Cervical Cancer

Question 1

Comment on the epidemiology of cervical cancer

Answer 1

In Ireland 180 cases are diagnosed annually, and 80 will die from it

3rd most common cancer worldwide

Unlike many other cancers it is a cancer of the young with a peak age of diagnosis between 25-29. half of all cases are diagnosed before 47. Peak again in their 80s

Question 2

What is the aetiology and pathophysiology of cervical cancer?

Answer 2

80% squamous cell carcinoma, 20% adenocarcinoma

Cervical cancer usually develops as a progression from cervical intraepithelial neoplasia (CIN). This occurs over the course of 10-20 years, although not all cases of CIN progress to cancer (and most spontaneously regress).

Invasive cervical cancer occurs when the basement membrane of the epithelium has been breached. The most common sites of metastasis are the lung, liver, bone and bowel.

The vast majority of cervical squamous cell cancers are caused by persistent human papillomavirus (HPV) infection. Indeed, 99.7% of cases contain HPV DNA within the cancerous cells.

Question 3

What is HPV?

Answer 3

The human papilloma virus is a sexually transmitted virus which affects the skin and mucous membranes. There are more than 100 different strains, of which around 30 affect the genital area.

HPV is highly prevalent, with around 80% of women thought to be infected at some point. However, the majority of infections are cleared by the immune system within 2 years. Some cases persist, and these can go on to cause malignant changes such as CIN and cervical cancer over a course of many years.

Not all HPV types are oncogenic. HPV 6 and 11 are low-risk serotypes that cause genital warts and are unlikely to cause cancer. The most common high risk serotypes are 16 and 18. They are thought to produce proteins which inhibit the tumour suppressor protein p53 in cervical epithelial cells, allowing for uncontrolled cell division.

In the UK, the National HPV vaccination programme provides protection against HPV 16 and 18 (the cause of 70% of cervical cancer cases), as well as HPV 6 and 11. The combination of screening and vaccinations are thought to account for a 40% reduction in incidence in the UK, and prevent roughly 2000 deaths per year.

Question 4

Risk factors for cervical cancer?

Answer 4

As discussed above, infection with human papilloma virus is the greatest risk factor for cervical cancer. Other risk factors include:

Smoking
Other sexually transmitted infections
Long-term (> 8 years) combined oral contraceptive pill use
Immunodeficiency (e.g. HIV)

Question 5

What are the clinical features of cervical cancer?

Answer 5

The most common presenting symptom of cervical cancer is abnormal vaginal bleeding (e.g post-coital, intermenstrual or post-menopausal). Other clinical features include vaginal discharge (blood-stained, foul-smelling), dyspareunia, pelvic pain and weight loss.

However, it is often asymptomatic – particularly in the early stages of disease – and many cases are detected through routine screening.

In advanced disease, the patient may experience oedema, loin pain, rectal bleeding, radiculopathy and haematuria. These often occur as a result of the cancer invading into nearby structures.

Question 6

What clinical examinations may be helpful in investigating cervical cancer?

Answer 6

A thorough clinical examination is required in cases of suspected cervical cancer and includes:

Speculum examination – assess for evidence of bleeding, discharge and ulceration.
Bimanual examination – assess for pelvic masses.
GI examination – assess for hydronephrosis, hepatomegaly, rectal bleeding, mass on PR.

Question 7

What would be your differential diagnosis of cervical cancer?

Answer 7

There are a large number of possible causes for abnormal vaginal bleeding. These include sexually transmitted infection, cervical ectropion, polyp, fibroids, and pregnancy related bleeding.

In the post-menopausal population, always exclude endometrial carcinoma.

Question 8

Whats cervical check?

Answer 8

Irish National Cervical Screening Program (CervicalCheck)

1. Aged 25-65
   * 25-29 every 3 years
   * 30-65 every 5 years
2. Screen for high-risk types of HPV
3. If found, same sample checked for abnormal cells

Question 9

HPV screening - what to do if none found?

Answer 9

routine recall
Aged 25-65
* 25-29 every 3 years
* 30-65 every 5 years

Question 10

HPV screening - if HPV found and there is no abnormal cells/changes?

Answer 10

repeat in 12 months

Question 11

If HPV is found and there are abnormal cell changes found?

Answer 11

Refer to colposcopy

Question 12

HPV screening - if there is an inadequate sample?

Answer 12

repeat within 3 months

Question 13

Cytology screening - borderline nuclear changes?

Answer 13

usually associated with HPV infection or atrophic vaginitis

Question 14

Cytology screening - low grade

Answer 14

mild/moderate dyskaryosis

Question 15

Cytology screening high grade

Answer 15

moderate/severe dyskaryosis

Severe dyskaryosis – abnormal cytoplasmic maturation and high nuclear : cytoplasmic ratio ; colposcopy referral

Question 16

Cytology screening - atypical?

Answer 16

Atypical cytology – Atypical Squamous Cells of Undetermined Significance (ASCUS), Atypical Squamous Cells of Undetermined Significance but High-grade changes cannot be ruled out (ASCH)

typical Glandular cells – possibility of
cervical adenocarcinoma

Question 17

CIN Histological diagnosis - what do each mean?

Answer 17

Where the dysplasia is found. grows upwards from the basal layer.

CIN 1 - lower 1/3 of the epithelium
CIN 2 - lower 2/3 of the epithelium
CIN 3 - whole thickness of the epithelium

Question 18

What does CIN stand for?

Answer 18

Cervical intraepithelial neoplasia

Question 19

If a premenopausal woman presents with symptoms of cervical cancer what do you do?

Answer 19

1. rule out other things e.g. chlamydia. if chlamydia positive treat and retest. If doesn’t respond to treatment then colposcopy and biopsy.

Question 20

What if a postmenopausal woman presents with symptoms of cervical cancer?

Answer 20

urgent colposcopy and biopsy.

Question 21

What is a colposcopy?

Answer 21

A colposcopy is where a colposcope is inserted through the vagina to view the cervix. Acetic acid is used to stain dysplastic areas white and a biopsy is taken.

• Outpatient
• Cervix examined via biocular microscope
• Lithotomy positions and cuscos speculum
• Acetic acid applied on cervix

Question 22

Indications for colposcopy?

Answer 22

Indications – HPV detected and cytology determines need for colposcopy

• ASCUS
• Second negative cytology after 2 +ve HPV
• HPV positive and detected
• Discharged from colposcopic surveillance with increased HPV
  screening
• 3rd intermediate screening result

Question 23

What are the features of cervical cancer on colposcopy?

Answer 23

Features on colposcopy –
degree of acetowhite staining on cervix,
punctuations (vascular prominence),
mosaicism (branching of tree pattern),
abnormal vessels;
Schiller’s Test (Lugol’s Iodine stains glycogen brown – abnormal cells have less glycogen so stain less

Question 24

How is cervical cancer staged?

Answer 24

Stage 0 = carcinoma in situ
Stage 1 = confined to cervix
1a = microscopically
1b = can be seen clinically

Stage 2= extends beyond the cervix. Does not get the pelvic side wall or the lower 1/3 of the vagina.
2a = no parametrial involvement
2b = parametrial involvement

Stage 3 = extends beyond cervix, includes pelvic side wall and lower 1/3 of vagina and hydronephrosis

Stage 4 = extends to bladder or rectum or metastases
4a = involves bladder/ rectum
4b = involves distant organs

Question 25

Management of cervical cancer?

Answer 25

In the management of cervical cancer, it is important to consider the stage of disease, co-morbidities and fertility issues when deciding on treatment.

As with all cancers, treatment involves multidisciplinary input. Possible options include surgery, radiotherapy, and chemotherapy.

Surgical Options
The available surgical options are dependant on the stage of the cancer:

Stage 1a

Radical trachelectomy if fertility-preservation is a priority. This involves removal of the cervix and upper vagina. Otherwise, a laparoscopic hysterectomy with pelvic lymphadenectomy is offered.

Stage 1b/2a

Radical (Wertheim’s) hysterectomy as a curative treatment modality. Involves removal of the uterus, vagina and parametrial tissues up to the pelvic sidewall, plus lymphadenectomy.

Stage 4a or Recurrent disease

Anterior/posterior/total pelvic extenteration. Removal of all pelvic adnexae plus bladder (anterior)/rectum (posterior or both (total).

Radiotherapy
Radiotherapy is often a combination of external beam therapy and intracavity brachytherapy. If offers an acceptable alternative to surgery in early-stage disease.

Stage 1b to 3

Offered in conjunction with chemotherapy over a 5-8 week course. Evidence suggests additional hysterectomy offers no benefits in terms of survival for these stages. Therefore chemoradiation therapy is the gold standard.

Chemotherapy
Chemotherapy in cervical cancer is often cisplatin-based.

It can be given before treatment by surgery or radiotherapy (known as neoadjuvant chemotherapy), or after treatment (adjuvant chemotherapy).

It is also the mainstay of treatment in the palliative setting.

Question 26

Cervical cancer post treatment follow up?

Answer 26

Patients should be reviewed by a gynaecologist every 4 months after treatment has been completed for the first 2 years, and every 6-12 months for the subsequent 3 years.

All follow-ups should involve a physical examination of the vagina and cervix (if they haven’t been removed).

Note – Cervical smear testing is no longer valid after radiotherapy.

Question 27

Management options if small in colposcopy etc I think

Answer 27

large loop excision of the transformational zone

radical electro diathermy, cryotherapy, laser vaoprisation, cold coagulation, cone biopsy
cytology follow up in 6 months
prevention HIV vaccine