Cigarette Smoking Promotes Infection of Cervical Cells by High-Risk Human Papillomaviruses, but not Subsequent E7 Oncoprotein Expression.

Kimon Chatzistamatiou,Erwin Soutschek,Oliver Boecher,Pidder Jansen-Duerr,Theodoros Moysiadis,Ekaterini Chatzaki,Andreas Kaufmann,Theodoros Agorastos,Athena Tsertanidou,Dimos Vryzas,Isabel Koch,Nikolaos Maglaveras

doi:10.3390/ijms19020422

Abstract

Persistent cervical infection with high-risk human papillomaviruses (hrHPVs) is a necessary, but not sufficient, condition for the development of cervical cancer. Therefore, there are other co-factors facilitating the hrHPV carcinogenic process, one of which is smoking. To assess the effect of smoking on high-risk (hr) HPV DNA positivity and on the expression of HPV E7 oncoprotein, as a surrogate of persistent hrHPV infection, we used data from women recruited for the PIPAVIR project, which examined the role of E7 protein detection in cervical cancer screening. Women were tested for hrHPV DNA, using Multiplex Genotyping (MPG), and E7 protein, using a novel sandwich ELISA method, and gave information on their smoking habits. Among 1473 women, hrHPV prevalence was 19.1%. The odds ratio (OR) for hrHPV positivity of smokers compared to non-smokers was 1.785 (95% confidence intervals (CI): 1.365–2.332, p < 0.001). The ORs for E7 positivity, concerning hrHPV positive women, ranged from 0.720 to 1.360 depending on the E7 detection assay used, but this was not statistically significant. Smoking increases the probability of hrHPV infection, and smoking intensity is positively associated to this increase. Smoking is not related to an increased probability of E7 protein positivity for hrHPV positive women.

Highlights

Persistent cervical infection with high-risk human papillomaviruses is a necessary condition for the development of cervical cancer since it has been shown that virtually all cases of cervical cancer are related to HPV DNA detection [1]
The current analysis was conducted on 1473 women aged 30–60 years old who were enrolled for the PIPAVIR project and for whom there was a valid result for high-risk human papillomaviruses (hrHPVs) DNA genotyping and E7 protein detection
High-risk HPV prevalence for the study population was 19.1% (282 women found positive for hrHPV out of 1473) (Table 1)

Summary

Introduction

Persistent cervical infection with high-risk human papillomaviruses (hrHPVs) is a necessary condition for the development of cervical cancer since it has been shown that virtually all cases of cervical cancer are related to HPV DNA detection [1]. The most important factors identified as co-factors to cervical carcinogenesis in hrHPV positive women are high parity, long-term oral contraceptive (OC) use, smoking, and co-infection with other sexually transmitted agents [3]. Smoking has been shown to be a factor associated to a higher probability of hrHPV infection by studies based on hrHPV DNA detection [5,6,7]. Persistent hrHPV infection, characterized by the expression of E6 and E7 oncoproteins, which play a crucial role in HPV-related carcinogenesis [8], has not yet been studied thoroughly concerning probable associations to smoking

Methods

Results

Conclusion