HPV and cancer Flashcards
What is HPV?
Human papilloma virus (HPV) is a DNA virus that infects epithelial cells of the mucosa and the skin.
It is linked to cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers.
HPV life cycle involves binding to a host cell, integration of its genome into host DNA, its transcription, translation of viral mRNA, duplication of the HPV genome and packaging into a new virus particle.
What are the two categories of HPVs?
Low-risk HPVs:
Do not cause cancer but can cause skin warts on or around the genitals or anus. For example, HPV sub-types 6 and 11 cause 90 percent of all genital warts.
High-risk or oncogenic HPVs:
Can cause cancer. At least a dozen high-risk HPV types have been identified. Two of these, HPV sub-types 16 and 18, are responsible for the majority of HPV-caused
cancers.
How can HPV lead to cancer?
If the immune system does not supress or eliminate HPV and the infection becomes chronic and the HPV strain is high risk cancer can develop.
HPV infection of epithelial cells causes the expression of viral proteins E6 and E7.
These prevent tumour suppressor function leading to uncontrolled proliferation of the infected epithelial cell.
E6:
Binds to and promotes the degradation of p53 (p53 is responsible for senescence and apoptosis).
Decreases the cell cycle inhibitor p21.
Increases expression of cyclin E ./CDK2.
E7:
Binds to and inactivates pRB and disrupts the pRb-E2F complex (pRB induces senescence and responsible for the G1 checkpoint).
Increases the activity of CDK2.
This can lead to increased immortalisation and genomic instability and eventually tumour development.
How do you prevent cancer caused by HPV?
Vaccines are directed against the capsid protein L1 of HPV.
Vaccination helps prevent HPV infections but does not:
Eliminate existing HPV infections.
Treat cancer caused by high risk HPV stains.
What is the treatment for cervical cancer?
Treated with surgery and adjuvant cytotoxic chemotherapy aimed at blocking DNA replication and / or mitosis depending on the risk of reoccurrence.
Radiochemotherapy -radiation and cisplatin (low grade).
Cisplain / topotecan or cisplatin / paxlitaxel (metastatic) which could be given with bevacizumab.
