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