Human papillomavirus type 16 long control region and E6 variants stratified by cervical disease stage.
OBJECTIVE
Certain intra-type variants of HPV16 have been shown to be associated with an increased risk of developing high grade cervical disease, but their potential association is confounded by apparent geographic and phylogenetic lineage dependency. The objective of this study was to evaluate the relationship between HPV16 sequence variants and cervical disease stage in monospecific infection samples from a single lineage (European, EUR) in England.


METHODS
One hundred and twelve women singly infected with HPV16 and displaying normal and abnormal cytology grades were selected. An 1187 bp fragment encompassing the entire LCR and a portion of the E6 open reading frame was sequenced to identify intra-type variants. Intra-type diversity was estimated using Shannon entropy.


RESULTS
Almost all samples (110/112; 98%) were assigned to the EUR lineage, one sample was classified as European-Asian (EAS) and another African (Afr1a). The mean pairwise distance of the EUR sequences in this study was low (0.29%; 95%CI 0.13-0.45%) but there were nevertheless several sites in the LCR (n=5) and E6 (n=2) that exhibited a high degree of entropy. None of these sites, however, including the T350G non-synonymous (L83V) substitution in E6, alone or in combination, were found to be associated with cervical disease stage.


CONCLUSIONS
Despite using single infection samples and samples from a single variant lineage, intra-type variants of HPV16 were not differentially associated with cervical disease. Monitoring intra-lineage, site-specific variants, such as T350G, is unlikely to be of diagnostic value.
Virus Reference Department, Public Health England, London, UK.
Luigi
L
Marongiu
Virus Reference Department, Public Health England, London, UK.
Anna
A
Godi
Virus Reference Department, Public Health England, London, UK.
John V
JV
Parry
Virus Reference Department, Public Health England, London, UK. Electronic address: simon.beddows@phe.gov.uk.
Simon
S
Beddows
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D052162:Human papillomavirus 16 / Q000145:classification / Q000235:genetics*; D006801:Humans; D016017:Odds Ratio; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology*; D010802:Phylogeny; D012097:Repressor Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D020079:Terminal Repeat Sequences; D002577:Uterine Cervical Diseases / Q000209:etiology* / Q000473:pathology*
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins
Cervical cancer; E6; HPV16; Human papillomavirus; LCR; Variants