Cervical Cancer

Question 1

Approximately how many women are diagnosed with cervical cancer per year in the UK? Approximately how many die from the disease?

Answer 1

Approximately 2000 women are diagnosed with cervical cancer per year in the UK. Less than 1000 die from the disease.

Question 2

Squamous cell carcinoma accounts for ___ of cervical cancer cases and adenocarcinoma accounts for ___.

Answer 2

Squamous cell carcinoma accounts for more than 75% of cervical cancer cases and adenocarcinoma accounts for 25% of cases.

Question 3

What is the main risk cancer for cervical cancer?

Answer 3

HPV.

Question 4

What are the risk factors for HPV?

Answer 4

1) . High numbers of sexual partners
2) . High risk male partner
3) . Smoking
4) . Long-term use of oral contraceptives
5) . Early age of onset if first intercourse
6) . Early pregnancy
7) . Immunocompromised (HIV)
8) . Other STD’s eg. Chlamydia and Herpes

Question 5

Why is early age of intercourse/pregnancy a risk factor for cervical cancer?

Answer 5

Early age of first intercourse/pregnancy is relevant because of the position of the transformation zone. Eversion of the endocervical epithelium enables easier access to the basal layer of the epithelium.

Question 6

What is the most important risk factor for acquiring HPV?

Answer 6

Sexual behaviour. In women who have first intercourse aged 14-15 years the risk of cervical cancer is two-fold compared to women aged 20+.

The number of sexual partners is a factor and whether they have had multiple sexual partners.

There have been many studies that have shown that sexual behaviour is the most important risk factor for acquiring HPV.

Question 7

Why is smoking a risk factor for acquiring HPV?

Answer 7

Research suggests that smoking leads to an increased risk of cervical cancer.

Benzoapyrene (BaP) which is a cigarette carcinogen has been found in cervical mucus.

BaP could enhance viral persistence in the cells so that there is an increased risk of cervical cancer.

Question 8

What other virus apart from HPV is implicated with an increased risk of cervical cancer?

Answer 8

Herpes Simplex 2 is a virus that has been implicated in cervical cancer. The virus participates as a cofactor along with HPV.

Herpes Simplex 2 only has a modest effect on the risk of cervical cancer compared to HPV which has a strong effect.

Question 9

What type of cervical cancer has Chlamydia Trachomatis been implicated with?

Answer 9

Chlamydia Trachomatis has been indicated as a cofactor associated with squamous cell carcinoma if the cervix but not with other cervical cancers.

Question 10

Why is HIV a risk factor for cervical cancer?

Answer 10

HIV is a risk factor in cervical cancer because an immunosuppressed woman would not be able to fight off any HPV infection. Women who have advanced immunosuppression are more vulnerable to high risk types of HPV.

Question 11

How many different types of HPV are there?

Answer 11

More than 100.

Question 12

Which types of HPV are high risk and therefore associated with high grade cervical intraepithelial neoplasia (CIN), invasive squamous cell carcinoma of the cervix, and cervical adenocarcinoma?

Answer 12

HPV types 16, 18, 31, 33 and 45.

Question 13

How does HPV usually infect the cervix?

Answer 13

HPV usually infects the basal layer due to a very slight abrasion in the cervix. Most HPV infections are cleared by the immune system but long term persistence of the virus is a factor in the development of the disease.

Question 14

What genes does HPV cause the expression of?

Answer 14

HPV causes the expression of E6 and E7 genes.

Question 15

What do the E6 and E7 genes which are expressed as a result of HPV infection do?

Answer 15

E6 binds to and inhibits p53 (the protein product of a tumour suppressor gene) causing uncontrolled progression through the cell cycle.

E7 binds Rb. Rb is a tumour suppressor protein that is usually free to bind the E2F transcription factor thus preventing excess E2F from causing uncontrolled cell cycle progression. When E7 binds Rb, E2F remains unbound and results in uncontrolled cell cycle progression.

Question 16

HPV has a ________ and __________ phase in its life cycle.

Answer 16

HPV has a latent and productive phase in its life cycle.

Question 17

What are the 5 possible results of a cervical smear?

Answer 17

1) . Borderline nuclear changes
2) . Mild dyskaryosis
3) . Moderate dyskaryosis
4) . Severe dyskaryosis
5) . Glandular neoplasia

Question 18

How would you deal with a patient that showed borderline nuclear changes?

Answer 18

Repeat the smear in 6 months.

Not more than 3 borderline smears 6 months apart or 3 abnormal smears in 10 years.

HPV triage.

Question 19

How would you deal with a patient that had moderate dyskaryosis, severe dyskaryosis or glandular neoplasia?

Answer 19

Refer them for colposcopy.

Question 20

Describe a cervical punch biopsy.

Answer 20

A woman will first be microscopically examined by colposcopy.

If any abnormal area is found then a punch biopsy is taken using punch biopsy forceps.

This is a superficial biopsy (3mm max).

Question 21

Describe the process of a LLETZ.

Answer 21

Depending on the results of a cervical punch biopsy the next step may be to take a LLETZ. This can be performed in a colposcopy outpatients clinic under local anaesthesia.

A low voltage electric current is delivered via a thin wire that is passed through the tissue. It is used to cut away abnormal tissue. A thin layer of normal looking tissue may also be removed to ensure complete excision. The healing process may also get rid of residual abnormal tissue if it is scanty. The abnormal tissue is examined in histo.

Colposcopy prior to LLETZ involves the application of acetic acid to visualise a reticular delicate vascular pattern.

The depth of the specimen is very important. You want 8mm depth with clear margins.

Question 22

Describe a cold knife core biopsy.

Answer 22

Cold knife core biopsies are now decreasing in frequency. They require a fully equipped theatre.

This method is mostly used for micro invasive carcinoma where CIN3 is present at the margins or there is some glandular neoplasia.

Biopsy may be a depth of 1.2-2cm. This goes deep enough to compromise the internal OS of the cervix. Therefore there is a risk to future pregnancies and a bleeding issue.

Question 23

What does a hysterectomy involve and when may it be carried out?

Answer 23

A hysterectomy may be carried out when a woman has repeated abnormalities and has already completed her family.

It involves the removal of the uterine corpus, uterine cervix and possibly the upper part of the vagina. If the woman is premenopausal they leave the ovaries, otherwise a complete abdominal hysterectomy will be carried out.

If there is invasive cancer of a certain measurement then a procedure called a radical hysterectomy may be carried out which includes the removal of the upper third of the vagina and the ligaments including vessels and lymph nodes.

Question 24

If there is invasive cervical cancer exceeding a certain measurement what procedure may be carried out?

Answer 24

If there is invasive cancer of a certain measurement then a procedure called a radical hysterectomy may be carried out which includes the removal of the upper third of the vagina and the ligaments including vessels and lymph nodes.

Question 25

How can a radical hysterectomy be adapted for use in younger women?

Answer 25

A radical hysterectomy can be adapted to a procedure called a Trachelectomy in younger women.

This involves removing the cervix, upper third of the vagina, and the ligaments and vessels, but leaving the uterine body behind. This compromises the internal OS but pregnancy is possible.

Trachelectomy is the suggested treatment for women less than 40 years old. It is a fertility sparing procedure. It is only carried out for stage 1A2 and rarely for small volume stage 1B.

Question 26

If a patient displayed a smear with borderline nuclear changes for the first time what might you recommend?

Answer 26

HPV triage. If low risk HPV is identified then a repeat smear should be carried out in 6 months. If high risk HPV is identified then patient should be referred to colposcopy.

Question 27

If a patient displayed borderline nuclear changes in a smear for the third time what might you recommend?

Answer 27

Referral to colposcopy.

Question 28

Look at the clinical decisions following histology results on LETS flow diagrams.

Answer 28

See diagrams.

Question 29

If a patient is found to have SCC at more than stage 1a what would you recommend?

Answer 29

A radical hysterectomy, or Trachelectomy if fertility is an issue.

Question 30

If after a LLETZ a patient is found to have stage 1a adenocarcinoma what would you recommend?

Answer 30

Consider a hysterectomy.

Question 31

If after a LLETZ a patient is found to have more than stage 1a adenocarcinoma what would you recommend?

Answer 31

Radical hysterectomy, Trachelectomy if fertility is an issue.

Question 32

How can we treat HPV?

Answer 32

There is no cure for HPV. In most cases the immune system deals with it.

HPV shows a field effect due to integration.

If repeated borderline nuclear changes are found the patient should be put through to HPV triage.

Question 33

What is the importance of excisional margins?

Answer 33

Treatment is based on assessment of the excisional margins. Therefore slicing and embedding accurately is essential.

The ectocervical, endocervical and deep margins are all very important in assessing the completeness of excision.

Question 34

If a patient has borderline changes or mild dyskaryosis and is HPV negative what would you recommend for them?

Answer 34

They should be put back on to routine recall.

Question 35

If a patient has borderline changes or mild dyskaryosis and is HPV positive what would you recommend for them?

Answer 35

The should be referred for colposcopy.

Question 36

If a patient has been referred to colposcopy for borderline or low grade changes because they are HPV positive, and the colposcopy is negative, there is no biopsy needed, or there is a biopsy with no CIN what would you recommend?

Answer 36

They should be put back on normal recall.

Question 37

If a patient is found to have CIN1 at colposcopy what are the two possible recommendations?

Answer 37

Either choose not to treat and review the cytology (with or without colposcopy) at 12 months, or choose to treat then review the cytology after 6 months.

Question 38

What should you recommend for a patient that is found to be CIN2/3 at colposcopy?

Answer 38

They should be referred for treatment and the cytology should be reviewed after 6 months.

Question 39

If a patient presents with moderate dyskaryosis or worse but has already been treated for CIN what course of action would you recommend?

Answer 39

Review the cytology after 6 months.

Question 40

If a patient presents with moderate or severe dyskaryosis at a 6 month cytology review after having previous treatment for CIN what course of action should be taken?

Answer 40

They should be referred to colposcopy and treated, or if normal should be given cytology follow up according to national guidelines.

Question 41

If a patient presents with a normal, borderline, or mild smear at a 6 month cytology review after previous treatment for CIN what is recommended procedure?

Answer 41

HPV Test of Cure.

If negative put on 3 year recall.

If positive send to colposcopy and then treat if required, or if normal, cytology follow up according to national guidelines.

Question 42

Cervical cancer is the ___ most common cancer globally.

Answer 42

Cervical cancer is the 2nd most common cancer globally.