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 eventin cervical carcinogenesis. This study concerned whether HPV16 status and E2 gene intactness are predictive ofradiation response in patients with cervical cancer. Materials and
Methods: Biopsies of 44 patients with cervicalcancer were collected before or after radiotherapy. The presence of HPV16 was assessed by polymerase chainreaction (PCR) using specific primers for the L1 region. E2 disruption was detected by amplifying the entire E2gene.
Results: HPV16 DNA was found in 54.5% of the clinical samples. Overall, 62.5% of the HPV16 positivetumors had integrated viral genome and 37.5% had episomal genome. There was a tendency of increase ofHPV16 E2 negative tumors compared with HPV16 L1 ones in advanced stages (75% versus 20% in stage IIIrespectively). Detection of E2 gene appeared influenced by the radiotherapy treatment, as the percentage ofsamples containing an intact HPV16 E2 was more frequent in pretreated patients compared to radiotherapytreated 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 doseof 50Gy.
Conclusions: This study reveals that the status of the viral DNA may be used as a marker to optimizethe radiation treatment.