Background Vigilant management of women with high-risk human papillomavirus (hrHPV) is necessary in cancer screening programs. To this end, we evaluated the performance of S5 (targeting DNA methylation in HPV16, HPV18, HPV31, HPV33, and human gene EPB41L3) to predict cervical intraepithelial neoplasia grade 2 or higher (CIN2+) in a sample of hrHPV-infected women referred to colposcopy in the FRIDA Study, a large screening trial in Mexico. A nested case-control sample with women referred to colposcopy either by atypical squamous cells of undetermined significance or higher (ASCUS+) in cytology and/or positive for HPV types 16 or 18 was tested by S5. Seventy-nine cases of CIN2+ were age-matched to 237 controls without a diagnosis of CIN2+ (<CIN2). DNA from exfoliated cervical cells was bisulfite converted and PCR amplified for S5 targets, and methylation was quantified at specific cytosines by pyrosequencing. Results The S5 classifier separated women with CIN2+ from <CIN2 with a highly significant area under the curve (AUC) of 0.75 (95% CI 0.69–0.82), while AUC for CIN3+ was 0.81 (95% CI 0.74–0.89). To optimize sensitivity and specificity for Mexico, an alternative S5 cutoff of 3.7 was implemented to account for overall higher methylation seen in our already triaged women. All three invasive cancers were detected by methylation or HPV16/18 but none by cytology. Sensitivity of S5 for CIN2+ was 62% (95% CI 50.4–72.7%), specificity was 73% (95% CI 66.9–78.5%), and adjusted PPV was 15.1% (95% CI 12.0–18.3%). In contrast, the crude sensitivity of HPV16/18 detection and cytology were 63.3% (95% CI 51.7–73.9%) and 57.0% (95% CI 45.3–68.1%) respectively; specificity was 29.1% (95% CI 23.4–35.3%) and 62.4% (95% CI 55.9–68.6%) respectively, while adjusted PPV was 6.4% (95% CI 4.9–8.1%) and 10.5% (95% CI 8.0–13.1%), respectively. Methylation testing could reduce colposcopy referrals by 30 to 50% with virtually no loss of sensitivity for CIN2+ and CIN3+. Conclusions S5 testing on hrHPV-positive women significantly increased diagnostic information compared to triage by HPV16/18 plus cytology and appears to have clinical utility as an additional test to substantially lessen burdens on colposcopy. Trial registration The FRIDA Study is registered in ClinicalTrials.gov, number NCT02510027.
Background: From the start of the COVID-19 pandemic, new SARS-CoV-2 variants have emerged that potentially affect transmissibility, severity, and immune evasion in infected individuals. In the present systematic review, the impact of different SARS-CoV-2 variants on clinical outcomes is analyzed. Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020. Two databases (PubMed and ScienceDirect) were searched for original articles published from 1 January 2020 to 23 November 2021. The articles that met the selection criteria were appraised according to the Newcastle–Ottawa Quality Assessment Scale. Results: Thirty-three articles were included, involving a total of 253,209 patients and 188,944 partial or complete SARS-CoV-2 sequences. The most reported SARS-CoV-2 variants showed changes in the spike protein, N protein, RdRp and NSP3. In 28 scenarios, SARS-CoV-2 variants were found to be associated with a mild to severe or even fatal clinical outcome, 15 articles reported such association to be statistically significant. Adjustments in eight of them were made for age, sex and other covariates. Conclusions: SARS-CoV-2 variants can potentially have an impact on clinical outcomes; future studies focused on this topic should consider several covariates that influence the clinical course of the disease.
Objective. This paper describes the study design and baseline characteristics of the study population, including the first 30 829 women who enrolled in the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA Study). This is a large population based study that is evaluating the performance and cost-effectiveness of different triage strategies for high-risk HPV (hrHPV) positive women in Mexico. Materials and methods. The target population is more than 100 000 women aged 30 to 64 years who attend the Cervical Cancer Screening Program in 100 health centers in the state of Tlaxcala, Mexico. Since August 2013, all women in the region have been invited to ResumenObjetivo.
Una de las habilidades que más requiere ser fortalecida en el área médica es la difusión de conocimiento, por tal motivo, es necesario brindar elementos que promuevan la capacitación en redacción científica. Identificar cuáles son los problemas más comunes al redactar artículos médicos originales para su publicación proporcionará recursos útiles que contribuyan a la generación de conocimiento. Existen diversos motivos que intervienen para que un artículo original no sea aceptado en una revista médica, entre los que destacan falta de apego a las instrucciones para autores, problemas metodológicos y de diseño, así como de estructura, sin embargo, el aspecto que más influye y pocas veces se señala, es la redacción inadecuada de los escritos de investigación, la cual se hace patente en las diferentes secciones que componen los manuscritos. Todos los factores mencionados son responsabilidad de los autores, por lo que deben ser atendidos apropiadamente. El presente escrito tiene como objetivo señalar los errores más comunes al redactar escritos médicos originales, los cuales, de ser evitados, incrementarán la posibilidad de que sus trabajos de investigación sean aceptados para su publicación.
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