Cervical Screening

Question 1

12% of human cancers are caused by viruses. Which viruses are implicated?

Answer 1

• HBV
• HIV
• EBV
• HPV

Question 2

how common is HPV infection?

Answer 2

• very common
• lifetime risk of exposure 80% from serological studies
• peak prevalence 15-25 years, then declining with age
• 10% overall prevalence
• 30% prevalence in young women

Question 3

HPV causes other less common cancers, list these

Answer 3

• cervix (> 99% cases caused by HPV)
• penis 40%
• vulva/vagina 40%
• anus 90% (hiher rates in men who have sex with men)
• mouth 3%
• oropharynx 12%

Question 4

what is a squamous intraepithelial lesion (SIL)?

Answer 4

• an abnormal growth of squamous cells detectable on a smear.
• such changes may be low grade (LSIL) or high grade (HSIL), depending on how much of the cervical epithelium is affected, and how abnormal the cells appear.

Question 5

what is a cervical intraepithelial neoplasia (CIN)?

Answer 5

Abnormal cells in the cervix detected by biopsy and histological examination.
Graded 1-3 according to the proportion of cervix affected.

Question 6

which papilloma virus types are responsible for approx 70% of cervical cancers in Europe?

Answer 6

16 & 18

Question 7

describe the UK HPV immunisation programme

Answer 7

• 12 year old (girls and boys) receive a two dose regimen of a quadrivalent vaccine against HPV 16/18/6/11

Question 8

why did we change from cytology to HPV testing for cervical screening?

Answer 8

• HPV testing 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 more effective test for the future.
• If the HPV test is negative, the woman’s chance of developing cervical cancer in the next 5 years is very small, allowing a 5 year screening interval for all women regardless of age.
• if HPV test is positive, then cytology is performed.

Question 9

what are the nuclear features of abnormal cervical cells identified by cytology?

Answer 9

abnormal = dyskaryosis
- can be low-grade or high-grade

Nuclear features:
- increased size and nuclear:cytoplasmic ratio
- variation in shape, size
- coarse irregular chromatin
- nucleoli

Question 10

what happens next if a cytology identifies abnormal cervical cells (dyskaryosis)?

Answer 10

Refer to Colposcopy:
- magnification and light to see cervix
- exclude obvious malignancy
- use of acetic acid +/- iodene to identify limits of lesion, select biopsy site and define area to treat.

Question 11

Colposcopy options for management

Answer 11

• punch biopsy to make diagnosis
• return for treatment if biopsy CIN 2/3
• ‘see and treat’ at first visit if obvious high-grade lesion

Question 12

how does HPV target the transformation zone of the cervix?

squamo-columnar junction

Answer 12

• infects basal layer cells
• utilises host for replication
• as host cell matures, different viral genes are expressed, examples: E7 protein product - prevents cell cycle arrest, E6 protein product - inhibits cell death.

Question 13

describe Koilocytosis

Answer 13

• a feature of HPV histology
• cells with wrinkled nucleus and perinuclear halo
• multinucleation

Question 14

what are the low-risk types of human papilloma virus?

Answer 14

6, 11, 42, 44
- typically associated with genital warts and low-grade CIN
- often transient and resolve

Question 15

what are the high-risk types of HPV?

Answer 15

• 16,18, 31, 45
• peristent infection increases risk of developing high grade CIN and (more rarely) cancer

Question 16

how does HPV cause high grade CIN?

Answer 16

Persistent infection:
- viral DNA integrates into host cell genome
- overexpression of viral E6 and E7 proteins
- deregulation of host cell cycle

Question 17

what is considered a CIN3?

Answer 17

• Neoplastic cells or undifferentiated cells fill full thickness of epith here , no normal differentiated cells seen = CIN3

Question 18

what is considered a CIN2?

Answer 18

When undiffer cells occupy 2/3 of thickness and only top layers show maturation to medium size cells = CIN2

Question 19

what is considered a CIN1?

Answer 19

If undiff cells only occupy lowest 1/3 of epith and surface cells can mature to big flat cells = CIN1

Question 20

what is the treatment for CIN2/3?

Answer 20

• excise transformation zone TZ pf cervix: LLETZ
• ablate TZ of cervix: thermal or laser ablation

Question 21

what is the follow-up procedure after treatment of CIN?

Answer 21

• follow-up liquid based cytology (LBC) at 6 months for cytology and high-risk HPV
• both negative - return to 3-year recall
• either positive - return to colposcopy

Question 22

what is the aim of cervical screening?

Answer 22

reduce the risk of cervical cancer