Cervical HPV, dysplasia and carcinoma Flashcards
Describe the different histological grading of precancerous cervical squamous lesions?
HPV
CIN1
CIN2
CIN3
Describe the different cytological grading of precancerous cervical squamous lesions?
Low grade squamous intraepithelial lesion
High grade squamous intraepithelial lesion
Where does HPV complete its infectious cycle?
In differentiated squamous epithelium
Describe the human papillomavirus?
Capsid encompassing DNA
Early and late genes
What do the early and late genes encode for in HPV?
Early genes code for replication, proliferation and viral release
Late genes code for capsid
Describe how HPV gains access to human cells?
Pre-exisiting damage to epithelium > HPV enters > gains access to basement membrane > capsid contact > enters cells > differentiation > release for re-infection
Describe the importance of HPV episomal DNA?
HPV DNA can be episomal or integrate into host DNA
Episomal DNA associated with latent disease
HPV genetic material replicated in nucleus of infected cell in form of episome, then amplified to high copy numbers
Describe how episomal HPV DNA can become integrated into host DNA?
At some point, break in E2 > integration
Describe the function of E2, E6 and E7 in HPV?
E2: encodes for transcription function that suppresses E6 and E7
E6 binds p53 > TSG deactivated
E7 binds Rb gene > TSG deactivated
Describe how HPV causes cell proliferation?
Break in E2 > loss of regulation of E6 and E7
E6 binds p53 > TSG deactivated
E7 binds Rb gene > TSG deactivated
Uncontrolled proliferation
Which cells are most susceptible to HPV infection?
Cells at transformation zone (ectocervical-endocervical junction)
What is a cervical condyloma?
Large exophytic lesion
Thickened squamous epithelium
Describe a flat condyloma?
Flat lesion
Koilocytes present
Haphazard arrangement
Enlarged nuclei
Describe a CIN1 lesion?
Atypical chnages to lower 1/3 of epithelium
Describe a CIN2 lesion?
Atypical changes to lower 2/3 of epithelium
High grade lesion
Describe a CIN3 lesion?
Changes to greater than 2/3 of the epithelium/full thickness change
High grade lesion
Describe the risks associated with CIN2 and CIN3 lesions?
High chance of progressing to squamous cell carcinoma or adenocarcinoma
Describe a low grade squamous intraepithelial lesion?
Encompasses both HPV and CIN1 or both
Koliocytes
Describe koilocytes?
Binucleated
Cytoplasmic clearing
Hyperchromatic nuclei
Irregular
Describe a high grade squamous intraepithelial lesion?
Encompasses CIN2 and CIN3
More significant atypia
What is adenocarcinoma in situ?
Precursor to adenocarcinoma
Forms glandular structures on pap smear, nuclear atypia more significant
Describe the cytological appearrance of carcinoma?
Necrotic debris in background
High degree of cytological atypia
