Detección del virus del papiloma humano en Corrientes, Argentina: alta prevalencia de genotipo 58 y su filodinámica / Human papillomavirus detection in Corrientes, Argentina: High prevalence of type 58 and its phylodynamics

Human papillomavirus (HPV) has the highest mortality rate due to cervical cancer in Northeastern Argentina. The aim of this work was to detect and characterize HPV in samples from the Province of Corrientes, Argentina. HPV detection and typing was performed using PCR-RFLP on samples with different cervical lesions (n = 255). Seventeen viruses typified as HPV-58 were sequenced (E6 and E7 genes) and mutations were analyzed. HPV DNA was detected in 56.1 % of the cervical lesions (143/255). Twenty-two different HPV types were detected. The type most frequently found among the total number of samples and HPV-positive samples was HPV-16 (14.5 % and 25.9 %, respectively), followed by HPV-58 (8.2 %/14.7 %, respectively), which is also considered a high-risk viral type. Increased severity of the cytological status was associated with greater rates of HPV detection and, especially, with the detection of greater rates of high-risk types. In addition, the evolutionary dynamics of the alpha-9 species group and HPV-58 was studied. All HPV-58 viruses reported in this work belonged to lineage A, sublineage A2. The phylodynamic analysis indicated that diversification of main groups within lineage A might have accompanied or preceded human migrations across the globe. Given that the most prevalent viruses found belonged to high-risk HPV types, some concerns might arise about the extent of cross protection of the vaccines against the types not included in their design.

El virus del papiloma humano (Human papillomavirus [HPV]) tiene la mayor tasa de mortalidad por cáncer de cuello uterino en el noreste de Argentina. El objetivo de este trabajo fue detectar y caracterizar el HPV en muestras de la provincia de Corrientes, Argentina. La detección y la tipificación se realizó mediante PCR-RFLP en muestras con diferentes lesiones cervicales (n=255). Se secuenciaron 17 virus tipificados como HPV-58 (genes E6 y E7) y se analizaron sus mutaciones. Además, se estudió la dinámica evolutiva de los virus del grupo alfa-9 y, en particular, del HPV-58. Se detectó ADN viral en el 56,1% de las lesiones cervicales (143/255) y se detectaron 22 tipos del HPV. El tipo encontrado con mayor frecuencia entre el total de muestras y entre las HPV-positivas fue el HPV-16 (14,5%/25,9%, respectivamente), seguido por el HPV-58 (8,2%/14,7%, respectivamente), también considerado como de alto riesgo. El aumento de la gravedad de las lesiones se asoció a mayores tasas de detección del HPV y, en especial, con mayores tasas de detección de tipos de alto riesgo. Todos los HPV-58 encontrados pertenecieron al linaje A, sublinaje A2. El análisis filodinámico indicó que la diversificación de los grupos principales dentro del linaje A podría haber acompañado o precedido las migraciones humanas en todo el mundo. Dado que los virus más prevalentes pertenecieron a los tipos del HPV de alto riesgo, podrían surgir interrogantes sobre el alcance de la protección cruzada de las vacunas contra los tipos no incluidos en su diseño

Preliminary study on change of immunologic factors within cervical microenvironment infected with HPV 16, 58 and integrated state of virus in cervical cells / 中国免疫学杂志

Objective:To investigate the relationship between changes of the concentration of IL -12,IL-4,IFN-γwithin cervical local immune microenvironment and cervix infected with HPV 16,58,to understand the prevalence of physical status of HPV 16/58 DNA into the host genome in cervical lesions of different grades and to detect the relation between the integrated state of virus and the progress of cervical lesions.Methods: Detecting 89 cases of cervicovaginal lavage fluid and 140 cytological specimens of the cervix which from patients having had HPV-DNA genotyping assays and coming from the Affiliated Tumor Hospital of Guangxi Medical University from 2012.8 to 2013.5.89 cases of cervicovaginal lavage fluid were divided into 58 cases of HPV16 (+) and 31 cases of HPV58(+).Cytokines IL-12, IL-4, IFN-γin the cervical microenvironment were detected by ELISA assay.140 cases of cervical exfoliated cells were divided into 106 cases of HPV16(+) and 34 cases of HPV58(+).Using qRT-PCR to quantify the copy number of E2 and E6 genes and analyze the physical status of HPV 16/58 DNA according to E2/E6.Results:①The level of IL-4 in HPV16(+) was significantly higher than that in HPV58(+)(P<0.05).The levels of IL-12 and IFN-γwere lower than that in HPV58(+)(P<0.05).②Significant differences of DNA state were found between the groups of HPV 16(+) and HPV58(+)(P<0.05)and the rate of HPV16 DNA integration was significantly larger than that of HPV 58 DNA.Conclusion:The infection of HPV16 and HPV58 not only can lead to reduction of IL-12,IFN-γand increasing of IL-4 in cervical local immune microenvironment but also lead to viral integration in cervical cells,resulting in cervical lesions and cervical cancer through the internal and external changes in cervical cells .HPV16 is more likely to cause cervical cancer tissue than 58.

Distribution of Human Papillomavirus 52 and 58 Genotypes, and Their Expression of p16 and p53 in Cervical Neoplasia

BACKGROUND: This study investigates the prevalence of human papillomavirus (HPV) 52 and 58 genotypes among women residing in Busan, and the expression of p16 and p53 proteins in cervical neoplasia with HPV 52 and 58 infections. METHODS: A total of three hundred fifteen cases were analyzed using the HPV DNA chip test for HPV genotypes, and of these, we retrospectively examined p16 and p53 expression in 62 cases of cervical tissues infected with HPV 52 and 58 using immunohistochemistry. RESULTS: HPV 52 and 58 genotypes were identified in 62 (54.9%) out of 113 high-risk, HPV-infected cases. Of the cases examined, there were 19 single HPV 52 infections (16.8%), 23 single HPV 58 infections (20.4%), 4 multiple HPV 52 infections (3.5%), and 16 multiple HPV-58 infections (14.2%). Immunoreactivity of p16 and p53 was observed in 41 (66.1%) and 23 (37.1%) of the 62 cases of cervical neoplasia infected with HPV 52 and 58 genotypes, respectively. CONCLUSIONS: This study demonstrates a high prevalence of HPV 52 and 58 genotypes, in addition to HPV 16, among high-risk strains of cervical neoplasia in Korea. These findings suggest that development of more vaccines would be beneficial for the prevention of the various HPV genotypes.

High prevalence and low E6 genetic variability of human papillomavirus 58 in women with cervical cancer and precursor lesions in Southeast Mexico

Infection with some genotypes of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer (CC). Throughout the world, HPV type 58 prevalence varies from one region to another; it is higher in women from certain countries in Asia and Latin America, such as China and Mexico. Although intratypic variants have been reported on a few occasions, our knowledge about HPV 58 genetic variation remains limited. Therefore, this work aims to (i) determine the prevalence of HPV type 58 amongst Mexican women with invasive CC or precursor lesions and (ii) identify HPV 58 sequence variants. One hundred and forty five colposcopy clinic patients were studied. Genotyping of HPV 16, 18 and 58 was determined by specific nested PCR and HPV 58 variants were detected by direct sequencing. The general prevalence of HPV was 51.7 percent (75/145). HPV 16 was found in 30.6 percent (23/75) and HPV 58 in 24 percent (18/75) of the patients. HPV 18 was not identified in patients with cervical intraepithelial neoplasia (CIN) grade I; it was only found in those with CIN II, with a prevalence of 6.8 percent (3/44). In patients with CC, the prevalence of HPV 16 and 58 was 78.9 percent. Regarding HPV 58 variants, 94.4 percent of the HPV 58 sequences were identical to the prototype strain, whereas one sample showed changes at a single nucleotide. This study demonstrates a high prevalence of HPV 58 and a low genetic variability of E6 sequences amongst Mexican colposcopy patients.

Expression of the p16(INK4a) and Ki-67 in relation to the grade of cervical intraepithelial neoplasia and high-risk human papillomavirus infection / 부인종양

OBJECTIVE: The purposes of this study were to evaluate the expression of p16(INK4a) (referred as to p16) and Ki-67 in cervical intraepithelial neoplasia (CIN), and the correlation between high-risk human papillomavirus (HPV) infection and the above biomarkers. METHODS: We analyzed 31 patients who were diagnosed with CIN at Kwandong University Myongji Hospital from October 2006 to September 2007. CIN specimens (CIN1, 12; CIN2, 6; CIN3, 13) were obtained by colposcopy-directed biopsy (CDB) or loop electrical excision procedure (LEEP). The expressions of p16 and Ki-67 were evaluated by immunohistochemical methods with antibodies to p16 and Ki67. The immunohistochemical staining results were classified into four grades: 0, 1, 2 and 3. HPV genotyping or Hybrid Capture-II test was used to detect high-risk HPV. RESULTS: The expression of p16 (p<0.001) and Ki-67 (p=0.003) were positively associated with CIN grade. p16 expressions increased significantly with high-risk HPV infection (p=0.014), especially HPV type 16 and 58. Ki-67 expression was not related with high-risk HPV. There was positive correlation between the expression of the p16 and Ki-67 (p=0.007). CONCLUSION: CIN grade were positively related to the expression of p16 and Ki-67. p16 expressions of high-risk HPV specimens significantly increased more than Ki-67. Therefore, in the diagnosis of CIN and high-risk HPV infection, p16 can be a useful biomarker.