Cervical Carcinoma - Complete Examination Answer

Q21. Clinical Case: 47-year-old woman, post-coital bleeding, ulcerative cervical lesion 4×3 cm, bleeds on touch

(a) Most Probable Diagnosis and One Differential (1 mark)

• Other differentials include cervicitis (especially due to Trichomonas), or a large nabothian cyst with secondary ulceration - however the most clinically significant differential is a cervical polyp or chronic cervicitis, as these can also present with a friable, bleeding lesion. Always confirm with biopsy.

(b) Risk Factors for Carcinoma of Cervix (2 marks)

Primary / Most Important

• HPV infection (high-risk types 16 and 18 account for ~70% of cases; also types 31, 33, 45)
• Multiple sexual partners (or partner with multiple partners)
• Early age at first intercourse (before age 17) - squamous metaplasia most active at the transformation zone in adolescence, making the cervix vulnerable

Other Risk Factors

• Cigarette smoking - increases risk 2-4 fold; acts as a co-carcinogen
• Immunosuppression (HIV infection, especially low CD4 count; organ transplant recipients)
• High parity / multiparity
• Low socioeconomic status and poor access to screening
• Long-term oral contraceptive use (>5 years)
• History of other STIs (HSV-2, Chlamydia)
• Non-use of barrier contraception
• In utero exposure to DES (diethylstilbestrol)
• Previous high-grade CIN (CIN 2/3)

Robbins & Kumar Basic Pathology: "Risk factors for cervical carcinoma are related to HPV exposure, such as early age at first intercourse, multiple sexual partners, and other factors including cigarette smoking and immunodeficiency."

(c) Management of Stage I Carcinoma of Cervix (5 marks)

FIGO Stage I Definition

Management Principles

1. Stage IA1 (Microinvasive - No LVSI)

• Cone biopsy (large loop excision - LEEP) with clear margins - sufficient for fertility preservation
• Simple (extrafascial) hysterectomy - if fertility not desired
• No lymph node dissection required if invasion ≤3 mm and no lymphovascular space invasion (LVSI)

2. Stage IA1 (with LVSI) and Stage IA2

• Modified radical hysterectomy (Type II Wertheim's hysterectomy) + pelvic lymph node dissection
• For fertility preservation: large cone biopsy + pelvic lymph node dissection (controversial but used in selected patients)

3. Stage IB1 (lesions ≤4 cm - like this patient's 4×3 cm lesion)

• Radical hysterectomy (Wertheim's/Type III) + bilateral pelvic lymph node dissection
  • Advantages: preserves ovarian function, avoids radiation sequelae, single operative treatment, allows pathological assessment
  • Procedure: en-bloc removal of uterus, upper vagina (2 cm), bilateral parametria, pelvic nodes
• Radical Radiotherapy (External Beam Radiation Therapy - EBRT + Brachytherapy)
  • EBRT: 45-50 Gy to pelvis over 4-5 weeks
  • Followed by intracavitary brachytherapy (boosts dose to cervix)
  • Combined with cisplatin-based chemosensitization (concurrent chemoradiation)

4. Stage IB2 (>4 cm - bulky tumors)

• Concurrent chemoradiation is preferred (cisplatin + radiation)
• Radical hysterectomy is less favored due to high likelihood of needing postoperative radiotherapy (which increases morbidity when combined with surgery)
• Neo-adjuvant chemotherapy followed by radical hysterectomy is under investigation

5. Fertility-Sparing for Stage IB1 (selected young women)

• Radical trachelectomy (removal of cervix with upper vagina and parametria, preserving the uterine corpus) + laparoscopic pelvic lymph node dissection
• Suitable for lesions <2 cm, no lymph node involvement
• Subsequent pregnancies are possible but higher-risk

Adjuvant Therapy (Post-Surgery)

• Positive lymph nodes
• Positive surgical margins
• Positive parametria
• Deep stromal invasion + LVSI + large tumor (Sedlis criteria)

Harrison's 22e: "Very small stage I cervical tumors can be treated with a variety of surgical procedures... Patients with large stage I cervical tumors (4 cm) confined to the cervix... are treated with radiation therapy in combination with cisplatin-based immunochemotherapy."

(d) Complications of Carcinoma of Cervix (2 marks)

Complications of the Disease Itself

1. Hemorrhage - from the tumor; can be life-threatening
2. Hydronephrosis / Renal failure - ureteric compression or invasion (especially in advanced disease)
3. Vesico-vaginal fistula (VVF) and recto-vaginal fistula (RVF) - from tumor invasion of bladder/rectum
4. Lymphedema of lower limbs - from pelvic lymph node involvement
5. Deep vein thrombosis - from iliac vessel compression
6. Sepsis - from infected, necrotic tumor
7. Distant metastases - to lungs, liver, bone

Complications of Treatment

• Ureterovaginal fistula, vesicovaginal fistula
• Bladder dysfunction (neurogenic bladder)
• Lymphedema of legs
• Ovarian failure (if bilateral oophorectomy done in premenopausal women)
• Sexual dysfunction

• Radiation proctitis / bowel fistula (1.4-5.3% rate)
• Radiation cystitis / hemorrhagic cystitis
• Vaginal fibrosis and stenosis
• Bowel obstruction, rectal stricture
• Secondary malignancies (rare)

Berek & Novak's Gynecology: "The bowel and bladder fistula rate after pelvic radiation therapy for cervical cancer is 1.4% to 5.3%, respectively."

* Methods of Cervical Cancer Screening, Diagnosis, and Management (KMCRI - 10 marks)

A. Screening Methods

1. Pap Smear (Papanicolaou Smear)

• Patient in lithotomy position
• Speculum inserted; cervix visualized
• Ectocervix sampled with an Ayre's spatula (wooden or plastic), rotating 360° around the os
• Endocervix sampled with a cytobrush (endocervical brush)
• Cells spread on a glass slide immediately and fixed with 95% ethyl alcohol (conventional) OR cells rinsed into a liquid preservative vial (ThinPrep/SurePath - liquid-based cytology)
• Stained with Papanicolaou stain; read by cytopathologist

• Negative for intraepithelial lesion or malignancy
• Epithelial cell abnormalities:
  • ASC-US (atypical squamous cells of undetermined significance)
  • ASC-H (cannot exclude HSIL)
  • LSIL (low-grade SIL) = HPV changes / CIN 1
  • HSIL (high-grade SIL) = CIN 2, CIN 3, CIS
  • Squamous cell carcinoma
  • Glandular cell abnormalities (AGC, AIS, adenocarcinoma)

• Sensitivity for HSIL: ~56%; Specificity for HSIL: ~97%
• Liquid-based cytology has the same sensitivity/specificity as conventional Pap but allows HPV co-testing from same sample

• Start at age 21 regardless of sexual debut
• Age 21-29: Pap smear every 3 years (cytology alone)
• Age 30-65: Pap smear every 3 years (cytology alone) OR every 5 years with HPV co-testing ("co-testing")
• Age >65 with adequate prior screening: stop screening
• After total hysterectomy (no history of CIN 2+): stop screening

2. HPV DNA Testing

• Cervical specimen placed in liquid transport medium
• RNA probes detect oncogenic HPV DNA-RNA hybrids (Hybrid Capture method) or PCR-based genotyping
• Detects high-risk HPV types (16, 18, 31, 33, 45, etc.)
• More sensitive but less specific than Pap smear for CIN 2/3
• Higher false-positive rates in women under 35
• Used as co-test with Pap (ages 30-65) or as primary screening (with reflex cytology if HPV+)
• HPV 16/18 genotyping: if positive, proceed directly to colposcopy

3. Visual Inspection with Acetic Acid (VIA)

• Low-cost, point-of-care test for low-resource settings
• 3-5% acetic acid applied to cervix; acetowhite areas indicate abnormal epithelium (dysplasia/cancer)
• Read immediately; no laboratory required
• Sensitivity ~80%, Specificity ~92% (variable)
• Used in WHO "Screen-and-Treat" strategy in developing countries

4. Visual Inspection with Lugol's Iodine (VILI)

• Lugol's iodine applied to cervix
• Normal glycogen-rich squamous cells stain mahogany brown
• Abnormal areas (lacking glycogen) appear mustard yellow (iodine non-uptake)
• Similar accuracy to VIA; used in resource-limited settings

5. Colposcopy

• Magnified (6-40x) visualization of cervix after application of acetic acid and iodine
• Used for triage of abnormal Pap smears or positive HPV tests
• Allows targeted biopsy of suspicious areas (acetowhite lesions, mosaic pattern, punctation, atypical vessels)
• Not a screening tool - a diagnostic/triage tool

B. Diagnosis of Cervical Cancer

1. History and Symptoms: Post-coital bleeding, intermenstrual bleeding, foul-smelling discharge, pelvic pain (advanced disease), urinary/rectal symptoms (very advanced)
2. Speculum Examination: Direct visualization of cervical lesion
3. Cervical Biopsy (Definitive): Punch biopsy from suspicious areas; histopathology confirms invasion
4. LEEP/Cone Biopsy: For microinvasive disease (IA) to assess depth and margins
5. EUA (Examination Under Anesthesia): For clinical staging - assesses extent of disease
6. Imaging for Staging/Treatment Planning:
   • MRI pelvis: best for local extent, parametrial involvement
   • CT chest/abdomen/pelvis: lymph node assessment, distant metastases
   • PET-CT: lymph node and distant disease (if available)
   • IVU/Cystoscopy/Proctoscopy: for FIGO clinical staging in advanced disease

C. Management (Summary by Stage)

* Indications and Technique of Pap Smear (NAMO - 2 marks)

Indications

• Routine cervical cancer screening in all sexually active women aged 21-65
• Follow-up of previously treated CIN or cervical cancer
• Women with abnormal vaginal discharge or post-coital/intermenstrual bleeding (diagnostic use)
• Before starting OCP in some protocols
• Post-radiation surveillance

Technique

1. Avoid sampling during menstruation; ideally mid-cycle
2. Patient should not have douched, used vaginal medications, or had intercourse for 24-48 hours prior
3. Patient placed in dorsal lithotomy position
4. Cusco's bivalve speculum inserted without lubricant (lubricant may obscure cells)
5. Cervix visualized; discharge gently removed with cotton swab
6. Ayre's spatula placed with longer end in external os, rotated 360° - samples squamocolumnar junction (transformation zone)
7. Endocervical brush inserted into canal and rotated 180-360°
8. Cells spread on a labeled glass slide (or rinsed in liquid vial for LBC)
9. Slide immediately fixed with 95% ethanol spray/immersion
10. Sent to lab with completed request form (patient details, LMP, clinical findings)

* FIGO Staging of Cervical Cancer (GMC - 4 marks)

Note: In the 2018 updated FIGO staging, lymph node involvement was added as Stage IIIC (previously staging was purely clinical). Imaging (CT, MRI, PET) and pathology can now be used to assign stage.

• This patient's lesion (4×3 cm) = Stage IB2 (2018) or IB1 (2009 staging)
• Stage I = cervix only; Stage II = beyond cervix but not sidewall; Stage III = sidewall/lower vagina; Stage IV = bladder/rectum/distant
• The most common histological type is Squamous Cell Carcinoma (80%); adenocarcinoma accounts for ~15%
• HPV 16 and 18 cause ~70% of all cervical cancers
• Post-coital bleeding is the classic presenting symptom of early invasive cervical cancer