Cervical screening

Question 1

Which virus can result in CIN and cervical cancer?

Answer 1

Human papillomavirus (HPV)

Question 2

Why does the prevalence of HPV infection decline with age after peak at 15-25?

Answer 2

• Clearance of the virus by host immune system
• Less likely to acquire a new infection

Question 3

What other cancers can HPV cause?

Answer 3

• Anal cancer - 90%
• Penis - 40%
• Vulva/vagina - 40%
• Some head and neck cancers too

Question 4

Which layer of cells does the HPV invade in the epithelium?

Answer 4

Basal cells - they can stay here for several years with no ill effects but the woman is a carrier and therefore a potential spreader of the disease

Cancer - break through basement membrane

Question 5

What is required in the cervical lining in order for HPV to invade?

Answer 5

There needs to be a break in the skin (a micro-abrasion) which can be as small as 40 cells deep.

Question 6

What is picked up in a smear test?

Answer 6

An abnormal growth of squamous cells detectable on smear is called a squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN). Such changes may be low grade or high grade, depending on how much of the cervical epithelium is affected, and how abnormal the cells appear.

Question 7

Abnormal cells in the cervix that are graded from 1-3 according to what?

Answer 7

The proportion of cervix affected. These are pre-cancerous and so have the potential to progress to cancer.

Question 8

What are the most oncogenic types of HPV?

Answer 8

HPV 16 and 18

More likely to cause persistent infection + increases risk of developing High grade CIN and (more rarely) cancer

Question 9

What is the primary prevention of HPV?

Answer 9

HPV immunisation against HPV 16/18

2 dose regime given to 12-13 year olds Now given to girls and boys

Question 10

Look

Answer 10

• Most HPV infections are cleared by the immune system.
• It rarely causes cancer
• Most cervical cancers are associated with HPV

Question 11

What is the secondary prevention of HPV infection?

Answer 11

Cervical screening - smear test + HPV testing from that sample

Question 12

What puts you at risk of cervical cancer?

Answer 12

• HPV infection
• Immunodeficiency
• Herpes
• Smoking
• Age - The risk goes up between the late teens and mid-30s

Question 13

At what age are women in the UK first invited for a smear test as part of cervical cancer screening?

Answer 13

25

Question 14

In 2020 a change was made to how cervical screening is carried out. What changed and why?

Answer 14

The smear is taken in the same way, so the cervical sampling experience for women will not change.

• However, HPV testing is now used instead of cytology as it is more sensitive than cytology for high grade abnormalities.
• As more HPV-immunised women enter the screened population, cervical disease will decrease and will be more difficult to detect by cytology. HPV will be a more effective test for the future.

Question 15

How does HPV testing work?

Answer 15

• Molecular test on cervical cells.
• Done automatically by a machine that identifies the infection.
• Targets 14 High risk HPV types (but screening test does not identify specific HPV types)
• Uses hybridisation and PCR
• Could be transient HPV infection (body will fight it away) or CIN associated
• Very sensitive

Question 16

Is cytology still used?

Answer 16

Yes, but…

• First you test for high risk HPV with the sensitive HPV test.
• If hrHPV positive then use cytology on the same sample.
• Cytology identifies cellular changes.
• If there are abnormal cells detected cytology is used to work out whether it is:
  
  • Low grade - persisting infection/CIN1
  • High grade – CIN2/3. it is more specific

Question 17

When are women invited back if they get a negative hrHPV test?

Answer 17

Every 5 years

Question 18

What is the next step for women who have a positive hrHPV test?

Answer 18

Cytology

• If their cytology results are normal then they get another one in 1 year
• If abnormal cells are detected then refer to colposcopy

Question 19

What is a colposcopy?

Answer 19

• Examination of the cervix
• Aim to exclude obvious malignancy
• Use of acetic acid - this would cause whitening of any CIN lesions - identify them and the extent of the lesions so they can be treated

Question 20

Management options

Answer 20

Punch biopsy + histology to make a diagnosis - if it confirms CIN 2/3 then they will be treated

Question 21

How does HPV cause high grade CIN?

Answer 21

• Persistent infection
• Viral DNA integrates into host cell genome
• Overexpression of viral E6 and E7 proteins
• Deregulation of host cell cycle

Question 22

How is a CIN diagnosed?

Answer 22

Histology from biopsy

Question 23

What is CIN?

Answer 23

• Disorganised proliferation of abnormal cells in squamous epithelium (dysplasia)
  
  • i.e Lack of maturation, variation in cellular size and shape, nuclear enlargement, irregularity, hyperchromasia, cellular disarray
• CIN 1: tends to be HPV infection - low grade dysplasia–will regress
• CIN 2: moderate dysplasia – may regress
• CIN 3: severe dysplasia – unlikely to regress + Precursor of invasive cancer

Question 24

How is CIN 2/3 treated?

Answer 24

Excision or ablation (laser or thermal) of transformation zone of cervix

Question 25

Follow up after treatment of CIN

Answer 25

* Women are at an increased risk of cervical cancer after treatment of CIN compared with the normal population * Follow-up LBC (cervical sample - Liquid-based cytology) at 6 months for cytology and high risk HPV * If both negative – return to 3 year recall * Either positive – return to colposcopy

Question 26

Look

Answer 26

CIN 1-3 are all pre-cancerous they can then progress to cervical cancer

Question 27

Remember!!

Answer 27

* HPV is single most important cause of CIN and cervical cancer * Screening - cervical smear test - detects high risk HPV * Colposcopy + punch biopsy - detects pre-invasive changes which are asymptomatic * Screening allows treatment of pre-invasive changes (CIN) to prevent cancer - _early detection is key_ * HPV vaccination + cervical screening to maximise protection * Even if immunised, anyone with a cervix still needs to be offered cervical screening