From the Guidelines
Human Papillomavirus (HPV) infection involves the virus entering the body through small breaks in the skin or mucous membranes, typically during sexual contact, and targets the basal layer of epithelial cells, where it integrates its DNA into the host cell's genome, using the host cell's machinery to replicate and produce viral proteins, as described in the study by 1. The pathophysiology of HPV is complex and involves several key steps:
- Initiation of infection in the basal layer of the epithelium, where the virus uses the cellular replication machinery to amplify its genome, as noted in the study by 1.
- Differentiating epithelial cells that are normally nondividing remain in an active cell cycle, leading to a thickened, sometimes exophytic, epithelial lesion, as described in the study by 1.
- The virus is released as cells exfoliate from the epithelium, allowing for transmission to other individuals, as mentioned in the study by 1.
- With neoplastic progression, the virus might integrate into the host chromosomes, and little virion production will occur, as noted in the study by 1. Key factors in the development of HPV-related diseases include:
- The type of HPV, with high-risk types (such as HPV 16 and 18) being more likely to cause cancer, as described in the study by 1.
- The persistence of infection, with longer-lasting infections being more likely to lead to cancer, as noted in the study by 1.
- The presence of other risk factors, such as smoking, immune suppression, and other sexually transmitted infections, as mentioned in the study by 1. The progression from HPV infection to cancer typically takes years or decades, which is why regular screening and vaccination before exposure are effective preventive strategies, as described in the study by 1.
From the Research
Pathophysiology of Human Papillomavirus (HPV)
The pathophysiology of HPV involves the infection of epithelial cells, which can lead to a range of benign lesions and malignant tumors. Key aspects of HPV pathophysiology include:
- Infection of basal epithelial cells, where the virus enters the nuclei and begins to replicate 2
- Strict tissue specificity for infection, with over 200 different HPV genotypes identified to date 2
- Ability to subvert cellular growth regulatory pathways and uncouple cellular proliferation and differentiation 3
HPV Replication Cycle
The HPV replication cycle is intimately linked to epithelial differentiation. Upon infection, the virus:
- Enters the nuclei of basal epithelial cells 2
- Begins to replicate, with a tightly orchestrated pattern of viral gene expression 2
- Triggers keratinocyte differentiation, allowing the virus to complete its replication cycle 2
Cancer Progression
Cancer progression is due to persistent infection with high-risk HPV (HR-HPV) types, such as HPV16 and HPV18. Key factors in cancer progression include:
- Increased expression of viral oncoproteins E6 and E7, which activate the cell cycle, inhibit apoptosis, and allow accumulation of DNA damage 2, 4, 5
- Inhibition of antioncogens, such as p53 and retinoblastoma, and interference with cyclins and cyclin-dependent kinases (cdks) 3
- Genetic instability and accumulation of mutations, leading to malignant transformation 4, 5
HPV-Associated Lesions
HPV-associated lesions can range from benign warts to malignant tumors, including:
- Cervical intraepithelial neoplasia (CIN), which can progress to invasive cervical cancer (ICC) 4
- Anogenital cancers, including vulval, vaginal, anal, and penile cancers 4
- Head and neck cancers, particularly oropharyngeal cancers 2, 4
Immune Response
The immune system plays a crucial role in clearing HPV infections, with most individuals experiencing transient HR-HPV infection that is eventually recognized and cleared by the immune system 2. However, in some cases, the virus can evade the immune system and persist, leading to cancer progression.