Human Papillomavirus (HPV) and how HPV infection causes cervical cancer

Human Papillomavirus also known as HPV is an extremely common sexually transmitted infection. Essentially every person who is sexually active will contract HPV at some point in their life. There are over a hundred different types of HPV and in particular can cause warts or certain types of cancer. HPV infections usually clear up without any intervention within a few months after acquisition, and about 90% clear within 2 years. A small proportion of infections with certain types of HPV can persist and progress to cervical cancer. It is the major risk factor for the development of high-grade precancerous and cervical carcinoma.

     [ Human Papillomavirus ]

Types of HPV: HPVs can infect basal epithelial cells of the skin or inner lining of tissues and are categorized as cutaneous types or mucosal types. Cutaneous types of HPV are epidermitrophic and target the skin of the hands and feet. Mucosal types infect the lining of the mouth, throat, respiratory tract, or anogenital epithelium. Mucosal HPV types can be further sub-divided into low risk (LR-HPV) mainly associated with benign warts and high risk (HR-HPV) defined by their risk of progression to malignancy. About 70% of all cases are mainly caused by HPV-16 and HPV-18.

Classification of HPVs

GroupHPV Types
Established high-risk (Carcinogens)16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59
Probably high-risk (Possibly carcinogenic)26, 53, 66, 68, 73, 82
Established low-risk (Non-Carcinogenic)6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, CP6108

HPV Genome: Papillomavirus are part of the Papollomaviridae family. They are small, non-enveloped viruses with icosahedral capsids and double stranded DNA genomes. Human Papillomavirus particles consist of ~8000 base-pair long circular DNA molecules wrapped into a protein shell that is composed of two molecules (L1 and L2). The genome has the coding capacity for these two proteins and at least six so-called early proteins (E1, E2, E4, E5, E6 and E7) that are necessary for the replication of the viral DNA and for the assembly of newly produced virus particles within the infected cells.

Molecular Mechanism of HPV Infection – Role of E6 and E7: The critical molecules in viral replication are E6 and E7, which functionally inactivate the products of two important tumor suppressor genes, p53 and pRb, respectively. Both oncoproteins induce proliferation, immortalization and malignant transformation of the infected cells. E6 acts as repressor of apoptosis and mediates survival of severely damaged cells, while E7 functions as promoter for replication and cell growth by inactivation of major tumor suppressors, p53 and pRB, respectively.  Both can independently immortalize human cells, but their joint function gives rise to an interesting complementary and synergistic effect, inducing a marked increase in transforming activity.

HPV Transmission and Carcinogenesis: Cervical stratified squamous epithelial cell architecture and the expression of HPV proteins after infection. Daughter cells of epithelial stem cells divide along the basement membrane and then mature vertically through the epithelium without further division. After the introduction of HPV into the stem cells in the basal layer of the epithelium, expression of viral non-structural proteins occurs. Under the regulation of these proteins, the dividing cell population expands vertically and epithelial cell differentiation is delayed and is less complete. Viral proteins are expressed sequentially with differentiation and mature virions are produced only in the most superficial layers of the epithelium. Intraepithelial antigen-presenting cells (APCs) are depleted in the HPV-infected epithelium.

  Written By: Rubina Polara

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