Cervical intraepithelial neoplasia (CIN) Flashcards
Gynaecological and Testicular pathology
The endocervix is lined by
columna (glandular) epithelium
The ectocervix is lined by
squamous epithelium
where do the endo and exocervix cell types meet in the cervix?
They meet at the squamoucolumnar junction.
What happens to the cervix during puberty and pregnancy?
Hormonally-induced eversion of the cervix occurs: The lower pH of the vagina results in the formation of a physiological transformation zone (TZ)
- The columnar epithelium undergoes physiological metaplasia to tougher and more resistant squamous epithelium.
Where does cervical dysplasia arise and why?
Cells undergoing metaplasia are predisposed to develop dysplasia, and so it is in the transformation zone that virtually all cervical dysplasia arises. In the cervix, the agent inducing dysplasia is HPV.
What is Cervical intraepithelial neoplasia?
Dysplasia occurring in the cervix. It is normally asymptomatic.
If left untreated what can Cervical intraepithelial neoplasia develop into?
Invasive squamous cell carcinoma
Give an example of the metaplasia-dysplasia-carcinoma sequence in relation to CIN.
columnar mucosa (vaginal acid metaplasia)-> metaplastic squamous mucosa -> (PERSISTENT high risk HPV infection)–> CIN (pre cancer) -> Squamous cell carcinoma (cancer)
What are the risk factors for developing CIN?
*Major risk factor = persistent high risk HPV infection.
High risk HPV 16 and 18 account for about 70% of cervical cancers.
HPV is sexually transmitted.
Low risk HPV 6 and 11 are associated with anogenital warts (condyloma acuminata) but NOT CIN and cervical cancer.
What is HPV - what type of infection is it?
Most HPV infections are transient, persistent infection (defined by the presence of HPV for more than 2 years) occurs in about 20% of infections with a high risk subtype.
How does the HPV cause its effects?
HPV viral DNA integrates into host cell DNA in the cervical squamous epithelium. the virus preferentially infects cels in the TZ since these cells are undergoing metaplasia and altered gene expression.
The viral E6 and E7 products interact with and inhibit tumour suppressor gene products, p53 and retinoblastoma protein (RB), respectively. These proteins are important for cell cycle control and apoptosis. Inactivation of these genes, which occur with high risk HPV infection, can include uncontrolled cell proliferation. High risk HPV infection is a prerequisite for cervical cancer but only a small proportion of HPV infections progress to either high grade CIN or cancer. Progression to malignancy requires one or more cofactors e.g. smoking, immunosuppression.
