Cytokine response following perturbation of the cervicovaginal milieu during HPV genital infection

Abstract Human papillomaviruses (HPVs) are the most oncogenic viruses known to human, causing nearly all cervical cancers worldwide. Highly prevalent in young, sexually active women, most HPV infections are cleared within 3 years, and only a minority of those infections persist and lead to cancer later in life. To better characterize the immuno-modulatory impact of early HPV infection and more generally perturbations of the cervicovaginal milieu, we measured changes in a panel of 20 cytokines, known as highly dynamic effector molecules implicated in cell signaling. We analyzed 92 cervicovaginal samples collected from young, sexually active women who were tested for or diagnosed with HPV, chlamydia, and bacterial vaginosis. Also, symptoms associated with genital inflammation and infection were collected through self-reporting. Following a parsimonious multi-factor modeling approach, our statistical analyses revealed that increased IL-1Alpha and IL-12/IL-23p40 concentrations were associated with HPV infection. Cytokine network analysis further highlighted the role of IL-1Alpha and macrophage inflammatory proteins (MIP-3Alpha) in HPV-associated immuno-modulation.