New perspectives on screening and early detection of endometrial cancer

Costas, Laura; Frias-Gomez, Jon; Guardiola, Magdalena; Benavente, Yolanda; Pineda, Marta; Pavón, Miquel Ángel; Martínez, José Manuel; Climent, Maite; Barahona, Marc; Canet, Júlia; Paytubi, Sònia; Salinas, Mónica; Palomero, Luís; Bianchi, Ilaria; Reventós, Jaume; Capellà, Gabriel; Díaz, Mireia; Vidal, August; Piulats, Josep María; Aytés, Álvaro; Ponce, Jordi; Brunet, Joan; Bosch, F. Xavier; Matías‐Guiu, Xavier; Alemany, Laia; Sanjosé, Sílvia de; Team, Screenwide

doi:10.1002/ijc.32514

Cited by 62 publications

(70 citation statements)

References 116 publications

(239 reference statements)

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“…Most endometrial cancers are diagnosed in postmenopausal women, in whom Pap tests are no longer routinely performed. However, molecular analyses of Pap tests could offer a benefit in the early detection of endometrial cancer, since they are better tolerated by women than aspirate‐based diagnosis 14 . Similarly, these new molecular tests in Pap tests and other minimally invasive sampling methods could also improve current preventive strategies among asymptomatic, high‐risk populations 14 …”

Section: Introductionmentioning

confidence: 99%

Sensitivity of cervico‐vaginal cytology in endometrial carcinoma: A systematic review and meta‐analysis

Frias-Gomez

Benavente

Ponce

et al. 2020

Cancer Cytopathology

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Cervico‐vaginal cytology is primarily a cervical cancer screening test. The anatomical continuity of the uterine cavity with the cervix makes the Papanicolaou (Pap) test accessible to evaluate signs of disease shed from the endometrium. Our aim was to determine the sensitivity of routine Pap test in endometrial carcinoma detection and its relationship with clinico‐pathologic factors. We performed a systematic review of studies reporting Pap test results prior to diagnosis of or surgery for endometrial carcinoma between 1990 and 2018 in PubMed or Web of Science. Two independent reviewers extracted data and assessed study quality using an adapted Newcastle‐Ottawa Quality Assessment Scale and Quality Assessment of Diagnostic Accuracy Studies tool. We identified 45 studies including a total of 6599 women with endometrial cancer. Abnormal Pap test results prior to diagnosis of or surgery for endometrial carcinoma were observed in 45% (95% CI, 40%‐50%) of study participants. This percentage was significantly higher among those of non‐endometrioid histology compared with endometrioid subtypes (77% [95% CI, 66%‐87%] vs 44% [95% CI, 34%‐53%], respectively; P heterogeneity <.001). Several clinico‐pathologic factors were related to a higher percentage of abnormal Pap test results, including high‐stage, myometrial invasion >50%, high histological grade, positive peritoneal cytology, presence of lymph node metastasis, cervical involvement, and lymphovascular invasion (P heterogeneity <.05 for all variables). Routine cervical cytology can detect endometrial cancer in almost half of patients, whereas sensitivity is higher among individuals with non‐endometrioid histology or more advanced cancers. This review summarizes the current clinical and prognostic value of cervical cytology in endometrial carcinoma. Recent technological developments using molecular biomarkers may improve accuracy for early cancer detection.

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Section: Introductionmentioning

confidence: 99%

Sensitivity of cervico‐vaginal cytology in endometrial carcinoma: A systematic review and meta‐analysis

Frias-Gomez

Benavente

Ponce

et al. 2020

Cancer Cytopathology

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“…Metabolites for EC detection may be identified in endometrial tissue, brush and lavage specimens, blood samples (serum/plasma) and urine ( Figure 1) [45]. Direct sampling of the endometrial cavity by aspiration, brushing and lavage has great potential to yield EC-relevant biomarkers given its close proximity to the tumour.…”

Section: Metabolomics and Ec Biomarker Discoverymentioning

confidence: 99%

“…Uterine-shed metabolites may contaminate voided urine samples, particularly in symptomatic women, due to the close proximity of the urethra and vagina, but this may be an unreliable source of biomarkers if uterine shedding is episodic and inconsistent, as might be expected in early stage disease [13]. The anatomical continuity between the upper and lower female genital tracts may provide an opportunity for the collection of uterine tissue-derived EC metabolites using minimally invasive strategies such as vaginal swabs, tampons and cervicovaginal sampling devices [45]. Further studies exploring this possibility are urgently needed.…”

Section: Metabolomics and Ec Biomarker Discoverymentioning

confidence: 99%

Metabolomic Biomarkers for Detection, Prognosis and Identifying Recurrence in Endometrial Cancer

et al. 2020

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Metabolic reprogramming is increasingly recognised as one of the defining hallmarks of tumorigenesis. There is compelling evidence to suggest that endometrial cancer develops and progresses in the context of profound metabolic dysfunction. Whilst the incidence of endometrial cancer continues to rise in parallel with the global epidemic of obesity, there are, as yet, no validated biomarkers that can aid risk prediction, early detection, prognostic evaluation or surveillance. Advances in high-throughput technologies have, in recent times, shown promise for biomarker discovery based on genomic, transcriptomic, proteomic and metabolomic platforms. Metabolomics, the large-scale study of metabolites, deals with the downstream products of the other omics technologies and thus best reflects the human phenotype. This review aims to provide a summary and critical synthesis of the existing literature with the ultimate goal of identifying the most promising metabolite biomarkers that can augment current endometrial cancer diagnostic, prognostic and recurrence surveillance strategies. Identified metabolites and their biochemical pathways are discussed in the context of what we know about endometrial carcinogenesis and their potential clinical utility is evaluated. Finally, we underscore the challenges inherent in metabolomic biomarker discovery and validation and provide fresh perspectives and directions for future endometrial cancer biomarker research.

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“…Despite the rising incidence of EC and proven value of early diagnosis, no screening program for EC exists [ 6 , 7 ]. In addition, if EC is suspected, invasive biopsy procedures remain necessary in routine clinical practice to detect EC in symptomatic women.…”

Section: Introductionmentioning

confidence: 99%

“…Hence, there is a need to detect EC using less invasive sampling methods, combined with the analysis of cancer-specific markers [ 6 ]. One of the emerging biomarkers for early cancer detection is DNA methylation, which involves the addition of a methyl group to a cytosine-guanine dinucleotide (CpG).…”

Section: Introductionmentioning

confidence: 99%

Non-invasive detection of endometrial cancer by DNA methylation analysis in urine

et al. 2020

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Background The incidence of endometrial cancer is rising, and current diagnostics often require invasive biopsy procedures. Urine may offer an alternative sample type, which is easily accessible and allows repetitive self-sampling at home. Here, we set out to investigate the feasibility of endometrial cancer detection in urine using DNA methylation analysis. Results Urine samples of endometrial cancer patients (n = 42) and healthy controls (n = 46) were separated into three fractions (full void urine, urine sediment, and urine supernatant) and tested for three DNA methylation markers (GHSR, SST, ZIC1). Strong to very strong correlations (r = 0.77–0.92) were found amongst the different urine fractions. All DNA methylation markers showed increased methylation levels in patients as compared to controls, in all urine fractions. The highest diagnostic potential for endometrial cancer detection in urine was found in full void urine, with area under the receiver operating characteristic curve values ranging from 0.86 to 0.95. Conclusions This feasibility study demonstrates, for the first time, that DNA methylation analysis in urine could provide a non-invasive alternative for the detection of endometrial cancer. Further investigation is warranted to validate its clinical usefulness. Potential applications of this diagnostic approach include the screening of asymptomatic women, triaging women with postmenopausal bleeding symptoms, and monitoring women with increased endometrial cancer risk.

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New perspectives on screening and early detection of endometrial cancer

Cited by 62 publications

References 116 publications

Sensitivity of cervico‐vaginal cytology in endometrial carcinoma: A systematic review and meta‐analysis

Sensitivity of cervico‐vaginal cytology in endometrial carcinoma: A systematic review and meta‐analysis

Metabolomic Biomarkers for Detection, Prognosis and Identifying Recurrence in Endometrial Cancer

Non-invasive detection of endometrial cancer by DNA methylation analysis in urine

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