The Cervix and Its Abnormalities

Question 1

Define cervical ectropion

Answer 1

Columnar epithelium of endocervix is visible as read area around the os on surface of cervix

Question 2

What causes cervical ectropions?

Answer 2

 Due to eversion
 Normal in younger women, especially pregnant and those taking COCP

Question 3

How do cervical ectropions present?

Answer 3

 Normally asymptomatic
 Can cause discharge or PCB

Question 4

How do we manage cervical ectropions?

Answer 4

 Tx with cryotherapy
 Need to perform smear and ideally colposcopy to exclude Ca before

Treatment involves cauterisation of the ectropion using silver nitrate or cold coagulation during colposcopy.

Question 5

What are women with cervical ectropions at risk of?

Answer 5

 Exposed columnar epithelium = more prone to infection

Question 6

How common is acute cervicitis? How is at risk of getting them?

Answer 6

Rare, often results from STDs.

Question 7

What causes chronic cervicitis? How does it present? How is it managed?

Answer 7

Can get chronic cervicitis → due to inflammation or infection (often of ectropion)
o Common cause of vaginal discharge
o Can get ‘inflammatory’ smear

 Tx with cryotherapy + abx (depending on bacterial culture)

Question 8

Define cervical polyps.

Answer 8

Benign tumours of endocervical epithelium

Question 9

Who gets cervical polyps? How big are they?

Answer 9

Common in women >40 years and usually <1cm

Question 10

How do cervical polyps present?

Answer 10

Asymptomatic or PMB/PCB

Question 11

How do we manage cervical polyps?

Answer 11

Small polyps: avulsed w/o local, examine histologically, bleeding abnormalities my still be investigated

Question 12

What are Nabothian follicles? How big do they tend to be? What happens?

Answer 12

• Nabothian cysts are fluid-filled cysts often seen on the surface of the cervix.
• They are also called nabothian follicles or mucinous retention cysts.
• They are usually up to 1 cm in size, but rarely can be more extensive.
• They are harmless and unrelated to cervical cancer.

The columnar epithelium of the endocervix (the canal) produces cervical mucus.

When the squamous epithelium of the ectocervix slightly covers the mucus-secreting columnar epithelium, the mucus becomes trapped and forms a cyst.

This can happen after childbirth, minor trauma to the cervix or cervicitis secondary to infection.

Question 13

How do Nabothian cysts present?

Answer 13

Nabothian cysts are often found incidentally on a speculum examination. They do not typically cause any symptoms. Rarely, when they are very large, they may cause a feeling of fullness in the pelvis.

Nabothian cysts appear as smooth rounded bumps on the cervix, usually near to os (opening). They can range in size from 2mm to 30mm, and have a whitish or yellow appearance.

Question 14

How do we manage Nabothian cysts?

Answer 14

Where the diagnosis is clear, women can be reassured, and no treatment is required. They do not cause any harm and often resolve spontaneously.

If the diagnosis is uncertain, women can be referred for colposcopy to examine in detail. Occasionally they may be excised or biopsied to exclude other pathology. Rarely they may be treated during colposcopy to relieve symptoms.

Question 15

Define cervical intraepithelial neoplasia.

Answer 15

 Presence of atypical cells within the squamous epithelium

Question 16

What is different about CIN cells?

Answer 16

• Dyskaryotic
• Exhibit large nuclei
• Frequent mitoses

Question 17

How do we grade CINs? When does malignancy ensue?

Answer 17

Severity graded I-III - and is dependent on the extent to which these cells are found in the epithelium (therefore a histological diagnosis)

CIN I: Mild dysplasia, atypical cells only in lower 1/3 epithelium

CIN II: Moderate dysplasia, atypical cells in lower 2/3 epithelium

CIN III: Severe dysplasia: atypical cells occupy full thickness of epithelium = carcinoma in situ

Malignancy ensues when these abnormal cells invade through the BM.

Question 18

What is the prognosis of CINs?

Answer 18

If untreated, about ⅓ of women with CIN II/III will develop cervical cancer over the next 10 yrs.

CIN I has the least malignant potential, commonly regress spontaneously.

Question 19

Describe the epidemiology of CIN.

Answer 19

Cervical intra-epithelial neoplasia - more common

90% cases of CIN III are women under 45 years, peak incidence at 25-29 years

Question 20

Describe the aetiology of CIN.

Answer 20

• HPV
• Most important factor = number of sexual contacts, particularly at an early age
• 16, 18, 31, 33 are frequently associated with CxCa
• Vaccination against individual viruses reduces incidence of precancerous cervical lesions and potentially CxCa
• Vaccine should be given before first sexual contact → does not help established CIN
• Current UK vaccine targets 16 and 18 = 75% of CxCa in the UK
• Other risk factors: OCP, smoking, immunocomprimised patients

Human papillomavirus (HPV), particularly serotypes 16,18 & 33 is by far the most important factor in the development of cervical cancer. Other risk factors include:

• smoking
• human immunodeficiency virus
• early first intercourse, many sexual partners
• high parity
• lower socioeconomic status
• combined oral contraceptive pill*

Question 21

Describe the pathology of CIN.

Answer 21

 As columnar epithelium undergoes metaplasia to squamous epithelium, exposure to HPV → incorporation of viral DNA into cellular DNA
 Viral proteins activate TSG products → push cell into cell cycle
 Overtime other accumulation of mutations → carcinoma
 Viruses hide infected cell from immune system

Question 22

How do we diagnose cervical cancer?

Answer 22

CIN causes no symptoms and is not visible on cervix
Screening identifies women at high risk of developing CxCa who could be treated before the disease develops. - VITAL

Question 23

When should screening for cervical cancer start and end? How often should it be done?

Answer 23

From age 25 yrs or after first intercourse if later, and then repeated every 3 yrs until the age of 49 yrs.

Between 50 yrs and 64 yrs, smears performed every 5 yrs.

From age 65, only those who have not been screened since age 50 or have had recent abnormal tests are screened

Abnormal smear identifies those at risk of CIN and therefore risk of CxCa

Women under 25 years often have abnormal cervical changes but risk of CxCa is low - therefore commencing age 25 reduces number of unnecessary recalls and colposcopies

Women diagnosed with CxCa has halved since introduction of screening programme in 1988 and prevents 5000 deaths per year

Question 24

How are smear results interpreted?

Answer 24

 Smears identify cellular abnormalities as only superficial cells are sampled

 Cellular abnormalities = dyskaryosis, graded borderline, low or high grade.

 Dyskaryosis is suggestive of CIN and the grade partly reflects the severity of CI.Nc

• Inadequate — this may be because the cervical sample:
  
  • Was taken but the cervix was not fully visualized.
  • Was taken in an inappropriate manner (for example, using an unapproved device).
  • Contains insufficient cells.
  • Contains an obscuring element (for example lubricant, inflammation, or blood).
  • Is incorrectly labelled.
• Negative — no abnormality is detected.
• Abnormal — the cervical samples may show:
  
  • Borderline changes in squamous or endocervical cells.
  • Low-grade dyskaryosis.
  • High-grade dyskaryosis (moderate).
  • High-grade dyskaryosis (severe).
  • Invasive squamous cell carcinoma.
  • Glandular neoplasia.

Question 25

**What should happen following a normal cervical cytology result?**

Answer 25

* Individuals who are positive for high-risk human papillomavirus (hrHPV) and receive a negative cytology report as part of routine primary HPV screening should have the HPV test repeated at 12 months. * If HPV testing is negative at 12 months, individuals can be safely returned to routine recall. * Individuals who remain hrHPV positive, cytology negative at 12 months should have a repeat HPV test in a further 12 months. * Individuals who become hrHPV negative at 24 months can be safely returned to routine recall. * Individuals who remain hrHPV positive, cytology negative or inadequate at 24 months should be referred to colposcopy. * Individuals who remain hrHPV positive with cytology reported as borderline dyskaryosis or worse at 12 or 24 months should be referred to colposcopy.

Question 26

**What should happen following an abnormal cervical cytology result?**

Answer 26

* **All individuals who are positive for high-risk human papillomavirus (hrHPV) and have abnormal cytology are referred to colposcopy.** * **Ensure the person has received an explanation about what an abnormal result means and what further tests or treatment may be needed.**

Question 27

Describe the colposcopy procedure.

Answer 27

* **At colposcopy the cervix is assessed in detail using a colposcope.** * **The colposcopist:** * Looks for any abnormal changes in the cervix which may indicate pre-cancerous changes (cervical intraepithelial neoplasia [CIN]) or the presence of cancer. * Usually applies chemicals to the cervix, for example: * If acetic acid is applied to the cervix, abnormal areas (such as CIN) tend to turn white (sometimes referred to as acetowhite). * If an iodine solution is applied, normal tissue (on the outside of the cervix) stains dark brown. Pre-cancerous abnormalities may not stain with iodine. The cells on the inner part of the cervix do not stain brown. * May take a biopsy to confirm the diagnosis.

Question 28

**What should happen if results are unavailable or if there is an inadequate cervical cytology sample?**

Answer 28

* If the high-risk human papillomavirus (hrHPV) test result is unavailable or cytology is inadequate at any screening episode in the pathway — the sample is repeated in no less than 3 months. * Individuals who have inadequate cytology at the 24 month repeat test are an exception — these people are referred to colposcopy. * Individuals who have two consecutive HPV results unavailable or inadequate cytology results, in any combination are referred to colposcopy. * Individuals who have a normal and adequate colposcopy examination should be followed up in the community at 12 months. * If hrHPV testing is negative at 12 months, the individual is returned to routine recall. * If colposcopy is inadequate, individuals should have a repeat screening test and colposcopy examination in 12 months. * If the repeat colposcopy is normal and HPV negative, the individual is discharged to routine recall.

Question 29

How are CINs treated? What is the risk associated with it?

Answer 29

Prevent invasive CxCa If there are moderate to severe abnormalities can excise or ablate the region. Excision – LLETZ (large loop excision of the transformation zone). Involves removal of abnormal cells using a thin wire loop that is heated by electric current. - this specimen is diagnosed histologically. Risk = Large excision or repeat excisions are associated with an **increased risk of midtrimester miscarriage** and **preterm delivery.** Cone biopsy can also be done (less common). Requires a test of cure 6mo later

Question 30

How would you counsel a patient after screening and results of CIN?

Answer 30

Question 31

Describe the epidemiology of malignant disease of the cervix.

Answer 31

Cervical cancer accounts for 8% of cancers diagnosed in women worldwide It has been estimated that the lifetime risk in the UK of developing cervical cancer is 1 in 135  Two peaks of incidence: 30s and 80s  Majority 25-49 years

Question 32

Describe the pathology of cervical cancer.

Answer 32

 90% are squamous cell carcinomas  10% adenocarcinoma – worse prognosis and increasing in proportion as smear programme prevents more squamous cell carcinomas

Question 33

Describe the aetiology of cervical cancer.

Answer 33

 Same causative factors as CIN  HPV is found in all cervical cancers  Immunosuppression accelerates process of invasion from CIN  Not familial

Question 34

What are the clinical features of cervical cancer?

Answer 34

Many women with cervical cancer will be asymptomatic * Consider the possibility of cervical cancer in a woman who has any of the following nonspecific symptoms: * Intermenstrual bleeding. * Postcoital bleeding (risk of cervical cancer increases with age). * Postmenopausal bleeding. * Blood-stained vaginal discharge. * Mucoid, or purulent vaginal discharge. * Pelvic pain/dyspareunia. * Rarely, women may present with advanced cancer with such symptoms as pelvic discomfort or pain, renal failure, leakage of urine or faeces from a fistula, lymphoedema, or severe haemorrhage. * On examination: * The cervix may appear inflamed or friable and bleed on contact (although the most likely cause for this will be *Chlamydia trachomatis.* * There may be a visible ulcerating or fungating lesion or a foul-smelling serosanguineous vaginal discharge.

Question 35

How do we evaluate stage and spread of cervical cancers?

Answer 35

 Tumour spreads locally to parametrium and vagina, then to pelvic side wall  LN spread → pelvic nodes = early feature  FIGO classification is clinical * **Stage I:** The carcinoma is strictly confined to the cervix (extension to the uterus should be disregarded). * **Stage IA:** Diagnosed only by microscopy. * Stage IA1: Measured stromal invasion of not more than 3 mm in depth, and extension of not more than 7 mm. * Stage IA2: Measured stromal invasion of between 3 mm and 5 mm in depth, and extension of not more than 7 mm. * **Stage IB:** Clinically visible lesions confined to the cervix, or preclinical cancers greater than stage 1A. * Stage IB1: Lesions not more than 4 cm in size. * Stage IB2: Lesions more than 4 cm in size. * **Stage II:** The carcinoma extends beyond the uterus, but has not extended onto the pelvic wall or to the lower third of vagina. * Stage IIA: Involvement of up to the upper 2/3 of the vagina. No obvious parametrial involvement. * Stage IIA1: Lesions not more than 4 cm in size. * Stage IIA2: Lesions more than 4 cm in size. * Stage IIB: Obvious parametrial involvement but not onto the pelvic sidewall. * **Stage III:** The carcinoma has extended onto the pelvic sidewall. On rectal examination, there is no cancer free space between the tumour and pelvic sidewall. The tumour involves the lower third of the vagina. All cases of hydronephrosis or non-functioning kidney should be included unless they are known to be due to other causes. * Stage IIIA: Involvement of the vagina but no extension onto the pelvic side wall. * Stage IIIB: Extension onto the pelvic sidewall, or hydronephrosis/non-functioning kidney. * **Stage IV:** The carcinoma has extended beyond the true pelvis, or has clinically involved the mucosa of the bladder and/or rectum. * Stage IVA: Spread to adjacent pelvic organs. * Stage IVB: Spread to distant organs.

Question 36

How do we investigate cervical cancer?

Answer 36

Confirm diagnosis: tumour biopsy Stage disease: vaginal and rectal examination o Assess size of lesion and parametrial/rectal invasion o Examination under anaesthetic usualy performed o Cystoscopy for bladder involvement o MRI to detect tumour size, spread and LN involvement Assess fitness for surgery: CXR, FBC, U&Es

Question 37

How do we manage cervical cancer?

Answer 37

**Pregnant –** MDT approach + delivery post 35wks **Recurrent disease –** surgery / palliative chemo / supportive care

Question 38

Describe the prognosis of cervical cancers.

Answer 38

The death rate from cervical cancer dropped significantly in the last 40 years. Prognosis is related to the woman's: * **Age at diagnosis.** * **Stage** * **Disease recurrence** * **adenocarcinoma**