Gynaecopathology - HPV Flashcards
What is the most common cancer associated with HPV
Cervical squamous cell carcinoma
What are HeLa cells
These are immortal adenocarcinoma cells of the cervix associated with the exposure to HPV
What are the etiopathogenetic factors of cancer:
1) infections in the cervix
2) Hormonal dysregulation in the uterus
3) Genetic abnormalities in the ovaries and the fallopian tubes
What are the concerns with tumours being found in the uterus
-Spreading into the serosa which can then spread into the abdominal cavity
What are the concerns with tumours being found in the cervix
It would spread up into the uterus as well as to the sides where is soft tissue and lymph nodes, anteriorly to the bladder and posteriorly to the rectum.
What is the Mullerian duct
It is involved in the development of the fallopian tube, uterus and cervix
What is the Mesonephric duct
It is inovlved in the development of male internal genital area.
Depending on the XX or XY combination of the chromosomes, there will be development of one of the ducts.
In males, anti-mullerian hormone (AMH) secreted from the Sertoli cells causes mullerian duct regression, allowing mesonephric structures to form the male reproductive tract
What happens to the duct that does not develop
It will persist to some degree within the foetus
The mullerian duct will fuse inferiorly to form the uterus and then will fuse even lower down with the urogenital sinus to create the cervix-vagina junction.
What happens when there is a uterus that does not have complete fusion of the two ducts
It would cause the formation of a septum. There would be a fibrotic band between resulting in a didelphys uterus which looks like two cavities on the right and the left
What is the cervix
It is the neck of the uterus, it has a glandular epithelium making mucin.
What is in the endocervix
In the cervical canal there is a single layer of glandular cells
What is in the exocervix
There is squamous epithelium which is the same as the cells that are found in the vagina.
What is the transition zone
It is found between the the single layer of epithelium and the squamous cell epithelium
There is a transition from the neck of the endocervical canal into the exocervix.
This is where squamous metaplasia can occur - sometimes incomplete metaplasia
What is the issue with squamous metaplasia
It is an area that is vulnerable to infection such as HPV infection
What is assessed when taking a cytology sample for a PAP test
The damage at the level of cervical mucosa - it would be detecting for the presence of both glandular cells and squamous cells
What is HPV
Human Papilloma Virus
Has circular dsDNA including 300 different genotypes
They can act at different epithelial sites: cutaneous and mucosa (transformation zones)
It can trigger both low risk HPV and high risk HPV neoplastic changes
What is the low risk HPV
Condyloma - a genital wart that grows more exophytic but they are not neoplastic
What is high risk HPV
1) CIN dysplasia - Cervical Intraepithelial neoplasia
2) High grade CIN dysplasia
3) Invasive cancer
4) Metastasis
What does low risk HPV do
HPV Type 6 and 11
Retains their DNA episome form
1) It exists in the cell nucleus in a circular episome - does not blend with the host DNA
2) If the viral genome is intact, new infectious viral particles can be produced; their presence in the cell is indicated by a perinuclear clearing (halo around the nucleus) or koilocytosis
It can be seen in a wart like lesion or in low grade CIN but can regress
What does high risk HPV do
High-risk HPV types (e.g., 16, 18) integrate their DNA into the host genome, leading to overexpression of the viral oncoproteins E6 and E7.
E6 promotes degradation of p53, impairing DNA damage response and apoptosis.
E7 inactivates Rb, disrupting cell cycle control and allowing uncontrolled proliferation.
Although viral integration leads to loss of genes needed for full viral replication, the persistent expression of E6 and E7 drives genomic instability and carcinogenesis, especially in cervical epithelial cells.
How does the host immune system play a role in this infection
Since this dysplasia can take a number of years to establish, the host immune system can potentially recognise and eliminate these cells.
How is the screening programme organised
In a way that will detect atypia in the presence of viral integration in the host cell.
If atypia is not detected, there will be a follow up after a certain period of time.
When does the atypia become a serious case
Cervical atypia becomes clinically significant when it progresses to high-grade lesions
High-grade squamous intraepithelial lesion (HSIL) suggests persistent infection and a higher risk of progression to cervical cancer.
Persistent high-risk HPV infection and detection of HSIL or CIN 2/3 on biopsy, are considered serious and typically warrant colposcopy.
What does a normal cervical histology slide look like
There would be a normal squamous epithelium with the basal layer having very small cells with round nuclei.
There would be a very high nucleo-cytoplasmic ration
There would be mitosis occurring
The layers closer to the surface:
- cells become larger
- more keratin is present
- pinker in colour the histology sample is
- maturation is seen
