Cervix - benign and malignant disease and screening

Question 1

What are the high risk types of HPV?

Answer 1

16, 18, 33

(31, 45)

Question 2

How does HPV cause cervical cancer?

Answer 2

• Infects basal layer and utilitses host for replication
• Virus produces E6 + E7 protein product -> prevents cell cycle arrest and inhibits cell death

Question 3

Where do columnar cells of the endocarvix undergo metaplasia?

Answer 3

Transformation zone (squamocolumnar junction)

Question 4

What is post coital bleeding?

Answer 4

Vaginal bleeding occurring immediately after sexual intercourse – this has a 6% annual incidence in the UK

Question 5

What is intermenstrual bleeding?

Answer 5

Vaginal bleeding (other than postcoital) occurring between periods

Question 6

What are abnormal cells on histology of the cervix classed as?

Answer 6

Cervical intraepithelial neoplasia (CIN) - means that the disease is confined to the epithelium, it is a cancer when there is a breach of epithelial basement membrane

Question 7

What are risk factors for CIN?

Answer 7

• Cigarette smoking
• HIV
• Sex
  
  • Early age at first intercourse
  • Multiple sexual partners
  • High parity
  • STIs
• Prolonged oral contraceptive use > 5 years
• Weak immune system eg HIV, post transplant

Question 8

What is cervical intraepithelial neoplasia?

Answer 8

Disorganised proliferation of abnormal cells in squamous epithelium

• Lack of maturation
• Variation in cellular size and shape
• Nuclear enlargement
• Irregularity
• Hyperchromasia
• Cellular disarray

Question 9

What does CIN 1 indicate?

Answer 9

Mild dysplasia (basal 1/3rd of epithelium)

Question 10

What is the likelihood of CIN 1 progressing to cervical cancer?

Answer 10

Usually regress - 50-60% regress within 2 years

Question 11

What does CIN 2 indicate?

Answer 11

Moderate dyskaryosis

(basal 2/3rds of epithelium)

Question 12

What is the likelihood of CIN 2 progressing to cancer?

Answer 12

Regression is less likely - 3-5% develop cancer within 10 years

Question 13

What does CIN 3 indicate?

Answer 13

Severe dyskaryosis - full thickness changes

(>2/3rds epithelium)

Question 14

What is the likelihood of CIN 3 progressing to cancer?

Answer 14

Regression unlikely - 20-40% develop cancer in 10 years

Question 15

What screening programme is available to women to monitor for CIN and cervical cancer?

Answer 15

Cervical smear:

• Aged 25-49 - screened every 3 years
• Aged 50-64 - screened every 5 years

Uses liquid-based cytology to assess the cells of the cervix for premalignant or malignant change

Question 16

Peak age of cervical cancer

Answer 16

25-45 years

(80% of cases in developing world)

Question 17

If someone had normal cervical smear, how would you manage them?

Answer 17

Follow up in 3 years

Question 18

How would you follow up someone with an unsatisfactory cervical smear?

Answer 18

Repeat smear in 3 months

Question 19

How would you manage someone with suspected CIN1?

Answer 19

Conservative:

• High risk HPV testing
  
  • If +ve refer for colposcopy within 6 weeks
  • If -ve - repeat in 3 years

Question 20

How would you manage someone with CIN 2?

Answer 20

• Refer for colposcopy +/- LLETZ within 2 weeks
• 6 month follow up

Question 21

How would you manage someone with CIN 3?

Answer 21

• Refer for colposcopy +/- LLETZ within 2 weeks
• 6 month follow up

Question 22

What is involved in LLETZ (loop diathermy)?

Answer 22

https://www.youtube.com/watch?time_continue=26&v=rxs5Rg4hn9U

Cone of tissue is removed from cervix. Can be used to biopsy and treat CIN and early cervical cancer

Question 23

What is involved in colposcopy?

Answer 23

Cervix is inspected and acetic acid is applied to its surface – abnormal cells have increased surface proteins, which are coagulated by the acid and turn white, producing “acetowhite” areas which can be biopsied for histological assessment

Question 24

What are criteria for colposcopy referral?

Answer 24

• High grade dyskariosis
• 3 x unsatisfactory results
• Persisting low grade dyskariosis
• Clinically suspicious cervix

Question 25

What are the main treatment options for CIN?

Answer 25

* **LLETZ** * **Cold coagulation** * **Laser ablation**

Question 26

If someone was treated for CIN 2/3 with LLETZ and was HPV -ve at 6 months, how would you follow them up?

Answer 26

3 yearly follow up

Question 27

How often should HIV positive individuals have a cervical smear?

Answer 27

Every year

Question 28

What vaccinations are available for preventing HPV?

Answer 28

* **Cervarix (Bivalent)** - 16/18 * **Quadravalent (Gardasil)** - 16/18/6/11

Question 29

When are females given their HPV vaccine (based on vaccine schedule)?

Answer 29

12-13 years at 0, 1 and 6 months

Question 30

What are symptoms of cervical cancer?

Answer 30

May be completely asymptomatic (hence testing): * **Abnormal PV bleeding** * **Post coital bleeding** * **Intermenstrual bleeding** * **Menorrhagia** * **Postmenopausal bleeding** * **Discharge** * **Increased/altered vaginal discharge** * **Offensive** * **Symptoms of advanced disease** - pelvic pain, leg pain/swelling, GI problems, lung problems

Question 31

What are signs of cervical cancer?

Answer 31

Usually normal except in advanced disease: * **Pelvic mass** * **Craggy hepatomegaly** * **Speculum** - bleeding, discharge or obvious ulceration * **Bimanual** - friable tissue, obliteration of fornices, roughened, hard, irregular cervix which may be fixed/immobile "BOGGY UTERUS" May have leg oedema from lymphatic obstruction

Question 32

What are causes of post-coital bleeding?

Answer 32

* **Trauma** * **Ectropian** * **Cervicitis** * **Cervical/endometrial polyp** * **Cervical cancer** * **Vaginitis** * **Vaginal cancer** * **Vulval dermatitis** * **Vulval cancer** * **STIs** - Gonorrhoea, Chlamydia

Question 33

What are causes of intermenstrual bleeding?

Answer 33

* **Physiological** * **Trauma** * **Ovarian tumour** * **Uterus** - endometritis/PID, polyp, hyperplasia, fibroids, cancer * **Cervix** - cervicitis, polyp, cancer * **Vagina** - vaginitis, cancer * **Vulva** - dermatitis, dystrophy, cancer * **Pregnancy -** miscarriage, ectopic, molar pregnancy * **Systemic** - bleeding disorder, metastatic cancer * **Iatrogenic** - IUCD, HRT, POP, depoprovera * **STIs** - gonorrhoea, chlamydia * **Bleeding from somewhere else** - urethra, bladder, anus, rectum

Question 34

What investigations would you consider doing in an attempt to diagnose someone with suspected cervical cancer?

Answer 34

* **Bloods** - pregnancy test * **Imaging** - TVUSS + endometrial sampling * **Other -** Swabs for STI, **_colposcopy + punch biopsy_** Premanopausal women with abnormal bleeding should be tested for chlamydia Note that cervical smears detect pre-cancer, not cancer when asymptomatic

Question 35

What investigations would you do to stage cervical cancer?

Answer 35

* **Bloods** - FBC, U+E's, LFTs * **Imaging** - CXR, CT abdo/pelvis, MRI pelvis, PET scan, * **Other** - cystoscopy, protoscopy/sigmoidoscopy, surgical staging

Question 36

What does surgical staging of cervical cancer involve?

Answer 36

Examination under anaesthesia: * **LLETZ** * **Cystoscopy** * **Hyesteroscopy** * **Fractional currettage from endocervix and endometrium**

Question 37

What staging system is used to stage cervical cancer?

Answer 37

FIGO staging system

Question 38

What is stage 0 cervical cancer?

Answer 38

**CIN** - carcinoma in situ

Question 39

What is stage I cervical cancer?

Answer 39

Cancer limited to the cervix

Question 40

What is stage II cervical cancer?

Answer 40

Extension to uterus/parametria/vagina

Question 41

What is stage III cervical cancer?

Answer 41

Extension to pelvic side wall and/or lower third of the vagina

Question 42

What is stage IV cervical cancer?

Answer 42

Cancer tha has extended to adjacent organs or beyond true pelvis

Question 43

How would you manage stage 0 cervical cancer?

Answer 43

Colposcopy + LLETZ

Question 44

How would you manage stage Ia1 cervical cancer?

Answer 44

* **LLETZ or cone biopsy** - can be considered curative if excision margins are clear and preserve fertility * **Offer hysterectomy if family is complete**

Question 45

How would you manage stage Ia2 cervical cancer?

Answer 45

**Simple hysterectomy and Bilateral lymph node dissection (BPND)**

Question 46

How would you manage stage Ib1 cervical cancer?

Answer 46

Radical hysterectomy and BPND

Question 47

What is involved in simple hysterectomy?

Answer 47

Removal of uterus and cervix

Question 48

What is involved in a radical hysterectomy?

Answer 48

Removal of uterus, fallopian tubes, cervix, upper vagina and parametrium

Question 49

How would you manage someone with stage Ib2 and stage IIa cervical cancer?

Answer 49

Radical hysterectomy + BPND if no evidence of lymph node involvment

Question 50

How would you manage cervical cancer stage IIB and above?

Answer 50

These are inoperable (unless radical destructive surgery considered): * **Combination chemoradiotherapy**

Question 51

What types of radiotherapy are used to manage cervical cancer?

Answer 51

* **External beam irradiation** * **Intracavity brachytherapy**

Question 52

What chemotherapeutic agents are used in cervical cancer?

Answer 52

* **Cisplatin** * **Topotecan**

Question 53

What are complications of hysterectomy?

Answer 53

* **Bleeding** * **Infection** * **VTE** * **Ureteric fistula** * **Bladder dysfunction** * **Lymphoedema**

Question 54

What are complications of radiotherapy in cervical cancer?

Answer 54

* **Acute bladder/bowel dysfunction with tenesmus, mucositis, bleeding, ulceration, strictures and fistula** * **Vaginal stenosis, shortening and dryness**

Question 55

What is cervical ectropian?

Answer 55

Red ring around the os due to endocervical epithelium extending past its trritory over paler epithelium of the ectocervix

Question 56

What treatments are used if screening shows no cervical cancer but shows biological changes

Answer 56

* Large loop excision of the transformation zone (LLETZ) * Cone biopsy * Laser therapy

Question 57

What fertility sparing surgery can be done?

Answer 57

Trachelectomy - only in early stage disease (Ia2 and Ib) if LN proven to be neg following lymphadenopathy Vaginal procedure and involves removal of cervix and para-cervical tissue, to the elvel of internal os Permanent cerical suture inserted to prevent pre-term labour and will require delviery by C-section

Question 58

What can cause cervical ectropian?

Answer 58

Normal phenomenon * Puberty * The pill * Pregnancy Cervicitis

Question 59

Is cervical ectropian prone to bleeding?

Answer 59

Yes - columnar epithelium is much more fragile than squamous epithelium

Question 60

What is the following?

Answer 60

**Cervical polyp** - pedunculated benign tumours of endocervical epithelium which may cause increased mucus discharge or postcoital bleeding

Question 61

How would you manage someone with cervical polyps?

Answer 61

* **Pre-menopause** - Simple avulsion * **Peri/post menopause** - TVS +/- hysteroscopy

Question 62

What are causes of cervicitis?

Answer 62

* **Chlamydia** * **Gonorrhoea** * **Herpes** * **Can mask neoplasia**

Question 63

What is the following?

Answer 63

**Cervicitis** - may be follicular or mucopurulent, presenting with discharge

Question 64

What areas of the cervix does cervical screening aim to sample?

Answer 64

* **Squamous part** * **Transition zone** * **Columnar part**

Question 65

How is a cervical smear taken?

Answer 65

Brush inserted and rotated

Question 66

If a woman is nulliparous/has never had sex, what type of cervical cancer are they at risk of?

Answer 66

Adenocarcinoma of the cervix - due to lack of exposure to HPV

Question 67

What are the wilson criteria for developing a screening programme?

Answer 67

* **I**mportant – the condition should be an important one * **A**cceptable treatment for the disease * **T**reatment and diagnostic facilities should be available * **R**ecognisable at an early stage of symptoms * **O**pinions/policy on who to treat as patients must be agreed * **G**uaranteed safety e.g. low radiation exposure * **E**xamination must be acceptable by the patient * **N**atural history of the disease must be known * **I**nexpensive test * **C**ontinuous screening i.e. not a one-off

Question 68

How often are women screened?

Answer 68

Between 25-49 every 3 years Between 50-64 every 5 years

Question 69

Action taken if borderlink dyskanosis

Answer 69

Original sample tested for HPV. If neg patient does back to reoutine re-call. If pos they are referred for colposcopy.

Question 70

Action taken if moderate dyskariosis

Answer 70

Consistent with CIN 2. Refer for urgen colposcopy

Question 71

Action taken if severe dyskariosis or suspected invasive cancer

Answer 71

refer urgently

Question 72

Action taken in sample inadequate

Answer 72

Repeat - if 3 inadequate samples assessment by colposcopy

Question 73

What do cells with dyskariosis look like

Answer 73

Altered nuclear features - size, sahpe and outline, nucleoli

Question 74

Whats the difference between low or high grade dyskinesia?

Answer 74

Reflects decree of underlying CIN eg high grade=1.4%, low grade=0.8%

Question 75

Criteria for colposcopy referral

Answer 75

3 consequtive inadequate smear samples 3 borderline smears Mild/moderate/severe dyskaryosis (depends on size of nucleus) Suspected invasive disease

Question 76

What is the transzitional zone

Answer 76

Columnar epithelium lines the endocervix, squamous epithelium lines the exocervix. The junction betweent the 2 is the squamo-olumnar epithelium. At puberty and pregnancy the endocerviacl epithelium is pushed out and glandular lining cells are transferred into squamous cells. It is an unstable zone where many pre-cancerous lesions arise.