Human Papillomavirus (Hpv) Typing in Relation to ras Oncogene mRNA Expression in HPV-Associated Human Squamous Cervical Neoplasia

Abstract

Human papillomavirus (HPV) has been identified as the principal etiologic agent for cervical cancer and its precursors. Different HPV types have been associated with different oncogenic potential. The purpose of this study was to evaluate the relationship between specific HPV type infection and expression pattern of the ras family oncogenes in different grades of HPV-associated human cervical neoplasia. HPV typing was performed using polymerase chain reaction (PCR) in 31 HPV-positive human cervical specimens from patients with squamous intraepithelial lesions (SIL) or squamous cervical carcinoma (SCC). The mRNA expression levels of H-, K- and N-ras oncogenes were examined using the reverse transcriptase polymerase chain reaction (RT-PCR) technique. Statistical analyses were performed using SPSS software. Among patients with SCC, H-, K- and N-ras expression levels were higher in HPV 16/18-associated cases compared to HPV 16/18-unassociated samples (p=0.003, p=0.004 and p=0.0001, respectively). The expression levels for H-, K- and N-ras were significantly higher in SCC patients with multiple HPV infection compared with SCC patients with single HPV infection (p=0.009, p=0.01 and p=0.021, respectively). Among patients with SIL, no statistically significant relationship was found between ras expression and HPV status. Our findings indicate the possible role of ras signaling interaction with "high-risk" HPV 16/18 and multiple HPV infection in cervical cancer development.