Carcinogenesis Associated with Human Papillomavirus Infection. Mechanisms and Potential for Immunotherapy

Abstract

Human papillomavirus (HPV) infection is responsible for approximately 5% of all cancers and is associated with 30% of all pathogen related cancers. Cervical cancer is the third most common cancer in women worldwide; about 70% of cervical cancer cases are caused by the high risk HPVs (HR HPVs) of genotypes 16 and 18. HPV infection occurs mainly through sexual contact; however, viral transmission via horizontal and vertical pathways is also possible. After HPV infec tion of basal keratinocytes or ecto endocervical transition zone cells, viral DNA persists in the episomal form. In most cases, infected cells are eliminated by the immune system. Occasionally, elimination fails, and HPV infection becomes chronic. Replication of HPVs in dividing epithelial cells is accompanied by increased expression of the E6 and E7 oncoproteins. These oncoproteins are responsible for genomic instability, disruption of the cell cycle, cell proliferation, immortalization, and malignant transformation of HPV infected cells. Besides, E6 and E7 oncoproteins induce immunosuppression, pre venting the detection of HPV infected and transformed cells by the immune system. HPV integration into the genome of the host cell leads to the upregulation of E6 and E7 expression and contributes to HPV associated malignization. Prophylactic HPV vaccines can prevent over 80% of HPV associated anogenital cancers. The vaccine elicits immune response that prevents initial infection with a given HPV type but does not eliminate persistent virus once infection has occurred and does not prevent development of the HPV associated neoplasias, which necessitates the development of ther apeutic vaccines to treat chronic HPV infections and HPV associated malignancies.

Male papillomavirus infection and genotyping in the Qingyuan area

“…Among the 567 HPV-infected subjects, the single HPVtype infection was dominant (56.61%) and significantly higher than that of the double infection (26.63%) and multiple infection (16.75%). HPV6 and HPV11 were most common HPV subtypes.Although HPV6 and/or HPV11 are mostly latent infections in the genitalia and usually do not show clinical symptoms, these are the dominant genotypes that cause condyloma acuminata in countries around the world [10][11][12][13]. The high-risk subtypes of HPV play an important role in the development of penis cancer [11].…”

Human Papillomavirus Genotyping as a Tool for Cervical Cancer Prevention: From Commercially Available Human Papillomavirus DNA Test to Next-Generation Sequencing

“…After the infection, HPV can integrate into the human genome. The E2 protein loses part of its region and also its function, by controlling E6 and E7 genes during HPV genome replication [ 28 ]. The E6 and E7 oncogenes modulate important signaling pathways – from the host cells cell cycle, to apoptosis and immortalization – allowing viral replication and persistence and becoming the only viral genes that are always retained in cancer cells [ 29 , 30 ].…”

Human papillomavirus infection and follow-up on positive results in 7222 female samples obtained from 2016 to 2019 in Hefei, China

“…HPV 16 and 18 cause 70% of cervical cancers and precancerous cervical lesions. Non-carcinogenic HPV types (especially 6 and 11) can cause condyloma acuminatum and papillomatosis of the respiratory tract ( Harden & Munger, 2017 ; Vonsky et al, 2019 ).…”