Cervical Screening

Question 1

What does HPV stand for?

Answer 1

Human papillomavirus

Question 2

Does HPV mutate?

Answer 2

Stable virus which does not mutate

Question 3

What are the different types of HPV?

Answer 3

• Low risk types
  
  • 6, 11, 42, 44
  • Associated with genital warts and low grade CIN
  • Often transient and resolve
• High risk types
  
  • 16, 18, 31, 45
  • Persistent infection increases risk of developing high grade CIN and cancer
    
    • Due to viral DNA integrating into host genome, overexpression of viral E6 and E7 proteins causing deregulation of host cell cycle

Question 4

How does HPV increase risk of high grace CIN and ulcer?

Answer 4

• Persistent infection increases risk of developing high grade CIN and cancer
  
  • Due to viral DNA integrating into host genome, overexpression of viral E6 and E7 proteins causing deregulation of host cell cycle

Question 5

What proteins from HPV cause deregulation of host cell cycle?

Answer 5

E6 and E7 proteins

Question 6

Describe the epidemiology of HPV infections (lifetime exposure %, prevalence with age)?

Answer 6

• Lifetime exposure is 80%
• Prevalence declines with age
  
  • Peak prevalence 15-25 years
• Very common, most cleared by immune system

Question 7

In steps, describe the pathophysiology of HPV?

Answer 7

1. Transmitted by close contact, quite often through penetrative sex
2. Enters epithelial cells through minor abrasions/trauma
3. Replicates using host cellular mechanisms
4. Particles assembled in outer most layers of mature sites, decimating and releasing viral particle – not stimulating any immune response
5. Eventually, viral DNA becomes incorporated into host DNA causing disorganised cell replication
6. If not detected and treated early can invade basement membrane and become cancer due to E6 and E7 proteins causing deregulation of host cell cycle

Question 8

How is HPV transmitted?

Answer 8

1. Transmitted by close contact, quite often through penetrative sex

Question 9

What are possible complications of HPV?

Answer 9

Many cancers

Question 10

What percentage of cervix cancer is caused by HPV?

Answer 10

>99%

Question 11

What does CIN stand for?

Answer 11

Cervical intraepithelial neoplasia

Question 12

What is a CIN?

Answer 12

Is disorganised proliferation of abnormal cells in squamous epithelium (dysplasia):

• Lack of maturation
• Variation in cell size and shape
• Nuclear enlargement
• Irregularity
• Hyperchromasia
• Cellular disarray

Question 13

What are features seen in the histology for CIN?

Answer 13

• Lack of maturation
• Variation in cell size and shape
• Nuclear enlargement
• Irregularity
• Hyperchromasia
• Cellular disarray

Question 14

What are the different grades of CIN?

Answer 14

• CIN 1, low grade dysplasia
  
  • Will regress
• CIN 2, moderate dysplasia
  
  • May regress
• CIN 3, severe dysplasia
  
  • Unlikely to regress
  • Precursor of invasive cancer

Question 15

What is the treatment for CIN2/3?

Answer 15

• Excise transformation zone of cervix
• Ablate transformation zone of cervix
  
  • Thermal or laser
• Follow up after treatment
  
  • To confirm treatment was effective and to prevent invasive cancer
  • Follow up LBC at 6 months for cytology and high risk HPV
    
    • Both negative – return to 3 year recall
    • Either positive – return to colposcopy

Question 16

What follow up is done after treatment of CIN2/3?

Answer 16

• Follow up after treatment
  
  • To confirm treatment was effective and to prevent invasive cancer
  • Follow up LBC at 6 months for cytology and high risk HPV
    
    • Both negative – return to 3 year recall
    • Either positive – return to colposcopy

Question 17

Who gets HPV immunisation?

Answer 17

All girls and boys immunised against HPV 16/18/6/11:

• 12 to 13 year old children offered

Has massively reduced incidence of cervical cancer

Question 18

What is the aim of cervical screening?

Answer 18

• Reduce risk of cervical cancer by detecting cervical dyskaryosis and HPV

Question 19

What is the criteria to qualify for cervical screening?

Answer 19

• Person with cervix
• Aged 25-64
• 5 yearly smears

Question 20

How often do people who qualify get smears?

Answer 20

5 yearly

Question 21

What do cervical smears detect?

Answer 21

Smear detects abnormal growth of cells called squamous intraepithelial lesion (SIL):

• Can be low grade (LSIL) or high grade (HSIL) depending on how much of cervical epithelium is affected and how abnormal cells appear
• Taken from area between new squamo-columnar junction and old squamo-columnar junction (transformation zone)

Question 22

What are the different grades of SIL?

Answer 22

• Can be low grade (LSIL) or high grade (HSIL) depending on how much of cervical epithelium is affected and how abnormal cells appear

Question 23

What does SIL stand for?

Answer 23

Squamous intaepithelial lesion

Question 24

Where are cervical smears taken from?

Answer 24

• Taken from area between new squamo-columnar junction and old squamo-columnar junction (transformation zone)

Question 25

Compare and contrast HPV test and cytology?

Answer 25

Question 26

What happens if abnormal cells are detected from cervical smear?

Answer 26

* Biopsy and histological examination, where abnormal cells are classified as cervical intraepithelial neoplasia (CIN) which is graded from 1-3 by proportion of cervix affected * Grades 2 and 3 have the potential to progress to cancer

Question 27

What grades of CIN have potential to progress to cancer?

Answer 27

* Grades 2 and 3 have the potential to progress to cancer

Question 28

How are CINs graded?

Answer 28

By proportion of cervix affected

Question 29

Describe the management for a woman with postive smear result?

Answer 29

* Scottish cervical call recall system (SCCRS) sends letter to primary care to tell GPs who is due a smear and which ones are positive * Community health index (CHI) ensures correct patients (register of all patients in NHS Scotland) * If negative routine recall in 5 years time, if positive * Cytology normal, repeat in 1 year * If dyskaryosis refer to colposcopy * Microscopic assessment of cells scraped from transformation zone looking for abnormal cells (dyskaryosis) which indicates woman may have underlying cervical intraepithelial neoplasia (CIN) * Nuclear features of abnormal cells – increased size and nuclear:cytoplasmic ratio, variation in size, shape and coarse irregular chromatin, nucleoli visible * Koilocytes (also known as halo cells, type of epithelial cell that develops following HPV infection) reflects HPV infection * Graded low grade, borderline and high grade * First visit to colposcopy * Magnification and light to see cervix and exclude obvious malignancy * Use of acetic acid with iodine to identify limits of lesions, select biopsy site and define area to treat * Take punch biopsy of lesion * Pathologist looking if HPV infection, precancerous changes cervical intraepithelial neoplasia (CIN) or cervical carcinoma * If low grade, sent back to community for standard smears, if high grade management goes ahead (if CIN2/3)

Question 30

Who sends letters to GPs about who is due a smear?

Answer 30

Scottish cervical call recall system (SCCRS)