Human Papillomavirus Type 16 Variants and Risk of Cervical Cancer

Hildesheim, Allan; Schiffman, Mark; Bromley, Christina; Wacholder, Sholom; Herrero, Rolando; Rodríguez, Ana Cecilia; Bratti, M. Concepción; Sherman, Mark E.; Scarpidis, Ulysses; Lin, Quan Qiu; Terai, Masonoria; Bromley, Ronald L.; Buetow, Kenneth H.; Apple, Raymond; Burk, Robert D.

doi:10.1093/jnci/93.4.315

Cited by 203 publications

(193 citation statements)

References 23 publications

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“…This nt exchange is not present in African or European genotypes. A statistically significant association was observed between non-European LCR variants containing this polymorphism and disease status in a study of women from Costa Rica (Hildesheim et al, 2001). Similar results were obtained in a Brazilian and in a north American study (Xi et al, 1997;Villa et al, 2000).…”

Section: Discussionsupporting

confidence: 80%

Variants of the long control region and the E6 oncogene in European human papillomavirus type 16 isolates: implications for cervical disease

et al. 2002

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High-risk human papillomavirus types, especially type 16, are risk factors for cervical cancer. Preliminary studies suggest that HPV16 polymorphisms in the long control region or in the E6 gene may alter the oncogenic potential of the virus. This could partially explain why some lesions progress to cancer while others do not. A systematic study combining the long control region and E6 has not been undertaken. This prompted us to investigate the long control region and the E6 in northern European women infected with human papillomavirus 16. We identified the sequence variations of both regions and investigated the long control region promoter activity among various isolates. In addition, we correlated the distribution of long control region and E6 polymorphisms with disease status. We analyzed 45 samples from Swedish and Finnish women. The long control region and the E6 gene were sequenced after polymerase chain reaction long control region fragments of six European isolates covering the majority of polymorphisms in this region were ligated into the pALuc vector and used for luciferase assays. In European HPV16 isolates, polymorphisms in the long control region are more frequent than in the E6 gene. Nevertheless, the promoter function was slightly increased in only one of the tested European long control region variants. In addition, we found a specific European E6 variant, L83V, to be enriched in high-grade lesions and cancer rather than a specific European long control region variant. The difference in oncogenicity between European HPV16 genotypes is more probably due to an altered property of the corresponding E6 proteins rather than to an altered activity of the P97 promoter.

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Section: Discussionsupporting

confidence: 80%

Variants of the long control region and the E6 oncogene in European human papillomavirus type 16 isolates: implications for cervical disease

et al. 2002

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“…HPV 16 variants, which vary by Յ2% from HPV 16 prototype nucleotide sequences, have been identified as the following six phylogenetic branches: European (E), Asian (As), Asian-American (AA), African-1 (Af-1), African-2 (Af-2), and northern American (NA) variants (18,52). Several researchers had reported correlations between specific HPV 16 variants and persistent viral infection, followed by the development of malignant lesions (3,4,16,37,43,49,50). Non-European variants were found to be associated with an excess risk of cervical cancer (37).…”

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confidence: 99%

Human Papillomavirus Type 16 Variant Analysis of E6, E7, and L1 Genes and Long Control Region in Identification of Cervical Carcinomas in Patients in Northeast China

et al. 2011

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Human papillomavirus type 16 (HPV 16) is the primary etiology of cervical cancer, which is the second most common type of cancer in women worldwide (29). HPV 16 variants, which vary by Յ2% from HPV 16 prototype nucleotide sequences, have been identified as the following six phylogenetic branches: European (E), Asian (As), Asian-American (AA), African-1 (Af-1), African-2 (Af-2), and northern American (NA) variants (18,52). Several researchers had reported correlations between specific HPV 16 variants and persistent viral infection, followed by the development of malignant lesions (3,4,16,37,43,49,50). Non-European variants were found to be associated with an excess risk of cervical cancer (37). These variants had been found to show different geographic distributions, while some sequence variations had oncogenic potentials. In HPV 16 variants, the L83V mutation in E6 in the Swedish and Italian populations and D25E in E6 in the Japanese population were reported to be associated with the

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“…8 -10 Several North American and South American studies have shown that nonprototype-like HPV16 variants, which harbor several nucleotide changes within the long control region and the E6 gene, confer a higher risk for the development of anogenital high-grade lesions than the prototype-like variants, which contain no or only few nucleotide changes within the same regions. [11][12][13][14][15] In a follow-up study, an HPV16 E6 variant, E-G350, harboring an amino acid change at position 83 substituting a leucine for a valine (L83V), was found to be associated with progression from cervical intraepithelial neoplasia-I (CIN-I) to CIN-III. 8 We have recently shown that the same E6 variation (L83V) is more prevalent in cases of invasive cervical carcinoma (ICC) from Swedish women than the prototype.…”

Section: Abstract: Hpv16; E6 and E7 Genotypes; Polymorphism; Cervicamentioning

confidence: 99%

Human papillomavirus 16 E6 polymorphisms in cervical lesions from different European populations and their correlation with human leukocyte antigen class II haplotypes

et al. 2001

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Infection with high-risk human papillomavirus (HPV) is necessary for the development of a cervical lesion, but only a fraction of precursor lesions progress to cancer. Additional factors, other than HPV type per se, are likely to increase the probability for progression. Intratype genome variations have been reported to be associated with viral persistence and the development of a major cervical disease. We have recently shown that the prevalence of specific HPV16-E6 variants in invasive cervical cancer (ICC) varies between Italian and Swedish women. To extend our initial study we have analyzed E6 variants in cervical lesions from Czech women, ranging from low-grade cervical intraepithelial neoplasia (LCIN) to ICC and scaled up the sample size of our initial study of Swedish and Italian women. In addition, we have correlated the cases of cancers with human leukocyte antigen (HLA) class II haplotypes. In line with our earlier observation, the distribution of specific HPV16-E6 genotypes in CIN and ICC varied in the 3 cohorts. For instance, the HPV16-E6 L83V variant, which has been found to be positively associated with ICC in Swedish women (p ‫؍‬ 0.002), was more prevalent in LCIN than in ICC in Italian and Czech women (p ‫؍‬ 0.01 and ‫؍‬ 0.03, respectively). These data indicate that host genetic factors, such as HLA polymorphism, may determine the potential oncogenicity of the HPV16-E6 L83V variant. Indeed, the DR04-DQ03 haplotype, which is approximately 3-fold more abundant in the normal Swedish population than in those in Italy and the Czech Republic, was found to be positively associated with HPV16-E6 L83V in the 3 cohorts investigated (p ‫؍‬ 0.01). This observation may explain why L83V is a risk factor more in Sweden than in the other 2 countries. © 2001 Wiley-Liss, Inc. Key words: HPV16; E6 and E7 genotypes; polymorphism; cervical lesion; human leukocyte antigenCertain human papillomavirus (HPV) genotypes are etiologic agents for cervical cancer development. 1 HPV16 is the most frequently detected genotype in cervical carcinoma and its precursors. [2][3][4][5] Biochemical data have demonstrated that the products of 2 early genes, E6 and E7, are the major oncoproteins of HPV16. 6 HPV16 E6 and E7 associate with and inactivate the biologic function of several cellular proteins, including the regulators of cell cycle checkpoints, p53 and pRb. 7 Infection with high-risk HPV is the principal risk factor for the development of an invasive lesion. However, most HPV infections regress spontaneously and, for the cases that do progress to cancer, a long period of latency is normally required. It is clear that additional risk factors play a role in disease progression. Recently, independent studies have provided evidence that specific intratype HPV genome variations may influence the persistence of the infection and the progression of a precursor lesion to cancer. 8 -10 Several North American and South American studies have shown that nonprototype-like HPV16 variants, which harbor several nucleotide changes within the...

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Human Papillomavirus Type 16 Variants and Risk of Cervical Cancer

Cited by 203 publications

References 23 publications

Variants of the long control region and the E6 oncogene in European human papillomavirus type 16 isolates: implications for cervical disease

Variants of the long control region and the E6 oncogene in European human papillomavirus type 16 isolates: implications for cervical disease

Human Papillomavirus Type 16 Variant Analysis of E6, E7, and L1 Genes and Long Control Region in Identification of Cervical Carcinomas in Patients in Northeast China

Human papillomavirus 16 E6 polymorphisms in cervical lesions from different European populations and their correlation with human leukocyte antigen class II haplotypes

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