the vaccine era.


Asunto(s)
Adenocarcinoma in Situ/epidemiología , Neoplasia Intraepitelial Cervical/epidemiología , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Lesiones Precancerosas/epidemiología , Adenocarcinoma in Situ/prevención & control , Adenocarcinoma in Situ/virología , Adolescente , Adulto , Factores de Edad , Neoplasia Intraepitelial Cervical/prevención & control , Neoplasia Intraepitelial Cervical/virología , ADN Viral/aislamiento & purificación , Femenino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Incidencia , Tamizaje Masivo/estadística & datos numéricos , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/virología , Vacunas contra Papillomavirus/uso terapéutico , Lesiones Precancerosas/prevención & control , Lesiones Precancerosas/virología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología , Adulto Joven
18.
Int J Cancer ; 146(3): 617-626, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30861114

RESUMEN

US guidelines recommend that most women older than 65 years cease cervical screening after two consecutive negative cotests (concurrent HPV and cytology tests) in the previous 10 years, with one in the last 5 years. However, this recommendation was based on expert opinion and modeling rather than empirical data on cancer risk. We therefore estimated the 5-year risks of cervical precancer (cervical intraepithelial neoplasia grade 3 or adenocarcinoma in situ [CIN3]) after one, two and three negative cotests among 346,760 women aged 55-64 years undergoing routine cotesting at Kaiser Permanente Northern California (2003-2015). Women with a history of excisional treatment or CIN2+ were excluded. No woman with one or more negative cotests was diagnosed with cancer during follow-up. Five-year risks of CIN3 after one, two, and three consecutive negative cotests were 0.034% (95% CI: 0.023%-0.046%), 0.041% (95% CI: 0.007%-0.076%) and 0.016% (95% CI: 0.000%-0.052%), respectively (ptrend < 0.001). These risks did not appreciably differ by a positive cotest result prior to the one, two or three negative cotest(s). Since CIN3 risks after one or more negative cotests were significantly below a proposed 0.12% CIN3+ risk threshold for a 5-year screening interval, a longer screening interval in these women is justified. However, the choice of how many negative cotests provide sufficient safety against invasive cancer over a woman's remaining life represents a value judgment based on the harms versus benefits of continued screening. Ideally, this guideline should be informed by longer-term follow-up given that exiting is a long-term decision.


Asunto(s)
Adenocarcinoma in Situ/epidemiología , Neoplasia Intraepitelial Cervical/epidemiología , Infecciones por Papillomavirus/epidemiología , Lesiones Precancerosas/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Adenocarcinoma in Situ/diagnóstico , Adenocarcinoma in Situ/patología , California/epidemiología , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/patología , Cuello del Útero/patología , Detección Precóz del Cáncer/normas , Femenino , Humanos , Tamizaje Masivo/normas , Persona de Mediana Edad , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Guías de Práctica Clínica como Asunto , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Estudios Prospectivos , Medición de Riesgo/estadística & datos numéricos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología
19.
J Clin Pathol ; 73(1): 30-34, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31315894

RESUMEN

AIMS: The purpose of the present study was to elucidate the presence of human herpesvirus 6A (HHV-6A), HHV-6B and HHV-7 in samples of the uterine cervix through detection of viral DNA. We analysed normal tissues, samples with low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs). We correlated the presence of HHV-6 and HHV-7 with the finding of human papillomavirus (HPV) in mucosal samples. METHODS: Cervical samples were examined and grouped as follows: group 1 (n=29), normal cytology; group 2 (n=61), samples with LSIL; group 3 (n=35), samples with HSIL. Molecular biology examinations were performed in all samples to detect HHV-6, HHV-7 and HPV DNA and to typify HHV-6 species. RESULTS: Group 1: normal cytology and HPV (-): HHV-6: 6.8% (2/29), HHV-7: 79.3% (23/29); group 2: LSIL and HPV (-): HHV-6: 93.1% (27/29), HHV-7: 96.5% (28/29); LSIL and HPV (+): HHV-6: 0% (0/32), HHV-7: 90.6% (29/32); group 3: HSIL and HPV (-): HHV-6: 20% (2/10), HHV-7: 70% (7/10); HSIL HPV (+): HHV-6: 12% (3/25), HHV-7: 68% (17/25). HHV-6A DNA was not detected in any samples. CONCLUSIONS: (1) Both HHV-6 and HHV-7 infect the mucosal cells of the cervix with higher prevalence of HHV-7. (2) The higher prevalence of HHV-6 in LSIL HPV (-) samples compared with those with normal cytology indicates that it constitutes a possible risk factor for atypia production. (3) The presence of HHV-7 in all samples questions its role in the production of atypia. (4) The finding of HHV-6 and HHV-7 suggests that the cervical mucosa is a possible transmission pathway for these viruses.


Asunto(s)
Neoplasia Intraepitelial Cervical/diagnóstico , ADN Viral/genética , Herpesvirus Humano 6/genética , Herpesvirus Humano 7/genética , Técnicas de Diagnóstico Molecular , Infecciones por Roseolovirus/diagnóstico , Lesiones Intraepiteliales Escamosas de Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adolescente , Adulto , Argentina , Neoplasia Intraepitelial Cervical/genética , Neoplasia Intraepitelial Cervical/virología , Femenino , Pruebas de ADN del Papillomavirus Humano , Humanos , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/virología , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Infecciones por Roseolovirus/genética , Infecciones por Roseolovirus/transmisión , Infecciones por Roseolovirus/virología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/genética , Lesiones Intraepiteliales Escamosas de Cuello Uterino/virología , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/virología , Adulto Joven
20.
BJOG ; 127(1): 58-68, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31541495

RESUMEN

OBJECTIVES: To estimate long-term cervical intraepithelial neoplasia grade 3 (CIN3) risks associated with different triage strategies for human papillomavirus positive (HPV+) women with a view to reducing unnecessary referrals. DESIGN: The ARTISTIC trial cohort was recruited in Manchester in 2001-03 and was followed up for CIN3 and cancer notification through national registration until December 2015. RESULTS: The 10-year cumulative risk of CIN3+ was much higher for women with HPV16/18 infection (19.4%, 95% CI 15.8-23.8% with borderline/low-grade cytology and 10.7%, 95% CI 8.3-13.9% with normal cytology) than for those with other HPV types (7.3%, 95% CI 5.4-9.7% with borderline/low-grade cytology and 3.2%, 95% CI 2.2-4.5% with normal cytology). Among the 379 women with normal to low-grade cytology and new HPV infection, the 10-year cumulative CIN3+ risk was 2.9% (95% CI 1.6-5.2%). CONCLUSIONS: The CIN3 risk is confined to women with persistent type-specific HPV so partial genotyping test assays identifying HPV16/18 as a minimum are essential for efficient risk stratification. Immediate referral to colposcopy for HPV+ women with borderline or low-grade cytology and referral after a year if still HPV+ with normal cytology may be unnecessary. Low-grade lesions can safely be retested to identify those with persistent HPV. Recall intervals of 1 year for HPV16/18 and 2 years for other high-risk HPVs are justified for women with normal cytology and might also be considered for women with borderline/low-grade cytology. The minimal risk of invasive cancer that has progressed beyond stage 1A must be weighed against the advantages for patients and the NHS of reducing the number of referrals to colposcopy. TWEETABLE ABSTRACT: Cervical screening would be better for women and cheaper for the NHS if women with HPV and normal to low-grade cytology were retested after a year or two when many infections will have cleared.


Asunto(s)
Neoplasia Intraepitelial Cervical/diagnóstico , Infecciones por Papillomavirus/diagnóstico , Triaje , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Distribución por Edad , Anciano , Neoplasia Intraepitelial Cervical/epidemiología , Neoplasia Intraepitelial Cervical/virología , Detección Precóz del Cáncer , Inglaterra/epidemiología , Femenino , Estudios de Seguimiento , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/epidemiología , Factores de Riesgo , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Adulto Joven
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