Abstract # 83:

Scheduled for Friday, June 22, 2007 09:50 AM-10:05 AM: Session 8 (North Main Hall C/D) Symposium

A Macaque Model for Cervical Cancer

C. E. Wood1, Z. Chen2, J. M. Cline1, B. E. Miller1 and R. D. Burk2
1Wake Forest University School of Medicine, Winston-Salem, NC, USA, 2Albert Einstein College of Medicine, Bronx, NY, USA
     Most all cases of cervical cancer in women are caused by specific types of genital human papillomavirus (HPV). In this study we used PCR-based methods to evaluate naturally-occurring genital papillomaviruses in exfoliated cervical cells obtained from socially-housed female cynomolgus macaques (Macaca fascicularis) with no breeding contact for at least 3 years. Nineteen of 54 animals (35%) tested positive for at least 1 of 7 unique papillomavirus. Four of the macaque papillomaviruses were associated with cervical intraepithelial neoplasia (CIN) which closely resembled HPV-induced lesions on histology, cytology, colposcopy, and immunohistochemistry. The presence of cervical neoplasia was highly associated with papillomavirus infection [2-sided Fisher's Exact Test, a=0.05]. The most common virus type was RhPV-d, which accounted for 47% of typed infections. An RhPV-d genome was sequenced from a high-grade CIN lesion and found to be phylogenetically related to the uniquely oncogenic HPV16. Transfer of cervical cells from donor animals naturally infected with RhPV-d resulted in new viral infections in 4 of 12 (33%) virus-free animals and abnormal cytology and histology in 1 of 4 infected animals after 24 weeks. Active experimental infections were confirmed by identification of spliced E1^E4 mRNA transcripts in exfoliated cell samples and RhPV-d sequence identity with the donor variant. These findings identify similarities between macaque and high-risk human genital papillomaviruses and suggest that the macaque may be a useful model for the study of cervical oncogenesis.