Pathogens and Disease, 77, 2019, ftz048 doi: 10.1093/femspd/ftz048 Advance Access Publication Date: 2 September 2019 Minireview MINIREVIEW Association of human papillomavirus infection and inflammation in cervical cancer Nima Hemmat 1,2,3 and Hossein Bannazadeh Baghi 1,2,4, * ,† 1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran, 2 Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran, 3 Drug Applied Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran and 4 Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran ∗ Corresponding author: Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, 5166/15731Tabriz, Iran. Tel/Fax: +98 41 33364661; E-mail: hbannazadeh@tbzmed.ac.ir or hb.zadeh@gmail.com One sentence summary: This review will summarize what is currently known in regard to the roles of human papillomavirus oncogenes in the occurrence of inflammation in cervical cancer and the effects of some other factors in cervical tissue. Editor: Wei Wang † Hossein Bannazadeh Baghi, http://orcid.org/0000-0002-2513-5361 ABSTRACT Human papillomavirus (HPV) associated cancers, and in particular cervical cancer, are considered to be directly stimulated by HPV oncogenes. Alternatively, these types of cancers could also be indirectly stimulated by HPV-induced chronic inflammations, which in turn are also caused by HPV oncogenes activity. Chronic inflammation is associated with repeated tissue injury and development of mutations in the vital tumor suppressor genes. Thus, it is important to understand that the persistent HPV infection and its associated chronic inflammation is responsible for the progression of HPV-induced cancers. HPV E5, E6 and E7 could upregulate the expression of cyclooxygenase (COX)-2 and prostaglandin (PG) E2 followed by the activation of the COX-PG pathway. This pathway is assumed to be the main cause of HPV-induced inflammation. Additionally, HPV oncogenes could have an impact on the upregulation of pro-inflammatory cytokines in HPV-positive patients. The upregulation of such cytokines accelerates the incidence of inflammation following HPV infection. Other factors such as microRNAs, which are involved in the inflammation pathways and aging, give rise to the increased level of pro-inflammatory cytokines and could also be responsible for the acceleration of HPV-induced inflammation and consequent cervical cancer. In this review, the exact roles of HPV oncogenes in the occurrence of inflammation in cervical tissue, and the effects of other factors in this event are evaluated. Keywords: human papillomavirus; persistent infection; inflammation; cervical cancer INTRODUCTION According to the World Health Organization (WHO) report, cer- vical cancer is the fourth most common cancer among women, with approximately 570 000 new cases in 2018 (6.6% of all female cancer) (World Health Organization 2018). Furthermore, the inci- dence and fatality of this type of cancer is striking in East African and South Asian women (Arbyn et al. 2011). Cervical cancer cases, in these regions, are usually identified when the last stage of the disease is ongoing, because of the insufficient diagnosis methods and lack of equipment (Getahun et al. 2013; Catarino et al. 2015). There are some risk factors that are considered to be culprits for the induction of this type of cancer, such as gene polymorphisms (Pillai et al. 2002; Ni et al. 2011). However, the majority of cervical cancer cases are associated with persistent human papillomavirus (HPV) infections (Schiffman et al. 2007). HPV infection could also take part through the induction of some Received: 30 May 2019; Accepted: 1 September 2019 C  FEMS 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 1 Downloaded from https://academic.oup.com/femspd/article/77/5/ftz048/5558235 by guest on 24 February 2023