Cervical cancer & intraepithelial neoplasia

Question 1

Define cervical cancer & intraepithelial neoplasia.

Answer 1

Cervical cancer is a human papillomavirus-related malignancy of the uterine cervical mucosa.
Most commonly from metaplastic squamous cells in the transformation zone

Question 2

Explain aetiology of cervical cancer & intraepithelial neoplasia.

Answer 2

HPV detected in 99.7% squamous cell carcinomas + adenocarcinomas (most common types)

HPV-16 + 18 are the most common high-risk types.

Other high-risk types inc. 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, + 82.

Question 3

Describe the prevalence of HPV

Answer 3

Most sexually active adults will be exposed to HPV
Immune system clears the virus in 6 months in 50%, + 2y in 90%

Question 4

Summarise the epidemiology of cervical cancer & intraepithelial neoplasia.

Answer 4

4th most common malignancy in women worldwide.
50% occurs in <45y
Incidence rates in UK highest in 25-29y

Question 5

Give 8 risk factors for cervical cancer

Answer 5

Smoking
HIV
Persistent HPV infection
Early 1st intercourse
Many sexual partners
High parity
Low SES
COCP

Question 6

What are the 2 types of cervical cancer?

Answer 6

Squamous (80%)
Adenocarcinoma (20%)

Question 7

How does HPV cause cervical cancer?

Answer 7

HPV 16+18 produce the oncogenes E6 + E7 respectively
E6 inhibits p53 tumour suppressor gene
E7 inhibits RB suppressor gene

Question 8

How may cervical cancer present?

Answer 8

Routine cervical cancer screening
Abnormal PV bleeding, PCB, IMB, PMB
Discharge foul smelling/ bloody
Dyspareunia

Question 9

What investigations are required for cervical cancer?

Answer 9

Speculum: cervical mass +/- bleeding
Smear for hrHPV + cytology (abnormal cells)
Colposcopy
CTCAP
Discuss in MDT

Question 10

What is cervical intraepithelial neoplasia?

Answer 10

Premalignant epithelial dysplasia
CIN I: least invasive, ~1/3 of basal epithelium. Architecture mostly intact
CIN II: <2/3 basal epithelium, loss of architecture.
CIN III: Severe, irreversible, full thickness, carcinoma in situ

Question 11

What cells are pathogonomic for HPV infection, which may be seen in CIN?

Answer 11

Koilocytes

Question 12

Describe the epithelial lining of the cervix

Answer 12

Ectocervix: squamous
Endocervix: glandular

Question 13

What are the initial investigations for cervical cancer?

Answer 13

Speculum: Cervical mass may be seen, cervical bleeding

Cytology: Look for HPV and then abnormal cells

CIN grading can be done after histology

Question 14

What is the management for cervical cancer & intraepithelial neoplasia?

Answer 14

CIN/ IA1: LLETZ or cone biopsy.
IA2-IB2: Radical TAH + BSO +/- chemo/ radio
IB3-IVA: radio + chemothrapy.
IV: Systemic chemo

Question 15

What are the complications of LLETZ and cone biopsies?

Answer 15

Cervical shortening can lead to cervical incompetence which can lead to mid trimester miscarriage + preterm labour

Question 16

Summarise the prognosis for patients with cervical cancer & intraepithelial neoplasia.

Answer 16

5y varies based on disease stage at diagnosis:

I: 92%
II-III: 56%
IV: 17%.

Question 17

When are smear tests offered?

Answer 17

25-49y: 3 yearly
50-64: 5 yearly
Best mid-cycle

Question 18

How are pregnant women advised regarding smear tests?

Answer 18

Delay smear until 3/12 postpartum unless missed screening or previous abnormality

Question 19

What is the treatment for CIN?

Answer 19

Large loop excision of transformation zone (LLETZ)
Cone biopsy (larger lesions)

Question 20

What are the stages of cervical cancer?

Answer 20

I: tumour confined to cervix
II: tumour invades beyond uterus, but not into pelvic wall or lower 1/3 vagina
III: Tumour invades pelvic wall +/- involves lower 1/3 vagina +/- causes hydronephrosis or non functioning kidney
IV: carcinoma extends beyond true pelvis/ involves mucosa of bladder/ rectum

Question 21

Which chemicals are applied during colposcopy for better visualisation?

Answer 21

Visual Inspection with Acetic Acid (VIA)
or
Visual Inspection with Lugol’s Iodine (VILI)

Question 22

How is visualisation with acetic acid performed?

Answer 22

Apply acetic acid to cervix

If cervical epithelium contains an abnormal load of cellular proteins, the acetic acid coagulates the proteins, giving the concerning area an opaque WHITE coating

“Acetowhite”

Question 23

What is Lugol’s iodine test also known as?

Answer 23

Schiller’s iodine test

Question 24

What is Lugol’s iodine test?

Answer 24

Apply iodine-based solution.
Iodine solution is glycophilic, normal glycogen containing squamous epithelium stains brown or black.
CIN + invasive cancer has little glycogen + does not stain. Columnar epithelium is also deficient in glycogen so does not stain

Question 25

Following visualisation on colposcopy, what may be done?

Answer 25

If area of abnormal cells is obvious, can have tx
right away (usually LLETZ). If not clear, may need biopsy +/- bring back for tx if required.