Physical status of the E2 human papilloma virus 16 viral gene in cervical preneoplastic and neoplastic lesions.
BACKGROUND
Integration of human papilloma virus (HPV) 16 DNA is considered an important genetic change in cervical lesion progression towards ICC. The viral E2 gene is often disrupted by this process, releasing suppression of viral E6/E7 oncogenes, a key factor for oncogenic progression.


OBJECTIVE
To evaluate the physical status of HPV 16 E2 gene in cervical preneoplastic and neoplastic lesions and its relation with lesion severity.


METHODS
A sensitive PCR approach for the detection of an intact E2 HPV 16 gene in infected epithelial cells from the cervix with low grade squamous intraepithelial lesion (LGSIL), high grade squamous intraepithelial lesion (HGSIL) and invasive cervical carcinoma (ICC) diagnosis was applied. The correlation between gene disruption and lesion stage was examined.


RESULTS
Sixty-two LGSIL, 39 HGSIL and 24 ICC samples were analyzed. Fifty-seven LGSIL [92%], 13 HGSIL [33%] and 4 ICC [17%] showed results compatible with an intact E2 gene, while 5 LGSIL [8%], 26 HGSIL [67%] and 20 ICC [83%] samples gave no signal.


CONCLUSIONS
HPV 16 E2 gene disruption showed a positive correlation with cervical lesion progression, particularly from LGSIL to HGSIL. Although additional genetic events are very likely to be needed for HGSIL to ICC progression, the E2 gene disruption is a putative early marker to consider in the prognostic analysis of HPV 16 chronically infected women.
Tonon
S A
SA
Laboratorio de Biologia Molecular Aplicada, Facultad de Ciencias Exactas, Quimicas y Naturales, Universidad Nacional de Misiones, Felix de Azara 1552, Posadas, Misiones 3300, Argentina. tonon@arnet.com.ar
Picconi
M A
MA
Bos
P D
PD
Zinovich
J B
JB
Galuppo
J
J
Alonio
L V
LV
Teyssie
A R
AR
D000328:Adult; D000368:Aged; D002584:Cervix Uteri / Q000473:pathology / Q000821:virology; D004268:DNA-Binding Proteins; D018450:Disease Progression; D004848:Epithelium / Q000821:virology; D005260:Female; D005814:Genes, Viral; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology*; D016133:Polymerase Chain Reaction; D014412:Tumor Virus Infections / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*
D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral