Cell-cycle and suppressor proteins expression in uterine cervix in HIV/HPV co-infection: comparative study by tissue micro-array (TMA)

We analyzed the expression of Rb, p27, VEGF and Elf-1 transcriptor factor by immunohistochemistry in 163 paraffin-embeded cervical samples using Tissue Micro-Array (TMA) and correlated this to HIV-1 and HPV infection.HIV/HPV co-infection was associated with a significant increase in expression (p < 0.001) of VEGF and p27 in both low and high grade CIN when compared to the cervices of women infected by HPV alone. Decreased Rb expression was evident with increased CIN grade in the cervices of women infected with HPV alone (p = 0.003 average of cells/mm2 in CIN I: 17.9, CIN II/III: 4.8, and tumor 3.9). Rb expression increased 3-fold for both low and high grade CIN with HPV/HIV-1 co-infection compared to HPV infection alone but did not reach statistical significance. There was a significant increase in Elf-1 expression in HPV+/HIV- women with CIN II/III and tumor (average of cells/mm2 in CIN I: 63.8; CIN II/III: 115.7 and tumor: 112.0, p = 0.005), in comparison to controls.Co-infection of HPV and HIV leads to significant increase in the VEGF and p27 expression when compared to HPV+/HIV-negative infection that could facilitate viral persistence and invasive tumor development.Human papillomavirus (HPVs) are DNA viruses that produce hyperproliferative lesions in epithelial tissues. High-risk HPV genital infection, in particular HPV types 16 and 18, is associated with the development of genital cancer, while the low-risk HPVs induce benign genital warts. The oncogenic potential of HPV is, in part, mediated by the E6 and E7 proteins, which are known to bind and inactivate the p53 and retinoblastoma protein (pRb) respectively. Rb is one of the most investigated tumor suppressor genes and its dysregulation has been associated with neoplastic growth in a variety of tumors [1]. The ability of HPV oncoproteins to disrupt growth regulatory proteins may have effects on the cyclin-dependent kinase (CDK) inhibitors linked to the G1- and G2- checkpoints. A group of CDK inhibitors, whi