Summary
Human papillomaviruses (HPV) are a group of extremely common and genetically heterogeneous DNA-containing viruses that affect the epithelium of the skin and mucous membranes. Human papillomavirus belongs to the papillomavirus family, and more than 450 HPV types have been identified and described (Barley et al., 2020). Depending on the oncogenic potential, viruses of high and low oncogenic risk are isolated. HPV virions are spherical, up to 55 nm in diameter, encapsulated by a capsid with a cubic symmetry type, which is built from 72 capsomeres (Barley at al., 2020). The genome is represented by a cyclically closed double-stranded DNA with a molecular weight of 3-5 mD, and the isolated DNA of the virus has infectious and transforming properties (Barley et al., 2020). The virion contains two layers of structural proteins, denoted by the letter E (Barley et al., 2020). Internal proteins connected to DNA are cellular histones, and capsid proteins are type-specific antigens.
HPV Infectious Cycle
HPV reproduction occurs in the nuclei of cells, where viral DNA is present in the form of an episome. This is the first feature that distinguishes HPV from other oncogenic DNA-containing viruses, which can embed the genome into the DNA of the transformed cell (Manini & Montomoli, 2018). The second distinguishing feature of HPV is that the state of the host cell regulates the expression of the viral genome (Manini & Montomoli, 2018). However, the viral gene responsible for replicating cellular DNA can also be transcribed, causing the host cell to divide again and again along with HPV, resulting in a productive type of inflammation (Barley et al., 2020). HPV infects epithelial cells, causing the appearance of skin warts and papillomas of the mucous membrane of the genitourinary, respiratory, and digestive tracts. It is also important to note that papillomaviruses are adapted to a specific type of host. Several hundred species of papillomaviruses infect mammals, birds, and reptiles, causing them to form benign tumors – papillomas, also called warts.
According to existing concepts, HPV infects the cells of the basal layer of the epithelium, penetrating through microscopic damage to the skin and mucous membranes. Viral particles first attach to cell membrane proteins with the participation of the L1 protein, then enter the cytoplasm by receptor endocytosis mediated by the cellular protein integrin (Barley et al., 2020). Viral DNA is released from the capsid with the participation of the L2 protein and enters the cell nucleus (Barley et al., 2020). During a productive infection in an affected cell that does not lose its ability to divide, viral DNA replication occurs synchronously with cell DNA replication with the participation of viral proteins E1 and E2 (Barley et al., 2020). This ensures the maintenance of a small number of copies of the viral genome in the form of episomes in the cytoplasm of the cells of the basal layer of the epithelium for some time.
Characteristics of HPV Infection
The main clinical features of HPV infection are a latent course and a weak immune response. Moreover, clinical signs of HPV infection vary depending on the type of virus and localization of formations. Morphologically, the formations are papillomas with a wide or thin base, that reside on the eyelids, neck, shoulders, and other skin expanses in the form of filamentous outgrowths (Sabatini & Chiocca, 2020). In common and plantar warts, thickening and excessive keratinization of the surface layers of cells are expressed. Pointed papillomas of the anogenital region are usually soft, lobulated, and abundantly vascularized, with lymphocytic infiltration in the stalk (Wang et al., 2020). It is known that with chronic mechanical irritation, warts can reach 3-5 cm in diameter.
Cell proliferation and differentiation, accompanied by replication of the viral genome, transcription and translation of viral proteins, and assembly of virions, are morphologically manifested as koilocytosis and the appearance of visually observed papillomas and condylomas. It is these areas of the skin that are dangerous in relation to contact infection. Infectious viral particles enter the environment as the cells of the surface layers of the epithelium are shed (Manini & Montomoli, 2018). This is typical for papillomas and for mild damage of the cervical epithelium caused by HPV of low and high carcinogenic risk.
HPV Impact
The two highly oncogenic HPV types (16 and 18) account for the majority of various cancer incidents. Among them are the cases of cervical cancer, vulvar and vaginal cancer, anal cancer, oral cavity cancer, oropharyngeal cancer, and penile cancer (Kombe Kombe et al., 2021). At the same time, the 16th type has the highest carcinogenic potential. HPV genotypes 6 and 11 cause almost all types of anogenital warts and most cases of recurrent respiratory papillomatosis, which occurs mainly in children under 5 years of age or in persons 20-30 years of age (Kombe Kombe et al., 2021). Unfortunately, there is no cure for the virus itself – therapy is reduced to the elimination of symptoms and the fight against the possible consequences of HPV: precancerous and cancerous conditions. Warts and papillomas are usually physically removed by various methods. HPV prevention includes vaccination as a major intervention against the infection, among other factors such as healthy lifestyle and sexual cautiousness. However, vaccination is most effective only if the body has never encountered a virus. Therefore, it is recommended that children be vaccinated between the ages of 9 and 14, prior to the onset of sexual activity (Wang et al., 2020). Additional revaccination can be performed later in life to help further prevent the infection.
References
Burley, M., Roberts, S., & Parish, J. L. (2020). Epigenetic regulation of human papillomavirus transcription in the productive virus life cycle. Seminars in Immunopathology, 42(2), 159–171. Web.
Kombe Kombe, A. J., Li, B., Zahid, A., Mengist, H. M., Bounda, G.-A., Zhou, Y., & Jin, T. (2021). Epidemiology and burden of human papillomavirus and related diseases, molecular pathogenesis, and vaccine evaluation. Frontiers in Public Health, 8. Web.
Manini, I., & Montomoli, E. (2018). Epidemiology and prevention of Human Papillomavirus. Annali Di Igiene: Medicina Preventiva e Di Comunita, 30(4 Supple 1), 28–32. Web.
Sabatini, M. E., & Chiocca, S. (2019). Human papillomavirus as a driver of head and neck cancers. British Journal of Cancer, 122(3), 306–314. Web.
Wang, R., Pan, W., Jin, L., Huang, W., Li, Y., Wu, D., Gao, C., Ma, D., & Liao, S. (2020). Human papillomavirus vaccine against cervical cancer: Opportunity and challenge. Cancer Letters, 471, 88–102. Web.