Sequence variation and physical state of human papillomavirus type 16 cervical cancer isolates from Australia and New Caledonia

Watts, Kylie J.; Thompson, Carol H.; Cossart, Yvonne E.; Rose, Barbara

doi:10.1002/ijc.10103

Cited by 33 publications

(23 citation statements)

References 29 publications

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“…However, the prevalence of episomal HPV diverged between the different HPV types. For HPV types 16 and 18, additional episomal HPV was found in 55% and 4% of the samples, respectively, which is in accordance with previous findings (7,18,21,48). For HPV types 31 and 33, data on HPV integration are limited.…”

Section: Discussionsupporting

confidence: 90%

Presence of E6 and E7 mRNA from Human Papillomavirus Types 16, 18, 31, 33, and 45 in the Majority of Cervical Carcinomas

et al. 2006

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The oncogenic potential of the human papillomavirus (HPV) early genes E6 and E7 is well established and a source of interest with regard to HPV testing for cervical carcinoma. Here we present a study performed with 204 histologically confirmed invasive cervical squamous cell carcinomas (SCCs) in which we evaluated the HPV E6 and E7 mRNA detection assay PreTect HPV-Proofer for detection of high-risk HPV types 16, 18, 31, 33, and 45. For further evaluation, detection of E6 and E7 mRNA from HPV types 35, 52, and 58 by real-time multiplex nucleic acid sequence-based amplification was also included. For comparison and to assess the overall prevalence of various HPV types, samples were also tested for HPV DNA by both consensus and type-specific PCR, reverse line blotting, sequencing, and in situ hybridization. The overall prevalence of HPV was 97%. HPV E6 and E7 transcripts were detected in 188 of 204 (92%) biopsy specimens, of which 181 contained one of the following HPV types: 16, 18, 31, 33, or 45. Consensus PCR and type-specific PCR detected HPV in 187 of 204 and 188 of 204 (92%) specimens, respectively. In conclusion, this study verifies the presence of HPV E6 and E7 mRNA in SCCs and demonstrates that HPV infections among Norwegian women with SCCs are limited mainly to the five high-risk types, 16, 18, 31, 33, and 45. This, together with the fact that PreTect HPV-Proofer detects the HPV oncogenic transcripts, suggests that the assay is a valuable approach in the field of HPV detection in cervical carcinoma.The presence of human papillomavirus (HPV) infection in the majority of cases of cervical neoplasia has been considered evidence of an etiological role of HPV in cervical cancer. The association is strong, consistent, and specific to a limited number of viral types (2,5,32,46). On the other hand, the lifelong risk of HPV infection is 80%, and only a small proportion of women infected with HPV will develop high-grade cervical neoplasia (42). Among HPV-positive women, it is therefore of the utmost importance to identify those with an increased risk of developing cervical carcinoma by either methods that reveal persistent HPV infection (38), methods that detect viral oncogene expression (40), or the use of additional human markers for cervical carcinogenesis (45).The most frequent HPV types found in cervical intraepithelial neoplasia and squamous cell carcinoma (SCC) are HPV type 16 (HPV-16) and HPV-18, which in 1995 were classified as human carcinogens by the International Agency for Research on Cancer. In total, based on their high frequencies in carcinomas, 13 HPV types are now considered carcinogenic types (6). In the largest multinational studies performed so far, HPV types 16, 18, 31, 33, and 45 were shown to be the most prevalent types associated with cervical carcinomas (2, 22, 32), with HPV-16 alone found in more than 50% of the cases. The oncogenic potential of these high-risk HPV types lies in the oncoproteins E6 and E7, which bind to and modulate a number of different gene products, in particular, the ...

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Section: Discussionsupporting

confidence: 90%

Presence of E6 and E7 mRNA from Human Papillomavirus Types 16, 18, 31, 33, and 45 in the Majority of Cervical Carcinomas

et al. 2006

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“…A substantial proportion of the changes found in HPV16 E6 were located in the amino half of the protein, which represents the binding region of the cellular protein E6-AP and has a role in both cell-mediated and humoral host immune responses (26,40,41). Moreover, a recent report indicates that variations in codons 14 and 27 substantially altered the E6 antigenic index and may affect interactions with E6-AP (66). This provides biochemical support for selection at HPV16 E6 aa 14.…”

Section: Discussionmentioning

confidence: 76%

Diversifying Selection in Human Papillomavirus Type 16 Lineages Based on Complete Genome Analyses

Chen¹,

Terai²,

Fu³

et al. 2005

J Virol

155

142

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Papillomaviruses are a heterogeneous group of DNA viruses with closed circular double-stranded DNA genomes of about 8 kb in size that contain three general regions. An upstream regulatory region (URR) contains sequences that control transcription and replication, an early region contains genes (e.g., E6, E7, E1, E2, E4, and E5) involved primarily in enzymatic activities, and a structural region produces the L1 capsid protein and L2, which facilitates packaging of the viral DNA. Human papillomaviruses (HPVs) are classified by the sequence similarity of their genomes. A cloned HPV genome whose L1 open reading frame (ORF) displays less than 90% similarity to previously designated types is defined as a novel type. To date, more than 90 different genotypes of the HPV have been fully characterized (21). Intratypic variants and subtypes are defined as HPVs that vary by less than 10% in their L1 DNA sequences (5, 21).HPVs are causally involved in the etiology of cervical cancer and its precursor lesions (16,17,43,49). Of the high-risk HPV types associated with cervical cancer, HPV16 is the most prevalent and is found in approximately half of all cancers (7, 49). Numerous variants of HPV16 have been identified in different geographic locations and ethnic groups (35,42,53,68). Although all HPV16 isolates are closely related, previous studies inferred five distinct phylogenetic branches among HPV16 variants: European (E), Asian (As), Asian-American (As-Am), African-1 (Af-1), and African-2 (Af-2), corresponding to the geographic locations from which the samples were obtained (12,34). Subsequent studies by sequence analyses of the HPV16 variants in other genomic regions (e.g., E6, L2, and L1) expanded and complemented this phylogenetic hypothesis (69).Although HPV16 variants are an important focus of phylogenetic studies and the molecular variants of E2, L2, L1, the URR, and especially the E6 region have been described in detail previously (28), covariation among different ORFs belonging to the same lineage or isolate have not been studied in great detail. HPV16 variants have demonstrable differences in biological properties in vitro which may be responsible, in part, for differences in pathogenicity, carcinogenic risk, and perhaps immunogenicity (28). Furthermore, HPV16 variants are associated with different cervical cancer risks (6,32,65,67). Although the diversifying selection in the HPV16 E6 and E7 oncogenes has been described recently (20), the evolutionary basis of the entire genome, coevolutionary mechanisms among different HPV16 genes, and their underlying biological significance remain unknown. Obtaining whole-genome sequences representative of the major HPV16 variants allowed us to determine with certainty nucleotide and amino acid sequence changes that are of potential evolutionary importance.Comparison of synonymous (silent; d S ) and nonsynonymous

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“…When designing primers, the National Center for Biotechnology Information (NCBI) database was interrogated to target regions of homology across all registered HPV16 and HPV18 variants. We also reviewed reports identifying polymorphisms in the HPV16 and HPV18 E2 genes with a view to ensuring that disruption of E2 could not be explained by the failure of primer binding due to sequence variation (15)(16)(17)(18)(19)(20)(21)(22)(23).…”

Section: Methodsmentioning

confidence: 99%

Disruption of the E2 Gene Is a Common and Early Event in the Natural History of Cervical Human Papillomavirus Infection: A Longitudinal Cohort Study

Collins

Constandinou-Williams

Kong

et al. 2009

Cancer Research

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Integration of high-risk human papillomavirus (HPV) types into the host-cell genome disrupts the HPV regulatory E2 protein, resulting in a loss of negative feedback control of viral oncogene expression; this disruption has been considered a critical event in the pathogenesis of cervical neoplasia, and a potential biomarker of progressive disease. However, using serial samples taken from a cohort of young women who were recruited soon after they first had sexual intercourse, we show that disruption of the E2 gene is a common and early event in the natural history of incident cervical HPV infections. The E2 gene was significantly more likely to be disrupted in women who tested positive for HPV18 in their baseline sample than in those who tested positive for HPV16 [26% versus 58%; relative risk, 2.26; 95% confidence interval (CI), 1.38-3.71; C 2 , 9.23; 1 degree of freedom (df); P = 0.002]. Among women with an intact E2 gene in their baseline sample, the median time to first detection of E2 disruption was also shorter for those who tested positive for HPV18 than HPV16 (5.7 versus 10.9 months; hazards ratio, 1.93; 95% CI, 0.84-4.44; C 2 , 2.49; 1 df; P = 0.11).This tendency for HPV18 to integrate early, coupled with the substantial reduction in viral load in HPV18-positive samples in which E2 is disrupted, may explain why HPV18-associated disease is often reported to be characterized by minor cytologic changes, which underestimate the severity of the underlying histologic abnormality. [Cancer Res 2009; 69(9):3828-32]

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Sequence variation and physical state of human papillomavirus type 16 cervical cancer isolates from Australia and New Caledonia

Cited by 33 publications

References 29 publications

Presence of E6 and E7 mRNA from Human Papillomavirus Types 16, 18, 31, 33, and 45 in the Majority of Cervical Carcinomas

Presence of E6 and E7 mRNA from Human Papillomavirus Types 16, 18, 31, 33, and 45 in the Majority of Cervical Carcinomas

Diversifying Selection in Human Papillomavirus Type 16 Lineages Based on Complete Genome Analyses

Disruption of the E2 Gene Is a Common and Early Event in the Natural History of Cervical Human Papillomavirus Infection: A Longitudinal Cohort Study

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