Variation in the E2-binding domain of HPV 16 is associated with high-grade squamous intraepithelial lesions of the cervix.
Human papillomaviruses (HPV) are strongly associated with cervical intraepithelial neoplasia (CIN) and invasive cancer mainly through the action of the E6 and E7 viral proteins, transcription of which is down-regulated by the E2 protein. To test the hypothesis that HPV 16 E2 variation is important in the development of high-grade squamous neoplasia of the cervix, we carried out a cross-sectional analysis of low-grade and high-grade squamous intraepithelial lesions (SILs) for specific mutations in the HPV 16 E2 gene and for E2 gene disruption in these regions. Isolates were also analysed for the HPV 16 350T-G variant. 22 of 178 low-grade SILs and 43 of 61 high-grade SILs examined, contained HPV 16. No relationship was found between the E6 350T-G variant, or the E2 hinge region 3410C-T variant, and lesion grade. However, disruption of the regions of E2 analysed was significantly more frequent in high-grade lesions, and there was a significant association between the 3684C-A variant in the E2 DNA binding domain and high-grade histology suggesting that this variant may be important in progression to high-grade intraepithelial disease.
Giannoudis
A
A
Department of Pathology, University of Liverpool, Royal Liverpool University Hospital, Duncan Building, Daulby Street, Liverpool, L69 3GA, UK.
Duin
M
M
Snijders
P J
PJ
Herrington
C S
CS
D001665:Binding Sites / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D014644:Genetic Variation; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D014412:Tumor Virus Infections / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000821:virology*
D004279:DNA, Viral; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral