Association of human papillomavirus 16 E6 variants with cervical carcinoma and precursor lesions in women from Southern Mexico

Ortíz-Ortíz, Julio; Alarcón‐Romero, Luz del Carmen; Jiménez‐López, Marco Antonio; Garzón-Barrientos, Víctor Hugo; Calleja-Macías, Itzel E.; Barrera-Saldaña, Hugo A.; Leyva‐Vázquez, Marco Antonio; Illades‐Aguiar, Berenice

doi:10.1186/s12985-015-0242-3

Cited by 32 publications

(29 citation statements)

References 44 publications

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“…The EUR-350G isolate was 1.5 times more represented than the EUR-350T isolate in this cohort of women, with stability of this ratio (EUR-350T/EUR-350G) existing for the 2012-2015 period, like in other French studies [48]. A small fraction of these lineages contained co-mutations that were previously described [49,50].…”

Section: Discussionsupporting

confidence: 74%

Relationship between E6-E7 lineage sequences, viral loads, and integration of HPV16 in women with atypical squamous cells of undetermined significance (ASCUS) pap smears

Loubatier¹,

Monte²,

Cannavo³

et al. 2018

Obstet Gynecol Rep

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HPV16 DNA associated with histologic high-grade precancer lesions (cervical intraepithelial neoplasia grade 2 or 3 [CIN2 or CIN3]) is sometimes found in women with atypical squamous cells of undetermined significance (ASCUS) Pap smears, the mildest form of cellular abnormality in a cervical smear. This study evaluated, in a population of patients with ASCUS Pap smears, the prevalence of different HPV16 lineages (or isolates) and the physical status, total viral load, and integrated viral load of HPV16 DNA in a population, stratified by HPV16 isolates (primarily either EUR-350T or EUR-350G) that was found. We demonstrated, in smears of women diagnosed with ASCUS and infected with EUR-350G HPV16 isolates (sublineage A1) that both the physical status of HPV16 and the distribution of integrated HPV16 DNA viral loads were different when compared to a population infected with EUR-350T HPV16 isolates. We showed that the mean and median percentages of HPV16 DNA were higher, and a distribution of log 10 integrated HPV16 viral load was more homogeneous in a population infected with EUR-350G HPV16 isolates than in a population infected with EUR-350T HPV16 isolates. No difference was found in terms of total HPV16 viral load between these two isolates. Here, we investigate E6-E7 sequencing as an easy technique to detect women with a greater proportion of integrated HPV genome, and we suggest an adaptation of the current protocol for monitoring women with ASCUS Pap smears.

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Section: Discussionsupporting

confidence: 74%

Relationship between E6-E7 lineage sequences, viral loads, and integration of HPV16 in women with atypical squamous cells of undetermined significance (ASCUS) pap smears

Loubatier¹,

Monte²,

Cannavo³

et al. 2018

Obstet Gynecol Rep

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“…Similar results were obtained in Slovenian patients with cervical cancer, where mainly European genomic variations of HPV16 were found and only 2/40 (5%) of the cases were associated with non-European HPV16 genomic variants -the Asian-American and African 2 branches (Vrtačnik Bokal et al, 2010). Several studies showed that non-European HPV16 genomic variants (lineage B, C, D) are associated with stronger oncogenic potential than the European line- Xi et al, 2007;Sichero et al, 2007;Schiffman et al, 2010;Freitas et al, 2014;Ortiz-Ortiz et al, 2015). Moreover, the Asian American// North American (AA/NA ) variants were linked to higher capacity of in vitro transformation of human keratinocytes (Sichero et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

HPV16 E6 polymorphism in correlation to physical state of viral genome and risk of cervical cancer in women from the south of Poland

Szostek

Zawilińska²,

Klimek³

et al. 2017

Acta Biochim Pol

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The aim of this study was to analyse the correlation between HPV16 E6 variants and the physical status of viral genome (integrated, mixed, episomal) among patients with cervical cancer (n=40) and low-grade squamous intraepithelial lesions - LSIL (n=40). The study was performed on 80 HPV16 positive samples. HPV16 E6 variants were identified using PCR and DNA sequencing. Nucleotide sequences of E6 were compared with the prototype sequence (EUR-350T). The physical state of HPV DNA was determined as the ratio of E2/E6 copy number per cell. Twelve different intratypic variants were identified as belonging to European (in 77 samples) and North-American 1 (in 3 samples) sublineages. The most prevalent non-synonymous variant was EUR-350G, which occurred with similar frequency in cervical cancer and LSIL. The frequencies of additional mutations in variants with EUR-350T or EUR-350G sequences differed significantly. For the first time, missense mutations G122A, C153T and G188A were discovered in EUR-350G variant. The integrated viral genome was predominant in women with cervical cancer. The EUR-350T prototype and EUR-350G without additional mutations variants were prevalent in cervical cancer samples with the HPV16 characterized by integrated DNA. In summary, European variants of HPV16 E6 dominated in both cancer and LSIL group. The presence of EUR-350G favoured the occurrence of additional nucleotide changes. We showed that nucleotide changes occur significantly more often in the mixed form of viral DNA and in LSIL group and that the variants without additional mutations may promote integration of HPV16 genome.

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“…The European variant lineage is further arranged into several variant sublineages [ 10 , 11 ]. Diverse HPV16 variants have in studies shown to contribute to the development of cervical cancer and precancerous lesions to different degrees [ 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

Findings of multiple HPV genotypes in cervical carcinoma are associated with poor cancer-specific survival in a Swedish cohort of cervical cancer primarily treated with radiotherapy

et al. 2018

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Cervical cancer (CC) is one of the most common cancers in women and virtually all cases of CC are a result of a persistent infection of human papillomavirus (HPV). For disease detected in early stages there is curing treatment but when diagnosed late with recurring disease and metastasis there are limited possibilities. Here we evaluate HPV impact on treatment resistance and metastatic disease progression.Prevalence and distribution of HPV genotypes and HPV16 variants in a Swedish CC patient cohort (n=209) was evaluated, as well as HPV influence on patient prognosis. Tumor samples suitable for analysis (n=204) were genotyped using two different real-time PCR methods. HPV16 variant analysis was made using pyrosequencing.Results showed that HPV prevalence in the total series was 93%. Of the HPV-positive samples, 13% contained multiple infections, typically with two high-risk HPV together. Primary cure rate for the complete series was 95%. Recurrence rate of the complete series was 28% and distant recurrences were most frequent (20%). Patients with tumors containing multiple HPV-strains and particularly HPV genotypes belonging to the alpha 7 and 9 species together had a significantly higher rate of distant tumor recurrences and worse cancer-specific survival rate.

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Association of human papillomavirus 16 E6 variants with cervical carcinoma and precursor lesions in women from Southern Mexico

Cited by 32 publications

References 44 publications

Relationship between E6-E7 lineage sequences, viral loads, and integration of HPV16 in women with atypical squamous cells of undetermined significance (ASCUS) pap smears

Relationship between E6-E7 lineage sequences, viral loads, and integration of HPV16 in women with atypical squamous cells of undetermined significance (ASCUS) pap smears

HPV16 E6 polymorphism in correlation to physical state of viral genome and risk of cervical cancer in women from the south of Poland

Findings of multiple HPV genotypes in cervical carcinoma are associated with poor cancer-specific survival in a Swedish cohort of cervical cancer primarily treated with radiotherapy

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