Article

Risks for persistence and progression by human papillomavirus type 16 variant lineages among a population-based sample of Danish women.

International Agency for Research on Cancer, Lyon, France.
Cancer Epidemiology Biomarkers &amp Prevention (impact factor: 4.12). 06/2011; 20(7):1315-21. DOI:10.1158/1055-9965.EPI-10-1187 pp.1315-21
Source: PubMed

ABSTRACT Little is known about factors determining HPV16 persistence and progression, but several studies have suggested that genetic variants may play a role.
HPV16-positive women with normal cytology in a large Danish cohort were reassessed for HPV16 status at 2 years and followed-up for cervical intraepithelial neoplasia 3 or worse (CIN3+) over 11 years through linkage with a national pathology database. Relative risks for clearance, persistence, and progression were compared with different HPV16 variant lineages based upon E6 gene sequencing.
Sixty-two (23.7%) of 261 HPV16 infections were persistent at 2 years, and 32 (51.6%) persistent infections progressed to CIN3+. The majority of baseline infections belonged to the European lineage (97.3%), with EUR-350T and EUR-350G accounting for 61.3% and 36.0% of infections, respectively. At two years, the proportion of HPV16 infections that persisted was significantly higher for EUR-350T (28.2%) than EUR-350G (15.9%) variants (odds ratio = 2.06, 95% CI, 1.04-4.25). This increased risk for persistence was consistent both in the absence (OR = 2.16, 95% CI, 0.84-6.26) or presence (OR = 1.89, 95% CI, 0.76-5.15) of progression to CIN3+. Among persistent HPV16 infections, there was no significant difference in risk of progression to CIN3+ between EUR-350T and EUR-350G sub-lineages, which were both associated with a substantial absolute risk (>50%) of CIN3+.
Significant differences in risk for persistence exist between the HPV16 variants that predominate in Europe.
Understanding the genetic basis of HPV16 persistence and carcinogenicity may help unravel important interactions between HPV16 and the host immune system.

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    Article: Sequence imputation of HPV16 genomes for genetic association studies.
    Benjamin Smith, Zigui Chen, Laura Reimers, Koenraad van Doorslaer, Mark Schiffman, Rob Desalle, Rolando Herrero, Kai Yu, Sholom Wacholder, Tao Wang, Robert D Burk
    [show abstract] [hide abstract]
    ABSTRACT: Human Papillomavirus type 16 (HPV16) causes over half of all cervical cancer and some HPV16 variants are more oncogenic than others. The genetic basis for the extraordinary oncogenic properties of HPV16 compared to other HPVs is unknown. In addition, we neither know which nucleotides vary across and within HPV types and lineages, nor which of the single nucleotide polymorphisms (SNPs) determine oncogenicity. A reference set of 62 HPV16 complete genome sequences was established and used to examine patterns of evolutionary relatedness amongst variants using a pairwise identity heatmap and HPV16 phylogeny. A BLAST-based algorithm was developed to impute complete genome data from partial sequence information using the reference database. To interrogate the oncogenic risk of determined and imputed HPV16 SNPs, odds-ratios for each SNP were calculated in a case-control viral genome-wide association study (VWAS) using biopsy confirmed high-grade cervix neoplasia and self-limited HPV16 infections from Guanacaste, Costa Rica. HPV16 variants display evolutionarily stable lineages that contain conserved diagnostic SNPs. The imputation algorithm indicated that an average of 97.5±1.03% of SNPs could be accurately imputed. The VWAS revealed specific HPV16 viral SNPs associated with variant lineages and elevated odds ratios; however, individual causal SNPs could not be distinguished with certainty due to the nature of HPV evolution. Conserved and lineage-specific SNPs can be imputed with a high degree of accuracy from limited viral polymorphic data due to the lack of recombination and the stochastic mechanism of variation accumulation in the HPV genome. However, to determine the role of novel variants or non-lineage-specific SNPs by VWAS will require direct sequence analysis. The investigation of patterns of genetic variation and the identification of diagnostic SNPs for lineages of HPV16 variants provides a valuable resource for future studies of HPV16 pathogenicity.
    PLoS ONE 01/2011; 6(6):e21375. · 4.09 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

2 years
 
baseline infections
 
cervical intraepithelial neoplasia 3
 
different HPV16 variant lineages
 
EUR-350G accounting
 
EUR-350G sub-lineages
 
genetic basis
 
genetic variants
 
host immune system
 
HPV16 infections
 
HPV16 persistence
 
HPV16 status
 
HPV16 variants
 
HPV16-positive women
 
increased risk
 
large Danish cohort
 
national pathology database
 
persistent HPV16 infections
 
Relative risks
 
substantial absolute risk