Alteration of Na/H exchange regulatory factor-1 protein levels in anogenital lesions positive for mucosal high-risk human papillomavirus type 16

Abstract

Mucosal high-risk (HR) human papillomaviruses (HPV) are associated with anogenital carcinogenesis. The products of two early genes, E6 and E7, act as major viral oncoproteins. Functional studies in experimental models showed that HPV16 E6 induces degradation of the PDZ protein, the Na+/H+ exchanger regulatory factor-1 (NHERF-1). Here, we determined NHERF-1 protein levels by immunohistochemistry (IHC) in (i) benign anogenital warts (n = 8) (ii) premalignant lesions (L-SIL and H-SIL) (n = 43) and (iii) invasive cervical squamous cell carcinomas (SCC) (n = 17). A decrease of NHERF-1 protein level was not observed in genital warts in comparison to healthy epithelium. Conversely, a clearly decrease in NHERF-1 protein levels was observed in HPV16-positive pre-malignant and malignant lesions, while the phenomenon was much attenuated in lesions induced by other HR HPV types. In conclusion, these findings show that mucosal HPV types differently impact on NHERF-1 protein level in benign and malignant anogenital lesions.