HPV cancer development
HPV are known to play a significant role in the development of certain types of cancer. Persistent infection with high-risk HPV types, particularly HPV16 and HPV18, is strongly associated with the development of cervical, anal, penile, vaginal, vulvar, and oropharyngeal cancers.18,45,29,45-48
During persistent infection, the HPV genome can integrate into the host cell’s DNA. Integration disrupts the viral life cycle and alters the expression of viral genes. Integration often occurs in regions of the viral genome that encode the E6 and E7 oncoproteins (Aksoy et al., 2017). The E6 oncoprotein of high-risk HPV types has several functions that contribute to cancer development. E6 binds to and degrades the p53 tumor suppressor protein, which is involved in cell cycle regulation, DNA repair, and apoptosis. Loss of p53 function allows infected cells with damaged DNA to survive and proliferate.12,43,46-48 The E7 oncoprotein of high-risk HPV types interacts with and inactivates the retinoblastoma (Rb) tumor suppressor protein. Rb normally prevents cell cycle progression from G1 to S phase. Inactivation of Rb by E7 disrupts cell cycle regulation and promotes uncontrolled cell proliferation.12,43,47,48
The combined effects of E6 and E7 oncoproteins can lead to cell transformation, characterized by uncontrolled cell growth and the formation of precancerous lesions. Infected cells lose their ability to undergo normal differentiation and acquire genetic and epigenetic alterations that contribute to malignant progression.43,48-50 HPV oncoproteins can interact with various host cell factors and signaling pathways, promoting cell survival, proliferation, and immune evasion. For example, E6 and E7 can modulate the activities of cellular proteins involved in DNA repair, apoptosis, cell adhesion, and immune response.2,19,20,40,43,44
HPV infection triggers an immune response, including the recruitment of immune cells to the site of infection. However, high-risk HPV types have developed mechanisms to evade immune detection and clearance. Persistent infection can lead to chronic inflammation, which promotes the survival and growth of infected cells and contributes to cancer development (Figure 2 ).2,44,43,48
HPV-associated precancerous lesions, such as cervical intraepithelial neoplasia (CIN), can progress to invasive cancer if left untreated. The accumulation of additional genetic alterations, such as mutations in tumor suppressor genes or activation of oncogenes, can drive the progression from premalignant lesions to invasive cancer.12,29,46-48