From HPV Infection to Lesion Progression: The Role of HLA Alleles and Host Immunity

Abstract

Persistent high-risk human papillomavirus (HPV) infection has been associated with increased risk for cervical precancerous lesions and cancer. The host’s genetic variability is known to play a role in the development of cervical cancer. The human leukocyte antigen (HLA) genes are highly polymorphic and have shown to be important risk determinants of HPV infection persistence and disease progression. HLA class I and II cell surface molecules regulate the host’s immune system by presenting HPV-derived peptides to T-cells. The activation of T-cell response may vary depending on the HLA allele polymorphism. The engagement of the T-cell receptor with the HPV peptide-HLA complex to create an active costimulatory signal is essential for the activation of the T-cell response. Functional peptide presentation by both HLA class I and II molecules is needed to activate efficient helper and effector T-cell responses in HPV infection recognition and clearance. Some of these HLA risk alleles could also be used as preventive tools in the detection of HPV-induced cervical lesions and cancer. These HLA alleles, together with HPV vaccines, could potentially offer possible solutions for reducing HPV-induced cervical cancer as well as other HPV-related cancers.

Evaluation of Oral Supplementation with a Casein Hydrolysate-based Formula to Favor the Clearance of HR-HPV Infections and their Derived Lesions

“…Importantly, the persistence of HR-HPV is associated with higher risk of the lesions progression to precancerous lesions and cervix cancer [44]. Therefore, being able to reduce the persistence of HR-HPV or their derived lesions with a food supplementation may help reduce the risk of cervical cancer in patients infected with HR-HPV, especially when there is no other management alternative available but to wait and see.…”

Personalized Human Papillomavirus Vaccination for Persistence of Immunity for Cervical Cancer Prevention: A Critical Review With Experts' Opinions

“…In innate immunity antigen-presenting cells (APCs), such as dendritic cells, internalize the HPV vaccine VLPs and display them on their surfaces with the help of major histocompatibility complex (MHC) genes (HLA class I and HLA class II) as endogenous or exogenous antigens, respectively (44). This triggers T cell immune responses in adaptive immunity via T cell receptors (TCR) that bind those antigens and differentiate into effector, or killer, T cells.…”

“…This triggers T cell immune responses in adaptive immunity via T cell receptors (TCR) that bind those antigens and differentiate into effector, or killer, T cells. These killer T cells mobilize the immune reaction against the VLPs peptides by the production of antibodies which act against HPV infection (44) (Figure 2).…”

Polymorphisms in endoplasmic reticulum aminopeptidase genes are associated with cervical cancer risk in a Chinese Han population

“…Persistent human papillomavirus (HPV) infection confers a high risk of cervical cancer (12,13). Since the HLA class I antigen-presenting system is responsible for the presentation of foreign and cancerous antigens to the immune system (14,15), and ERAPs downregulation was observed in cervical cancer (16,17), therefore, ERAP proteins may play crucial roles in the initiation and development of cervical cancer (18).…”