Clinical significance of human papillomavirus genotyping

Choi, Youn Jin; Park, Jong Sup

doi:10.3802/jgo.2016.27.e21

Cited by 93 publications

(82 citation statements)

References 71 publications

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“…Los virus del papiloma humano de alto riesgo (VPH-AR) han sido identificados como agentes causales de cáncer de cuello uterino (Bosch et al, 1995;Walboomers et al, 1999;Zur Hausen, 2002;Schiffman et al, 2016), la detección de VPH-AR aunque es más sensible que la citología para detectar lesiones pre malignas tiene un valor predictivo bajo dado que la mayoría de infecciones son transitorias y solo una fracción pequeña de las mujeres positivas para ADN de virus oncogénicos desarrolla cáncer de cuello uterino (Liaw et al, 2001;Arbyn et al, 2006;Cuzick et al, 2006;Bansal et al, 2008;Choi et al, 2016). Se requiere un test que permita distinguir objetivamente las infecciones transitorias que no van más allá de causar una lesión de bajo grado de las asociadas a transformación oncogénica y mayor riesgo de desarrollar lesiones de alto grado y cáncer cervical.…”

Section: Introductionunclassified

Integración, carga viral y niveles de ARN mensajero de E2 de VPH 16 en la progresión de lesiones intraepiteliales cervicales

Trujillo¹,

Sánchez²,

Bravo³

2018

Acta biol. Colomb.

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RESUMENEntre las lesiones intraepiteliales escamosas cervicales (LIE) es importante distinguir aquellas asociadas con mayor riesgo de cáncer de cuello uterino. El objetivo de este trabajo fue evaluar si los niveles de expresión de E2 del VPH16 en mujeres con LIE y con evidencia de integración viral se asocian con el grado de la lesión. Se analizaron 109 cepillados cervicales positivos para VPH 16 provenientes de 19 mujeres sin LIE, 45 mujeres con LIE de bajo grado (LIEBG) y 45 mujeres con LIE de alto grado (LIEAG). Se cuantificó el número de copias de ARNm de E2 y de los genes E2 y E6 mediante PCR en tiempo real para determinar la carga viral (E6) y la proporción E2/E6 para evaluar la integración viral. Se encontraron frecuencias similares de expresión de E2 en LEIBG y LEIAG 15/45 (33 %), la frecuencia en mujeres sin lesión fue menor 3/19 (15,8 %), todos los casos en los que se observó expresión del gen E2 tenían mezcla de ADN viral episomal e integrado. La carga viral aumentó significativamente a mayor grado de la lesión (p=0,049), mientras que la proporción E2/E6 disminuyó (p=0,049). El análisis ROC mostró una baja capacidad de los tres parámetros virales para distinguir entre lesiones de bajo y alto grado. En conclusión, aunque las lesiones con presencia de ADN viral mixto e integrado y expresión de E2 podrían estar en menor riesgo de progresión, y la carga viral y la integración se relacionaron con mayor gravedad de la lesión, su valor clínico como biomarcadores de LEIAG es limitado.Palabras clave: carga viral, integración viral, lesión intraepitelial escamosa de alto grado, lesión intraepitelial escamosa de bajo grado, reacción en cadena de la polimerasa en tiempo real, virus del Papiloma Humano tipo 16. ABSTRACTIt is important to distinguish among squamous intraepithelial lesions (SIL) those associated with increased risk cervical cancer. Our aim was to evaluate if the expression level of gen E2 in women with SIL and evidence of viral integration is associated to the grade of lesion. Cervical scrapes HPV16 positive from 19 women with normal histology, 45 women with low-grade SIL (LSIL) and 45 women with high-grade SIL (HSIL) were analyzed. Real-time PCR was used to quantify the mRNA of E2 and E2 and E6 genes to calculate viral load (E6) and the ratio E2/E6 to assess viral integration. Similar frequencies of E2 expression were found in LSIL and HSIL15/45 (33 %), the frequency in women without SIL was lower 3/19 (15.8 %), and all cases with E2 gene expression had mixed episomal and integrated viral DNA. The viral load increased significantly with the grade of SIL (p= 0.049), while E2/E6 ratio decreased (p=0.049). The ROC analysis showed low capacity of the three viral parameters analyzed to distinguish between low and high grade SIL. In conclusion although SIL with mixed and integrated viral DNA with E2 expression could be at lower risk of progression, and viral load and integration were associated with higher severity of the lesion, its clinical value as biomarkers of HSIL is limited.

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Section: Introductionunclassified

Integración, carga viral y niveles de ARN mensajero de E2 de VPH 16 en la progresión de lesiones intraepiteliales cervicales

Trujillo¹,

Sánchez²,

Bravo³

2018

Acta biol. Colomb.

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“…It is clear that persistent infection with a high -risk HPV genotype is known to be a major carcinogenic factor, however, various high -risk HPV genotypes have different carcinogenic potentials (8). Therefore, finding out the genotype -specific features of HPV infection would facilitate the expanding of better strategies to prevent and manage cervical cancer (9).…”

Section: Introductionmentioning

confidence: 99%

The Most Frequent HPV Genotypes in Women with Cervical Cancer in Southwest of Iran

et al. 2018

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Background: Cervical cancer ranked as the most common cancer of women in developing countries. Human Papillomaviruses (HPVs) belongs to the Papillomaviridea family, which is able to infect humans. Some HPV types are the causes of getting cervix cancer and it is clear that persistent infection, with a high -risk HPV genotypes, is known to be a major carcinogenic factor. Objectives: Determining the HPV genotypes distribution in women with cervical cancer in Khuzestan province, which is located in the southwest of Iran, to help design better preventive and also therapeutic strategies for promoting women health. Methods: A total of 75 archival cervical carcinoma tissue samples were studied for the presence of HPV DNA and determination of the genotypes by PCR and Sequencing. Genomic DNA was extracted from the FFPE cervical tissues and then subjected for the PCR based amplification with subsequent direct sequencing of the HPV positive PCR products. Results: The mean age of patients was 56. There were 42 samples with HPV DNA by using GP5+ and GP6+ primers. The result of HPV genotyping have been distinguished as follow: 33 samples as HPV-16, 4 samples as HPV-18, 1 sample for each HPV-54, 56 and 58 genotypes, and 2 samples remained unknown. Conclusions: Detecting HPV genotypes absolutely shed light on guidelines cervical cancer screening and vaccination policy in our country and in other developing countries. Collectively, our results suggest that HPV-16 is the frequent high -risk HPV type in our geographical area. HPV genotype testing, as a primary screening tool, plays an important role in cervical cancer prevention and therefore, it is a strongly recommended vaccination against HPV, especially for high school girls be included in the national immunization program.

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“…Epidemiological studies show that human papillomavirus (HPV) infection, in particular HPV16, is relevant in the onset of cervical cancer (2). However, an increasing body of evidence has indicated that the occurrence of cervical cancer is a result of the combined action of multiple factors, since the incidence of HPV infection in women of childbearing age is higher, but the incidence of cervical cancer is lower among these patients (3). Therefore, HPV infection is not the only factor involved in the development of cervical cancer (4,5).…”

Section: Introductionmentioning

confidence: 99%

Low folate levels are associated with methylation-mediated transcriptional repression of miR-203 and miR-375 during cervical carcinogenesis

et al. 2016

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Abstract. The aim of the present study was to investigate the correlation between a lack of folic acid and the abnormal expression of microRNA (miR)-203 and miR-375 in cervical cancer. In total, 60 tissue samples of cervical intraepithelial neoplasia (CIN) or stage IA-IIA cervical cancer (study group), and 30 samples without soluble interleukin or malignancy (control group) were examined. The expression of miR-203 and miR-375 was detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and the difference in expression levels was quantified using the 2 -ΔΔCq method. In addition, CaSki cervical cancer cells were cultured in vitro and treated with various concentrations of folic acid. The DNA methylation states of miR-203 and miR-375 were subsequently detected by methylation-specific PCR, and the expression levels were evaluated using RT-PCR. miR-203 and miR-375 were significantly downregulated in CIN and cervical cancer tissues, compared with the control group. There was a marked difference in terms of the expression levels of miR-375 between the two groups (P<0.05). In CaSki cells, as the concentration of folic acid increased, the positive rate of DNA methylation of miR-203 and miR-375 decreased, while the expression levels of miR-203 and miR-375 demonstrated a gradual increase, which indicated that the latter two parameters were negatively correlated (P<0.05). Compared with normal cervical tissue, the expression levels of miR-203 and miR-375 were downregulated in CIN and cervical cancer. Methylation of these two miRs was apparent in CaSki cells, and was associated with a lack of folic acid. Therefore, reduced levels of folic acid, leading to increased methylation of miR-203 and miR-375, may be significant events during cervical carcinogenesis.

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Clinical significance of human papillomavirus genotyping

Cited by 93 publications

References 71 publications

Integración, carga viral y niveles de ARN mensajero de E2 de VPH 16 en la progresión de lesiones intraepiteliales cervicales

Integración, carga viral y niveles de ARN mensajero de E2 de VPH 16 en la progresión de lesiones intraepiteliales cervicales

The Most Frequent HPV Genotypes in Women with Cervical Cancer in Southwest of Iran

Low folate levels are associated with methylation-mediated transcriptional repression of miR-203 and miR-375 during cervical carcinogenesis

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