Cervical cancers

Question 1

Describe the anatomy of the cervix

Answer 1

Fibromuscular structure that sits at the lower portion of the uterus made from:
- internal OS (the opening between the cervix and the upper part of the uterus), the endocervix (the inner part of the cervix that forms the endocervical canal)
- ectocervix (the outer part of the cervix that opens into the vagina)
- external OS (the opening between the cervix and vagina).
- The area where the endocervix and ectocervix meet is called the squamocolumnar junction, which contains both glandular cells (column-shaped cells that make mucus) from the endocervix and squamous cells (thin, flat cells) from the ectocervix

Question 2

Which strands of HPV are commonly linked to cervical cancer? [2]

Answer 2

HPV 16 and HPV 18:
- considered the most significant risk factor; account for 70% of all cervical cancers

Question 3

What is an ectropion? [1]

Answer 3

Ectropion refers to the eversion of endocervical columnar epithelium onto the ectocervix.
- This is a normal physiological process that occurs at different stages of life (e.g. post menarche, during pregnancy)

Question 4

Name 5 risk factors for cervical cancer [5]

Answer 4

• Missed screening
• Smoking
• HPV Infection - increased by early and lots of sexual activity
• High parity (number of births at full term > 5)
• Family history
• Combined oral contraceptive
• Immunosuppression (e.g HIV/AIDS)

TOM TIP: When you are performing a history in your exams and considering cancer, always ask about risk factors to show your examiners you are assessing that patient’s risk of having cancer. Ask about attendance to smears, number of sexual partners, family history and smoking.

Question 5

The most common type of cervical cancer is []

Answer 5

The most common type of cervical cancer is squamous cell carcinoma.

Question 6

Describe the pathophysiology of cervical cancer [4]

Answer 6

1. HPV infection from HPV 16 and 18

2. HPV produces proteins E6 and E7; which inhibits the tumour suppressor genes P53 and pRb (E6 - P53; E7 - pRb); this initiates cell cycle progression

3. Cervical Intraepithelial Neoplasia (CIN) occurs (CIN1: self limiting; CIN2 & 3: can lead invasive carcinomas)

4. Can lead to invasion of malignant cells through the basement membrane into underlying stroma.

.

Question 7

Describe what the different CIN levels are [3]

Answer 7

CIN I: mild dysplasia, affecting 1/3 the thickness of the epithelial layer, likely to return to normal without treatment

CIN II: moderate dysplasia, affecting 2/3 the thickness of the epithelial layer, likely to progress to cancer if untreated

CIN III: severe dysplasia, very likely to progress to cancer if untreated

CIN III is sometimes called cervical carcinoma in situ.

TOM TIP: Try not to get mixed up between dysplasia found during colposcopy and dyskaryosis on smear results.

Question 8

Describe the screening process for cervical cancer

Answer 8

1. Perform a cervical smear (collecting cells from cervix)
- reviewed for the presence of high-risk HPV. If they are present, cytology will be completed.

2. Cytology is performed. Results can be classified as:
Borderline changes in endocervical cells:
- changes that don’t meet the criteria of other abnormalities. Patients should be referred and have a colposcopy within 2 weeks.

Borderline changes in squamous cells:
- changes that don’t meet the criteria of other abnormalities. Patients should be referred and offered a colposcopy within 6 weeks.

Low-grade dyskaryosis:
- dyskaryosis
refers to abnormal appearing cells. Low-grade dyskaryosis has a lower risk of invasive cancer. Patients should be referred and offered a colposcopy within 6 weeks.

High-grade dyskaryosis:
- may be moderate or severe, which tends to correlate with CIN 2 and CIN 3. Patients should be referred and have a colposcopy within 2 weeks.

Suspected invasive cancer:
- patients should be referred and have a colposcopy within 2 weeks.

Glandular neoplasia:
- patients should be referred and have a colposcopy within 2 weeks.

Question 9

When in cycle is best to take smear? [1]

Answer 9

It is said that the best time to take a cervical smear is around mid-cycle. Whilst there is limited evidence to support this it is still the current advice given out by the NHS.

Question 10

A summary of the management of smear results based on the Public Health England guidelines from 2019 is:
* Inadequate sample – repeat the smear after at least [] months
* HPV negative – []
* HPV positive with normal cytology – []
* HPV positive with abnormal cytology – []

Answer 10

• Inadequate sample – repeat the smear after at least three months
• HPV negative – continue routine screening
• HPV positive with normal cytology – repeat the HPV test after 12 months
• HPV positive with abnormal cytology – refer for colposcopy

Question 11

Describe what happens [1] & what tests [2] are performed when colposcopy occurs

Answer 11

Colposcopy is a procedure that allows optimal visualisation of the cervix.:
- As with the cervical smear a speculum is placed in the vaginal vault and the cervix identified.
- A colposcope (which remains external) is then used to offer a magnified view of the cervix

Tests:
- Schiller’s iodine test involves using an iodine solution to stain the cells of the cervix. Iodine will stain healthy cells a brown colour. Abnormal areas will not stain.
- Acetic acid causes abnormal cells to appear white. This appearance is described as acetowhite.
- A punch biopsy or large loop excision of the transformational zone can be performed during the colposcopy procedure to get a tissue sample.

Question 12

White cervical cells after staining in colposcopy would indicate which test has been performed? [1]

What would this indicate? [1]

Answer 12

Acetic acid causes abnormal cells to appear white. This appearance is described as acetowhite. This occurs in cells with an increased nuclear to cytoplasmic ratio (more nuclear material), such as cervical intraepithelial neoplasia and cervical cancer cells.

Question 13

What staining has been used on this cervix? [1]

Answer 13

Question 14

Which test / stain has been performed? [1]
What does this indicate? [1]

Answer 14

Schiller’s (Lugol’s) iodine test involves the application of an iodine-based solution. As the iodine solution is glycophilic, normal glycogen containing squamous epithelium stains brown or black
- CIN and invasive cancer has little glycogen and does not stain. Columnar epithelium is also deficient in glycogen so does not stain.

Question 15

Cervical screening may be temporarily delayed in a number of circumstances. Reasons to delay include: [4]

Answer 15

• Currently menstruating
• Abnormal vaginal discharge / pelvic infection
• Less than 12 weeks postnatal
• Less than 12 weeks after a termination of pregnancy or miscarriage

Question 16

Cervical screening:

In pregnant women normally a routine screen will often be rescheduled to [] months** post-partum**. If a woman has had an abnormal screen and subsequently falls pregnant, management should be guided by specialists.

Answer 16

3 months post-partum

Question 17

What considerations around post-hysterectomy screening need to be considered? [1]

Answer 17

Type of hysterectomy: total (cervix removed) versus subtotal (cervix remains):
- Patients who have undergone a total hysterectomy may need to continue screening depending on the presence of CIN because of the risk of developing vaginal intraepithelial neoplasia.
- Patients who have undergone a subtotal hysterectomy will need to continue on the National Cervical Screening Programme.

Question 18

What are the management plans for CIN 1-3? [3]

Answer 18

Patients with CIN 1 will typically be brought back for repeat review at 12 months.

CIN 2 may resolve but risk of cancer is increased and removal is typically indicated.

In CIN 3 removal is always advised.

Question 19

Describe what is meant by a cone biopsy [1] and when it is indicated []1

Answer 19

A cone biopsy is a treatment for cervical intraepithelial neoplasia (CIN) and very early-stage cervical cancer.:
- The surgeon removes a cone-shaped piece of the cervix using a scalpel
- This sample is sent for histology to assess for malignancy.

Question 20

Who is screened and how often? [2]

Answer 20

25-49 years:
- 3-yearly screening

50-64 years:
- 5-yearly screening

cervical screening cannot be offered to women over 64 (unlike breast screening, where patients can self-refer once past screening age)

Question 21

What are the clinical features of cervical cancer? [3]

Answer 21

Local Symptoms:
Vaginal Bleeding:
- may occur after sexual intercourse (post-coital), between menstrual periods (intermenstrual), or in post-menopausal women.

Vaginal Discharge:
- An abnormal discharge, often foul-smelling due to necrosis of tumour tissue, may be reported by patients.

Pelvic Pain:
- This may occur due to advanced local disease causing nerve invasion or obstruction of pelvic structures.

Dyspareunia (pain or discomfort with sex)

Question 22

How often are women with HIV screened? [1]

Answer 22

Women with HIV are screened annually

Question 23

Describe the different stages of cervical cancer [4]

Answer 23

Stage 1: Confined to the cervix
Stage 2: Invades the uterus or upper 2/3 of the vagina but not lower 1/3 or vagina
Stage 3: Invades the pelvic wall or lower 1/3 of the vagina
Stage 4: Invades the bladder, rectum or beyond the pelvis

Question 24

Management of cervical cancer depends on the stage and the individual situation. The usual treatments for CIN and early stage 1A is? [1]

Answer 24

Cervical intraepithelial neoplasia and early-stage 1A:
- LLETZ or cone biopsy

Question 25

Management of cervical cancer depends on the stage and the individual situation. The usual treatments for CIN and stage 1B-2A is? [2]

Answer 25

Stage 1B – 2A:
- Radical hysterectomy and removal of local lymph nodes with chemotherapy and radiotherapy

Question 26

Management of cervical cancer depends on the stage and the individual situation. The usual treatments for CIN and stage 2B-4A ? [1]

Answer 26

Stage 2B – 4A:
- Chemotherapy and radiotherapy
- Radiotherapy may either be bachytherapy or external beam radiotherapy
- Cisplatin is the commonly used chemotherapeutic agent

Question 27

Management of cervical cancer depends on the stage and the individual situation. The usual treatments for CIN and stage 4B ? [1]

Answer 27

Stage 4B: Management may involve a combination of surgery, radiotherapy, chemotherapy and palliative care

Question 28

Which MAB may be used in combination with some chemotherapies? [1]

What is its target? [1]

Answer 28

Bevacizumab (Avastin) is a monoclonal antibody that may be used in combination with other chemotherapies in the treatment of metastatic or recurrent cervical cancer. It is also used in several other types of cancer.

It targets vascular endothelial growth factor A (VEGF-A), which is responsible for the development of new blood vessels. Therefore, it reduces the development of new blood vessels. You may also come across this medication as a treatment for wet age-related macular degeneration, where it is injected directly into the patient eye to stop new blood vessels forming on the retina.

Question 29

HPV vaccine is given to kids.

Which strains cause genital warts [2]

Which strains caused cervical cancer? [2]

Answer 29

Strains 6 and 11 cause genital warts
Strains 16 and 18 cause cervical cancer

Question 30

TOM TIP: A common exam task is to counsel parents about their child receiving the HPV vaccine. They are upset because they believe this implies their daughter or son is sexually promiscuous.

How should you focus your discussion?

Answer 30

Focus on the fact it needs to be given before they become sexually active and that it protects them from cervical cancer and genital warts. HPV is very common and infection is the number one risk factor for cervical cancer.

Question 31

Describe complications that may arise due to cervical cancer to the urinary system [2] and bowel dysfunction [2]

Answer 31

Urinary Dysfunction: may arise from the local invasion of the tumour or as a consequence of treatment:
* Ureteral obstruction: Advanced cervical cancer can infiltrate the ureters, causing obstruction and hydronephrosis.
* Urinary incontinence and retention: Surgery and radiation therapy can damage nerves and muscles controlling urinary function, leading to urinary incontinence or retention.
* Vesicovaginal (bladder and vagina) fistula may occur

Cervical cancer and its treatments can also result in bowel dysfunction:
* Obstruction: Direct invasion of the tumour into the rectum, or radiation-induced fibrosis, can cause bowel obstruction.
* Radiation proctitis: Radiation therapy can induce inflammation and damage to the rectum, causing symptoms such as diarrhoea, urgency, and rectal bleeding.

Question 32

Answer 32

combined oral contraceptive pill use

Question 33

Answer 33

risk factors include: lower socioeconomic status

Question 34

Answer 34

First inadequate sample repeat smear within 3 months

Question 35

Answer 35

refer for colposcopy

Question 36

Answer 36

Two consecutive inadequate samples then refer for colposcopy

Question 37

Answer 37

all recent smears cytologically normal) return to routine recall

Question 38

For a 30-year-old female, what is the most appropriate action if the latest smear shows sample is hrHPV +ve + cytologically normal? [1]

Answer 38

Repeat in 12 months

Question 39

For a 30-year-old female, what is the most appropriate action if the latest smear shows sample is hrHPV +ve + cytologically abnormal?

Answer 39

Refer for colposcopy

Question 40

Which instances would you Refer for colposcopy? [3]

Answer 40

• 2nd repeat smear at 24 months is still hrHPV +ve (all recent smears cytologically normal)
• sample is hrHPV +ve + cytologically abnormal
• two consecutive inadequate samples then

Question 41

In which instances would you test again at 12 months? [1]

Answer 41