Situation of HPV16 E2 gene status during radiotherapy treatment of cervical carcinoma.
BACKGROUND
Human papillomavirus (HPV) integration within the E2 gene has been proposed as a critical event in cervical carcinogenesis. This study concerned whether HPV16 status and E2 gene intactness are predictive of radiation response in patients with cervical cancer.


METHODS
Biopsies of 44 patients with cervical cancer were collected before or after radiotherapy. The presence of HPV16 was assessed by polymerase chain reaction (PCR) using specific primers for the L1 region. E2 disruption was detected by amplifying the entire E2 gene.


RESULTS
HPV16 DNA was found in 54.5% of the clinical samples. Overall, 62.5% of the HPV16 positive tumors had integrated viral genome and 37.5% had episomal genome. There was a tendency of increase of HPV16 E2 negative tumors compared with HPV16 L1 ones in advanced stages (75% versus 20% in stage III respectively). Detection of E2 gene appeared influenced by the radiotherapy treatment, as the percentage of samples containing an intact HPV16 E2 was more frequent in pretreated patients compared to radiotherapy treated patients (66.6% versus 20%). The radiation therapy caused an eight-fold [OR= 8; CI=1.22-52.25; p=0.03] increase in the risk of HPV16 genome disruption. The integration status is influenced by the irradiation modalities, interestingly E2 disruption being found widely after radiotherapy treatment (75%) with a total fractioned dose of 50 Gy.


CONCLUSIONS
This study reveals that the status of the viral DNA may be used as a marker to optimize the radiation treatment.
Unit of Immunology Microbiology Environmental and Carcinogenesis (IMEC), Science Faculty of Bizerte, University of Carthage, Jarzouna, Bizerte, Tunisia E-mail : oueslatiridha12@hotmail.fr.
Saloua
S
Kahla
Lotf
L
Kochbati
Mongi
M
Maalej
Ridha
R
Oueslati
D000230:Adenocarcinoma / Q000235:genetics* / Q000532:radiotherapy / Q000821:virology; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000532:radiotherapy / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D016679:Genome, Viral; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D030361:Papillomavirus Infections / Q000235:genetics* / Q000532:radiotherapy / Q000821:virology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000532:radiotherapy / Q000821:virology; D016662:Virus Integration
D004279:DNA, Viral; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral