4. Cervix

Question 1

Epidemiology of cervical cancer

Answer 1

Peak incidence: 35–44 years of age

Question 2

Etiology for cervical cancer

Answer 2

Human papillomavirus virus (HPV) infection

1. Infection with high-risk HPV types is the main cause of cervical cancer (DNA of HPV 16 and/or 18 is found in 70% of all patients with cervical carcinoma)
2. The major high-risk HPV types are HPV 16 (most common in squamous cell carcinoma) and HPV 18 (most common in adenocarcinoma)

Question 3

Risk factors for cervical cancer

Answer 3

1. Associated with HPV infection
   - Multiple sexual partners (strongest risk factor)
   - Early-onset of sexual activity
   - Multiparity
   - Immunosuppression (e.g., HIV infection, post-transplantation)
   - History of sexually transmitted infections (e.g., herpes simplex, chlamydia)
2. Environmental risk factors
   - Cigarette smoking and/or exposure to second-hand smoke (for squamous cell cancer types only)
   - In-utero exposure to diethylstilbestrol (DES)

Question 4

Clinical features of cervical cancer

Answer 4

Usually asymptomatic in the early stages

Early symptoms:

1. Abnormal vaginal bleeding: irregular vaginal bleeding, heavy, irregular menstrual bleeding, postcoital spotting
2. Abnormal vaginal discharge: blood-stained or purulent malodorous discharge (not necessarily accompanied by pruritus)
3. Dyspareunia
4. Pelvic pain

Late symptoms:

1. Hydronephrosis
2. Lymphedema
3. Fistula formation

Question 5

Cervical cancer screening

Answer 5

Pap smear

Question 6

Definition of cervical intraepithelial neoplasia

Answer 6

1. Precursor lesion characterized by epithelial dysplasia that begins at the basal layer of the squamocolumnar junction and extends outward
2. May progress to invasive carcinoma if left untreated

Question 7

Classification of cervical intraepithelial neoplasia

Answer 7

CIN I: mild dysplasia, involves ∼ ⅓ of the basal epithelium

• Koilocytes may be present
  i. Epithelial cells with perinuclear halos
  ii. Pathognomonic for HPV infection

2. CIN II: moderate dysplasia, involves ⅓–⅔ of basal epithelium
3. CIN III: severe, irreversible dysplasia or carcinoma in situ, involves > ⅔ of basal epithelium

Question 8

Definition of invasive cervical cancer

Answer 8

1. Characterised by invasion beyond the basement membrane of the cervical epithelium
2. Cervical carcinoma most commonly arises from metaplastic squamous cell epithelium in the transformation zone

Question 9

Classification of invasive cervical cancer

Answer 9

Squamous cell carcinoma: ∼ 80% of cases

1. Subtypes include large cell keratinizing, large cell nonkeratinizing, and papillary squamous cell carcinoma.
2. Irregular cell morphology
3. Hyperchromatic cells with nonspherical nuclei, mitotic activity, and prominent nucleoli
4. Loss of basal membrane

Adenocarcinoma: ∼ 20% of cases

1. Subtypes include mucinous, endometrioid, clear-cell, and serous adenocarcinoma
2. The most common is the endocervical mucinous subtype
3. Atypical columnar epithelium with elongated nuclei

Small-cell carcinoma: ∼ 2% of cases

Question 10

Modes of spread of invasive cervical cancer

Answer 10

1. Direct local invasion
   - Uterus, vagina
   - Bladder, rectum (fistulas)
2. Lymphatics
3. Hematogenous
   - Lung, liver, bone, brain