Cervical neoplasia 3 Flashcards
What can specifically high risk HPV infections do?
Insert their DNA into the host cell DNA
Which gene is interrupted when HPV DNA is inserted into the host genome?
E2
Role of E2 gene?
Regulates E6 and E7 function
Effect of loss of E2 function?
Unregulated E6 and E7 transcription
What does E6 bind to?
p53
What does E7 bind to?
retinoblastoma protein
Effect of E7 binding retinoblastoma protein?
E2F is detached from retinoblastoma protein, leading to cell cycle activation and proliferation
Overall effects of HPV inserting into host DNA?
Cell cycle dysregulation, cell proliferation and progressive genetic mutations
How are cells observed to see if they have been infected with HPV?
They are scraped from the surface of the cervix, put onto a glass slide and stained
Name of smear technique for observing HPV cells?
Papanicolaou smear
How is cervical screening done currently?
Brush rotated in cervix–> placed in solution and sent to lab–> put on 2 machines to look for high risk HPV
What if the first cervical screen comes back +ve?
Glass slide method is done to look for physiological changes
Benefit of primary HPV screening over cytology screening?
Increased sensitivity for detecting cervical lesions
Negative predictive value of primary HPV screening?
93-99%
What happens if you have a high grade change or a persistent low grade change?
You are referred to colposcopy
What is colposcopy?
A diagnostic procedure using a microscope to get a magnified view of the cervix
What is the role of acetic acid and iodine in colposcopies?
Highlighting abnormal areas for improved ID
What is a LLETZ?
large loop excision of transformation zone
What does acetowhite do?
highlights abnormal cells
Size of diagnostic biopsies?
2-3mm of tissue
What happens if a CIN 1 (low grade abnormality) is observed during a diagnostic biopsy?
clinical follow-up (6-12 months)
What happens if a CIN 2+ (high grade abnormality) is observed during a diagnostic biopsy?
threshold for treatment (chance of regression versus risk of progression to invasive cancer)
What happens if squamous cell carcinoma is observed during a diagnostic biopsy?
radiological staging +/- surgery, chemotherapy and radiotherapy
What is immunohistochemistry?
Using antibodies to highlight protein expression within cells
What is used as a surrogate marker of HPV infection in cervical biopsies?
p16
What is p16?
tumour suppressor protein
How does p16 affect retinoblastoma protein?
p16 inhibits retinoblastoma protein’s phosphorylation
What drives increased p16 expression in the host cell?
Inactivation of retinoblastoma protein by E7
What can cause absent or patch p16 expression?
an inflammatory change
What can cause a strong block of p16 to appear?
High risk HPV infection
Makeup of the HPV vaccine?
Empty protein shell containing capsid proteins
Current HPV vaccine targets?
Nonavalent–> 6, 11, 16, 18, 31, 33, 45, 52, 58
