ABSTRACT
OBJECTIVES: The aim was to evaluate the cross-sectional and long-term triage performance of FAM19A4/miR124-2 methylation analysis in human papillomavirus (HPV)-based cervical screening. METHODS: We conducted a post hoc analysis within a Dutch population-based HPV-positive study cohort of women aged 30-60 years (n = 979). Cross-sectional cervical intraepithelial neoplasia (CIN) 3+ sensitivity, specificity, positive predictive value and negative predictive value as well as cumulative CIN3+ or cervical cancer risks after 9 and 14 years were compared for three baseline triage strategies: (1) cytology, (2) FAM19A4/miR124-2 methylation analysis and (3) combined FAM19A4/miR124-2 methylation with cytology. RESULTS: CIN3+ sensitivity of FAM19A4/miR124-2 methylation analysis was similar to that of cytology (71.3% vs 76.0%, ratio 0.94, 95% CI 0.84 to 1.05), at a lower specificity (78.3% vs 87.0%, ratio 0.90, 95% CI 0.86 to 0.94). Combining FAM19A4/miR124-2 methylation analysis with cytology resulted in a CIN3+ sensitivity of 84.6% (95% CI 78.3 to 90.8) at a specificity of 69.6% (95% CI 66.5 to 72.7). Similar 9- and 14-year CIN3+ risks for baseline cytology-negative women and baseline FAM19A4/miR124-2 methylation-negative women were observed, with risk differences of -0.42% (95% CI -2.1 to 1.4) and -0.07% (95% CI -1.9 to 1.9), respectively. The 14-year cumulative cervical cancer incidence was significantly lower for methylation-negative women compared to cytology-negative women (risk difference 0.98%, 95% CI 0.26 to 2.0). DISCUSSION: FAM19A4/miR124-2 methylation analysis has a good triage performance on baseline screening samples, with a cross-sectional CIN3+ sensitivity and long-term triage-negative CIN3+ risk equalling cytology triage. Therefore, FAM19A4/miR124-2 methylation analysis appears to be a good and objective alternative to cytology in triage scenarios in HPV-based cervical screening.
Subject(s)
Cytokines/genetics , Papillomavirus Infections/diagnosis , Triage/methods , Adult , Biomarkers, Tumor/genetics , Cross-Sectional Studies , DNA Methylation , Early Detection of Cancer , Female , Humans , Longitudinal Studies , Mass Screening , MicroRNAs/genetics , Middle Aged , Netherlands/epidemiology , Papillomaviridae , Papillomavirus Infections/genetics , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/genetics , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Dysplasia/geneticsABSTRACT
OBJECTIVE: We investigated whether psychopathology in HIV-positive patients was associated with more negative fundamental assumptions than in healthy controls. In addition, we explored whether psychopathology and negative fundamental assumptions in HIV-positive patients were associated with lower CD4 T-lymphocyte counts. METHOD: Self-rating questionnaires to assess depressive symptoms, posttraumatic stress symptoms, alcohol abuse, general psychopathology and fundamental assumptions, were completed by 123 HIV-positive patients and 84 uninfected clinic attendees at three primary health care clinics in the Western Cape, South Africa. CD4 T-lymphocyte counts were obtained from chart records. RESULTS: HIV-positive patients reported more depressive and posttraumatic symptoms than uninfected individuals. However when controlling for socio-economic status, the number of traumatic events experienced and other potential confounds, no differences remained. Fundamental assumptions (FA) were mainly positive in both HIV-positive patients and controls and no correlations were found between fundamental assumptions, psychiatric symptoms and CD4 levels. However, in infected patients FA and psychopathology were negatively associated with all participants scoring in the positive range of the FA scale. CONCLUSION: The positive scores on the FA scale indicate that positive assumptions are related to less psychopathology. Longitudinal studies investigating the association between the valence of fundamental assumptions and HIV morbidity are needed.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/pathology , Depressive Disorder/diagnosis , HIV Seropositivity/psychology , Stress Disorders, Post-Traumatic/diagnosis , Adolescent , Adult , Aged , Depressive Disorder/immunology , Female , HIV Seropositivity/immunology , HIV Seropositivity/pathology , Humans , Life Change Events , Male , Middle Aged , Neuropsychological Tests , Socioeconomic Factors , South Africa , Stress Disorders, Post-Traumatic/immunology , Stress Disorders, Post-Traumatic/pathology , Surveys and Questionnaires , Young AdultABSTRACT
Objective: We investigated whether psychopathology in HIV-positive patients was associated with more negative fundamental assumptions than in healthy controls. In addition; we explored whether psychopathology and negative fundamental assumptions in HIV-positive patients were associated with lower CD4 T-lymphocyte counts. Method: Self-rating questionnaires to assess depressive symptoms; posttraumatic stress symptoms; alcohol abuse; general psychopathology and fundamental assumptions; were completed by 123 HIV-positive patients and 84 uninfected clinic attendees at three primary health care clinics in the Western Cape; South Africa. CD4 T-lymphocyte counts were obtained from chart records. Results: HIV-positive patients reported more depressive and posttraumatic symptoms than uninfected individuals. However when controlling for socio-economic status; the number of traumatic events experienced and other potential confounds; no differences remained. Fundamental assumptions (FA) were mainly positive in both HIV-positive patients and controls and no correlations were found between fundamental assumptions; psychiatric symptoms and CD4 levels. However; in infected patients FA and psychopathology were negatively associated with all participants scoring in the positive range of the FA scale. Conclusion: The positive scores on the FA scale indicate that positive assumptions are related to less psychopathology. Longitudinal studies investigating the association between the valence of fundamental assumptions and HIV morbidity are needed
