Human Papillomavirus Infections, Cervical Cancer and MicroRNAs: An Overview and Implications for Public Health

Abstract

Human Papillomavirus (HPV) is among the most common sexually transmitted infections in both females and males across the world that generally do not cause symptoms and are characterized by high rates of clearance. Persistent infections due at least to twelve well-recognized High-Risk (HR) or oncogenic genotypes, although less frequent, can occur, leading to diseases and malignancies, principally cervical cancer. Three vaccination strategies are currently available for preventing certain HR HPVs-associated diseases, infections due to HPV6 and HPV11 low-risk types, as well as for providing cross-protection against non-vaccine genotypes. Nevertheless, the limited vaccine coverage hampers reducing the burden of HPV-related diseases globally. For HR HPV types, especially HPV16 and HPV18, the E6 and E7 oncoproteins are needed for cancer development. As for other tumors, even in cervical cancer, non-coding microRNAs (miRNAs) are involved in posttranscriptional regulation, resulting in aberrant expression profiles. In this study, we provide a summary of the epidemiological background for HPV occurrence and available immunization programs. In addition, we present an overview of the most relevant evidence of miRNAs deregulation in cervical cancer, underlining that targeting these biomolecules could lead to wide translational perspectives, allowing better diagnosis, prognosis and therapeutics, and with valuable applications in the field of prevention. The literature on this topic is rapidly growing, but advanced investigations are required to achieve more consistent findings on the up-regulated and down-regulated miRNAs in cervical carcinogenesis. Because the expression of miRNAs is heterogeneously reported, it may be valuable to assess factors and risks related to individual susceptibility.

The Involvement of Natural Polyphenols in the Chemoprevention of Cervical Cancer

“…Another form of classification is related to the carcinogenic potential of the HPVs-group 1 carcinogens (carcinogenic for humans), group 2A carcinogens (probably carcinogenic for humans), and group 2B carcinogens (potentially carcinogenic for humans) [16]. Of all high-risk HPVs, the most carcinogenic are HPV16 (approximately 50% of all cervical cancers are associated with this strain) and HPV18 because they are primarily involved in squamous epithelial lesions [19]. Infection with HPV is highly associated with sexual activity, non-sexual transmission, and transmission via fomites.…”

HPV16 E6 Oncogene Contributes to Cancer Immune Evasion by Regulating PD-L1 Expression through a miR-143/HIF-1a Pathway

“…MicroRNAs are small non-coding RNA molecules of 19–25 nucleotides that target and regulate a multitude of mRNAs [ 23 ]. The observation that these molecules’ expression is differentiated in several diseases, including cancer, has put a magnifying lens on them as possible biomarkers or therapeutic targets [ 24 , 25 ]. As far as HPV-related cervical cancer is concerned, it has been reported that HPV’s oncoproteins, E6 and E7, seem to target and modify the expression of a plethora of miRNAs, consequently intervening in cellular pathways [ 23 ].…”

Screening of Precancerous Lesions in Women with Human Papillomavirus (HPV) Infection by Molecular Typing and MicroRNA Analysis

“…In general, microRNAs can regulate both the tumor suppressor and oncogenes genes and the altered expression of microRNAs represents an early event in the induction of carcinogenic by HPV infection [ 17 ]. Many studies show that in cervical cancer the expression of some microRNAs increases (miR-20a, miR-20b, miR-93, miR-224) and decreases in others (miR-127, miR-143/145, miR-218) [ 9 , 18 ]. Other studies have shown that miR-218 was higher in high-risk HPV + than in high-risk HPV negative carcinomas; furthermore, miR-146a levels were lower in p16INKa-positive (marker of high-risk HPV infection) than in p16INKa-negative samples [ 19 ].…”