Expression of apoptosis regulators in Squamous cell carcinoma of cervix and their association with Human papillomavirus 16/18 subtypes

Introduction:HPV infection is an important etiologic factor in Cervical Cancer of which the mechanismsof effect on Carcinogenesis of invasive squamous cell carcinoma of cervix is not clear yetcompletely. Limited studies have been focused on the differences between carcinogenesis ofSCCs with and without HPV infection. The main goal of this study is to determine theexpression of some of the Apoptotic pathway regulators, including P53, Bax and Bcl2 insquamous cell carcinomas with and without high risk HPV 16/18 infection.Materials and methods:42 paraffin embedded blocks with the histopathologic diagnosis of invasive SCC withdetermined HPV 16/18 status were selected; half of them were HPV positive and the restwere negative. Afterwards, IHC stained slides for p53, Bcl2 and Bax were evaluated with Hscore,multiplicative and Additive Quick score by two pathologists; in cases of controversyabout the results, the mean results were recorded.Results:Mean results and percentage of expression of our three markers were significantly higher inHPV 16/18 infected group than uninfected ones: Respectively, the mean score for Bcl2, Bax& p53 IHC staining according to H-scoring method was 68.5, 234, 106.4 in HPV 16/18infected group and 4.5, 218.8, 5.07 in uninfected group; according to Additive Quick scoringsystem was 4, 14.6, 8.2 in HPV 16/18 infected group and 1, 3, 7.9 in uninfected group andaccording to Multiplicative Quick score was 4, 14.6, 8.2 in HPV 16/18 infected group and 3,12.3, 3.5 in uninfected group.Positive reactivity percentage observed in Bcl2, Bax, p53 was 38, 100 & 85.7% of SCCs withHPV 16/18 and 4.8, 95 & 47.6% of SCCs without HPV 16/18, respectively. Bcl2, Bax & p53markers were positive in 21, 97 & 66% of all of SCCs, respectively.There was also a high correlation between H-score and Additive Quick score for each marker(correlation coefficient = 0.998, 0.657 & 0.709 for Bcl2, Bax & p53 respectively).Conclusion:High risk HPV infection (HPV 16/18) possibly act in favor of apoptotic pathway inactivation,and cause dysplasia and precancerous states, by overexpression of Bcl2 anti-apoptotic factorover the Bax apoptotic factor activity and or inactivation of p53. The significant difference inapoptotic pathway between SCCs’ with and without high risk HPVs suggests a different earlycarcinogenesis pathway.

کلیدواژه ها:

Human papilloma virus (HPV) ، Squamous cell carcinoma (SCC) of cervix ، Apoptotic factor ، Bcl2 ، Bax ، p53