Immunohistochemical Expression of Apoptosis Regulators in Squamous Cell Carcinoma of the Cervix and Their Association with Human Papillomavirus 16/18 Subtypes

Background: Human papillomavirus (HPV) infection is an important aetiological factor in squamous cell carcinoma (SCC) of the cervix. Limited studies have been focused on the differences between carcinogenesis of SCCs with and without HPV infection. Aims: The main goal of this study is to determine the expression of some of the apoptotic pathway regulators, including P53, Bax and Bcl2 in SCCs with and without high risk HPV 16/18 infection. Study Design: Cross sectional study. Methods: A total of 42 paraffin-embedded blocks with the histopathological diagnosis of invasive SCC with determined HPV 16/18 status were selected; half of them were HPV positive and the rest were negative. Afterwards, immunohistochemistry stained slides for p53, Bcl2 and Bax were evaluated with H-score, multiplicative and Additive Quick score by two pathologists; in cases of controversy about the results, the mean results were recorded. Results: Mean results and percentage of expression of our three markers were significantly higher in the HPV 16/18 infected group than in uninfected individuals: Respectively, the mean score for Bcl2, Bax and p53 staining according to H-scoring method was 68.5, 234, 106.4 in the HPV 16/18 infected group and 4.5, 218.8, 5.07 in the uninfected group; and the Multiplicative Quick score was 4, 14.6, 8.2 in the HPV 16/18 infected group and 3, 12.3, 3.5 in the uninfected group. Conclusion: High risk HPVs possibly act in favour of apoptotic pathway inactivation. The significant difference in apoptotic pathway between SCCs with and without high risk HPVs suggests a different early carcinogenesis pathway.