Comparison of Hybribio-H13 and Hybrid Capture® 2 human papillomavirus tests for detection of CIN2+ and CIN3. / Comparación de las pruebas para el virus del papiloma humano Hybribio-H13 y Hybrid Capture® 2 para la detección de NIC2+ y NIC3+

INTRODUCTION: Low-cost, accurate high-risk HPV tests are needed for cervical cancer screening in limited-resource settings. OBJECTIVE: To compare the performance of the low-cost Hybribio-H13 test with the Hybrid Capture® 2 to detect cervical intraepithelial neoplasia grade 2 or 3 (CIN2 and CIN3). MATERIALS AND METHODS: Archived baseline samples tested by the Hybrid Capture® 2 from women of the ASCUS-COL trial, aged 20 to 69 years, with biopsy-colposcopy directed diagnosis of CIN2+ (n = 143), CIN3+ (n = 51), and < CIN2 (n = 632) were blindly tested by the Hybribio-H13 test. RESULTS: The relative sensitivity of the Hybribio-H13 test versus the Hybrid Capture® 2 for detecting CIN2+ was 0.89 (90% CI = 0,80-0,98; NIT = 0,66), and for CIN3+ was 0,92 (90% CI = 0,85-0,98; NIT = 0,35). Relative specificity was 1.19 (90% CI = 1.05-1.33; NIT <0.00001). In the analysis restricted to women older than 30 years, the relative sensitivity of the Hybribio-H13 for CIN3+ was marginally below unity (ratio = 0.97; 90% CI = 0.95-0.99), and the specificity remained higher than the Hybrid Capture® 2 test. CONCLUSION: The Hybribio-H13 test was as specific as the Hybrid Capture® 2 for detecting CIN2+ or CIN3+ but less sensitive. Considering these results and the young age of the population recruited for screening because of ASCUS cytology, we suggest our results warrant the evaluation of the Hybribio-H13 for screening cervical cancer, especially in the evaluated population.

Introducción. Se necesitan pruebas para detectar genotipos de VPH de alto riesgo, precisas y de bajo costo, para la tamización del cáncer de cuello uterino en entornos de recursos limitados. Objetivo. Comparar el desempeño de la prueba de bajo costo Hybrid-H13 con la de Hybrid Capture® 2 para detectar NIC2+ y NIC3+. Materiales y métodos. Se analizaron en ciego muestras de la línea base provenientes de mujeres del estudio ASCUS-COL, entre los 20 y los 69 años, con diagnóstico dirigido por biopsia-colposcopia de NIC2+ (n = 143), NIC3 + (n = 51) y < NIC2 (n = 632) con la prueba para detección de virus de papiloma humano Hybribio-H13. Estas muestras fueron previamente evaluadas con la prueba Hybrid Capture® 2. Resultados. La sensibilidad relativa de Hybribio-13 versus la de Hybrid Capture® 2 para detectar NIC2+ fue de 0,89 (IC90%: 0,80-0,98; NIT = 0,66) y para NIC3+ fue de 0,92 (IC90%: 0,85-0,98; NIT = 0,35). La especificidad relativa fue de 1,19 (IC90%: 1,05-1,33; NIT <0,00001). En el análisis restringido a mujeres mayores de 30 años, la sensibilidad relativa de Hybribio-H13 para NIC3+ estuvo marginalmente por debajo de la unidad (proporción = 0,97; IC90%: 0,95-0,99) y la especificidad permaneció más alta que la de la prueba Hybrid Capture® 2. Conclusión. La prueba de Hybribio-H13 fue tan específica como la de Hybrid Capture® 2, pero menos sensible para detectar NIC2+ o NIC3+. Teniendo en cuenta estos resultados y la temprana edad de la población reclutada en la tamización por la presencia de ASCUS en la citología, se sugiere continuar con la evaluación de la prueba Hybribio-H13 para la detección de cáncer de cuello uterino en poblaciones con las mismas características que las de la aquí evaluada.

Comparison of Hybribio-H13 and Hybrid Capture® 2 human papillomavirus tests for detection of CIN2+ and CIN3+ / Comparación de las pruebas para el virus del papiloma humano Hybribio-H13 y Hybrid Capture® 2 para la detección de NIC2+ y NIC3+

Abstract Introduction. Low-cost, accurate high-risk HPV tests are needed for cervical cancer screening in limited-resource settings. Objective. To compare the performance of the low-cost Hybribio-H13 test with the Hybrid Capture® 2 to detect cervical intraepithelial neoplasia grade 2 or 3 (CIN2 and CIN3). Materials and methods. Archived baseline samples tested by the Hybrid Capture® 2 from women of the ASCUS-COL trial, aged 20 to 69 years, with biopsy-colposcopy directed diagnosis of CIN2+ (n = 143), CIN3+ (n = 51), and < CIN2 (n = 632) were blindly tested by the Hybribio-H13 test. Results. The relative sensitivity of the Hybribio-H13 test versus the Hybrid Capture® 2 for detecting CIN2+ was 0.89 (90% CI = 0,80-0,98; NIT = 0,66), and for CIN3+ was 0,92 (90% CI = 0,85-0,98; NIT = 0,35). Relative specificity was 1.19 (90% CI = 1.05-1.33; NIT < 0.00001). In the analysis restricted to women older than 30 years, the relative sensitivity of the Hybribio-H13 for CIN3+ was marginally below unity (ratio = 0.97; 90% CI = 0.95-0.99), and the specificity remained higher than the Hybrid Capture® 2 test. Conclusion. The Hybribio-H13 test was as specific as the Hybrid Capture® 2 for detecting CIN2+ or CIN3+ but less sensitive. Considering these results and the young age of the population recruited for screening because of ASCUS cytology, we suggest our results warrant the evaluation of the Hybribio-H13 for screening cervical cancer, especially in the evaluated population.

Resumen Introducción. Se necesitan pruebas para detectar genotipos de VPH de alto riesgo, precisas y de bajo costo, para la tamización del cáncer de cuello uterino en entornos de recursos limitados. Objetivo. Comparar el desempeño de la prueba de bajo costo Hybrid-H13 con la de Hybrid Capture® 2 para detectar NIC2+ y NIC3+. Materiales y métodos. Se analizaron en ciego muestras de la línea base provenientes de mujeres del estudio ASCUS-COL, entre los 20 y los 69 años, con diagnóstico dirigido por biopsia-colposcopia de NIC2+ (n = 143), NIC3 + (n = 51) y < NIC2 (n = 632) con la prueba para detección de virus de papiloma humano Hybribio-H13. Estas muestras fueron previamente evaluadas con la prueba Hybrid Capture® 2. Resultados. La sensibilidad relativa de Hybribio-13 versus la de Hybrid Capture® 2 para detectar NIC2+ fue de 0,89 (IC90%: 0,80-0,98; NIT = 0,66) y para NIC3+ fue de 0,92 (IC90%: 0,85-0,98; NIT = 0,35). La especificidad relativa fue de 1,19 (IC90%: 1,05-1,33; NIT < 0,00001). En el análisis restringido a mujeres mayores de 30 años, la sensibilidad relativa de Hybribio-H13 para NIC3+ estuvo marginalmente por debajo de la unidad (proporción = 0,97; IC90%: 0,95-0,99) y la especificidad permaneció más alta que la de la prueba Hybrid Capture® 2. Conclusión. La prueba de Hybribio-H13 fue tan específica como la de Hybrid Capture® 2, pero menos sensible para detectar NIC2+ o NIC3+. Teniendo en cuenta estos resultados y la temprana edad de la población reclutada en la tamización por la presencia de ASCUS en la citología, se sugiere continuar con la evaluación de la prueba Hybribio-H13 para la detección de cáncer de cuello uterino en poblaciones con las mismas características que las de la aquí evaluada.

Aflatoxin levels and prevalence of TP53 aflatoxin-mutations in hepatocellular carcinomas in Mexico.

OBJECTIVE: To determine the exposure to aflatoxin B1 (AFB1) in southern Mexico and the presence of the aflatoxin signature mutation in hepatocellular carcinoma (HCC) tissue from patients from a cancer referral center. MATERIALS AND METHODS: We estimated the prevalence and distribution of AFB1 in a representative sample of 100 women and men from Chiapas using the National Health and Nutrition Survey 2018-19. We also examined the presence of the aflatoxin signature mutation in codon 249 (R249S), and other relevant mutations of the TP53 gene in HCC tissue blocks from 24 women and 26 men treated in a national cancer referral center. RESULTS: The prevalence of AFB1 in serum samples was 85.5% (95%CI 72.1-93.1) and the median AFB1 was 0.117 pg/µL (IQR, 0.050-0.350). We detected TP53 R249S in three of the 50 HCCs (6.0%) and observed four other G>T transversions potentially induced by AFB1. CONCLUSION: Our analysis provides evidence that AFB1 may have a relevant role on HCC etiology in Mexico.

Aflatoxin levels and prevalence of TP53 aflatoxin-mutations in hepatocellular carcinomas in Mexico / Niveles de aflatoxina y prevalencia de mutaciones del gen TP53 por aflatoxina en carcinoma hepatocelular en México

Abstract: Objective: To determine the exposure to aflatoxin B1 (AFB1) in southern Mexico and the presence of the aflatoxin signature mutation in hepatocellular carcinoma (HCC) tissue from patients from a cancer referral center. Materials and methods: We estimated the prevalence and distribution of AFB1 in a representative sample of 100 women and men from Chiapas using the National Health and Nutrition Survey 2018-19. We also examined the presence of the aflatoxin signature mutation in codon 249 (R249S), and other relevant mutations of the TP53 gene in HCC tissue blocks from 24 women and 26 men treated in a national cancer referral center. Results: The prevalence of AFB1 in serum samples was 85.5% (95%CI 72.1-93.1) and the median AFB1 was 0.117 pg/µL (IQR, 0.050-0.350). We detected TP53 R249S in three of the 50 HCCs (6.0%) and observed four other G>T transversions potentially induced by AFB1. Conclusion: Our analysis provides evidence that AFB1 may have a relevant role on HCC etiology in Mexico.

Resumen: Objetivo: Determinar la exposición a aflatoxina_B1 (AFB1) en el sur de México y la presencia de la mutación característica de AFB1 en tejido de carcinoma hepatocelular (CHC) de pacientes de un centro oncológico. Material y métodos: Se estimó la prevalencia y distribución de AFB1 en una muestra representativa de 100 mujeres y hombres de Chiapas a partir de la Encuesta Nacional de Salud y Nutrición 2018-19. También se observó la presencia de la mutación característica de AFB1 en el codón 249 (R249S), y otras mutaciones relevantes del gen TP53 en bloques de tejido de CHC de 24 mujeres y 26 hombres estudiados en un centro de referencia nacional de oncología. Resultados: La prevalencia de AFB1 en las muestras de suero fue de 85.5% (IC95% 72.1-93.1) y la mediana de la concentración 0.117 pg/µL (IQR, 0.050-0.350). Se detectó TP53 R249S en tres de 50 casos de CHC (6.0%) y se observaron cuatro transversiones G>T potencialmente inducidas por AFB1. Conclusión: El presente análisis proporciona evidencia de que la AFB1 puede tener un papel relevante en la etiología del CHC en México.

Long noncoding RNA POU6F2-AS1 regulates lung cancer aggressiveness through sponging miR-34c-5p to modulate KCNJ4 expression.

It has been extensively reported that long noncoding RNAs (lncRNAs) were closely associated with multiple malignancies. The aim of our study was to investigate the effects and mechanism of lncRNA POU6F2-AS1 in lung adenocarcinoma (LADC).The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets provided us the information of LADC clinical samples. High-regulation of POU6F2-AS1 was presented in LADC tissues compared with adjacent normal tissues, which was correlated with poor outcome of LADC patients. Functional experiments in Calu-3 and NCI-H460 cells showed that POU6F2-AS1 significantly promoted LADC cell proliferation, colony formation, invasion and migration. Moreover, through online prediction, luciferase reporter assay and Pearson's correlation analysis, we found that POU6F2-AS1 may act as a competing endogenous RNA (ceRNA) of miR-34c-5p and facilitated the expression of potassium voltage-gated channel subfamily J member 4 (KCNJ4). The promoting effect of cell aggressiveness induced by POU6F2-AS1 was enhanced by KCNJ4, whilst was abrogated due to the overexpression of miR-34c-5p. Collectively, POU6F2-AS1 might function as a ceRNA through sponging miR-34c-5p to high-regulate KCNJ4 in LADC, which indicates that POU6F2-AS1 might be a promising therapeutic target with significant prognostic value for LADC treatment.

Analysis of TP53 aflatoxin signature mutation in hepatocellular carcinomas from Guatemala: A cross-sectional study (2016-2017).

BACKGROUND AND AIMS: Guatemala has the highest incidence of hepatocellular carcinoma (HCC) in the Western hemisphere. The major risk factors in Guatemala are not well characterized, but the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) appears to be low, while the prevalence of aflatoxin (AFB1) exposure appears to be high. To examine whether AFB1 may contribute to the elevated incidence of HCC in Guatemala, this study examined the frequency of the AFB1-signature mutation in the TP53 gene (R249S) as well as other somatic mutations. In addition, we assessed whether the frequency of the TP53 mutation differed by sex. METHODS: Formalin-fixed, paraffin-embedded (FFPE) HCC tissues were obtained from three hospitals in Guatemala City between 2016 and 2017. In addition, tumor tissues preserved in RNAlater were also obtained. Sociodemographic and clinical information including HBV and HCV status were collected. Targeted sequencing of TP53 was performed in the FFPE samples, and a panel of 253 cancer-related genes was sequenced in the RNAlater samples. RESULTS: Ninety-one FFPE tissues were examined, from 52 men and 39 women. Median (IQR) age at diagnosis was 62 (51-70). Among those with known HBV and HCV status, two were HBV+ and three were HCV+. Overall, 47% of the HCCs had a TP53 mutation. The AFB1-signature R249S mutation was present in 24%. No overlap between the R249S mutation and HBV+ was observed in this cohort. Among 18 RNAlater samples examined, 44% had any TP53 mutation and 33% had the R249S mutation. Other somatic mutations were identified in known HCC driver genes. CONCLUSIONS: The presence of the TP53 R249S mutation in the samples studied suggests that AFB1 may contribute to the high incidence of HCC in Guatemala. The proportion of HBV+ tumors was low, suggesting that AFB1 may be associated with HCC in the absence of concomitant HBV infection. Further investigation of AFB1 and other risk factors for HCC in Guatemala is warranted.