Cervical cancer

Summary

Cervical cancer arises from neoplastic changes in the cervix, often developing over 10–20 years from cervical intraepithelial neoplasia (CIN), primarily due to persistent infection with high-risk human papillomavirus (HPV), especially types 16 and 18. It is most common in women under 47, with a peak incidence at ages 25–29 and a second peak in older women. Risk factors include early sexual activity, multiple partners, smoking, long-term contraceptive use, and immunosuppression. Most cases are squamous cell carcinoma, with symptoms like abnormal vaginal bleeding, discharge, or pelvic pain. Diagnosis involves colposcopy and biopsy, with staging via imaging and FIGO criteria. Management depends on stage and includes surgery, chemoradiation, or palliative care. Screening and HPV vaccination have significantly reduced incidence.

Definition

Cervical cancer arises from neoplastic changes in the cervix; the lower portion of the uterus. Globally, it ranks as the third most common cancer among women. It is a cancer that predominantly affects younger women:

• 50% of cases are diagnosed before age 47

• Peak incidence is observed in women aged 25–29

• A second peak occurs in women over 80

Note: Screening and vaccination have drastically reduced incidence 

Aetiology and Pathophysiology

Types of Cervical Cancer:

• Squamous cell carcinoma: ~ 80% of cases

• Adenocarcinoma

• Small cell carcinoma: worst prognosis

Cervical cancer often evolves from cervical intraepithelial neoplasia (CIN) over 10–20 years. Not all CIN cases progress; many regress spontaneously.

Invasive cancer occurs when the basement membrane is breached, enabling metastasis to the lungs, liver, bone, and bowel.

Role of HPV

• Most of cervical cancers contain HPV DNA

• HPV is a sexually transmitted DNA virus affecting mucosal tissues

• High-risk types (16, 18, 31, 33, 35) are oncogenic

• Low-risk types (6, 11) cause benign lesions like genital warts

• High-risk HPV strains inhibit tumor suppressor protein p53, promoting dysplasia and malignancy.

Risk Factors

• Persistent HPV infection (primary risk factor)

• Early sexual activity

• Multiple sexual partners

• Smoking

• Long-term oral contraceptive use (>8 years)

• Immunosuppression (e.g., HIV)

• Nutritional deficiencies (Vitamins A, C, E, folic acid)

• Exposure to DES (linked to adenocarcinoma)

Clinical Presentation

Symptoms

• Abnormal vaginal bleeding: post-coital, intermenstrual, or postmenopausal (most common)

• Vaginal discharge: blood-stained or foul-smelling

• Dyspareunia, pelvic pain, weight loss

• Often asymptomatic in early stages

• Advanced signs: leg edema, flank pain, rectal bleeding, radiculopathy, haematuria

Examination

• Speculum exam: inspect for bleeding, discharge, or ulceration

• Bimanual exam: assess for pelvic masses

• GI and rectal exams: assess for organ involvement or metastasis

Investigations

Initial Evaluation

• Pre-menopausal women:

• Chlamydia testing first

• If negative or persistent symptoms: colposcopy and biopsy
  
  

• Post-menopausal women:

• Urgent colposcopy and biopsy

Colposcopy

• Uses a microscope to examine the cervix

• Acetic acid highlights dysplastic areas

• Biopsies are taken from suspicious regions
  
  

Staging Investigations

• Blood tests: FBC, LFTs, U&Es

• Imaging: CT chest-abdomen-pelvis, MRI pelvis, PET scan

• +/- Examination under anaesthesia (EUA)
  
  

Note: Cervical screening (Pap smear) detects pre-invasive disease (CIN) and is not diagnostic for cancer.

Staging (FIGO System)

• Stage 0: Carcinoma in situ (CIS)

• Stage I: Confined to cervix

• Ia: Microscopic only

• Ib: Clinically visible lesions

• Stage II: Extends beyond cervix (not to pelvic wall/lower third of vagina)

• Stage III: Involves pelvic wall or lower third of vagina, hydronephrosis

• Stage IV: Invades bladder, rectum, or distant metastases

Management

Surgical Options

• Stage Ia:

• Fertility desired: Radical trachelectomy

• Otherwise: Laparoscopic hysterectomy + pelvic lymphadenectomy

• Stage Ib/IIa:

• Radical (Wertheim’s) hysterectomy with lymphadenectomy

• Stage IVa/recurrent:

• Pelvic exenteration (anterior, posterior, or total)

Radiotherapy

• Used with/without chemotherapy

• Combination of external beam and brachytherapy

• Mainstay for stages Ib–III

• Chemoradiation is standard; hysterectomy adds no survival benefit

Chemotherapy

• Cisplatin-based regimens

• Neoadjuvant, adjuvant, or palliative use depending on stage

Follow-Up

• Every 4 months for 2 years, then every 6–12 months for 3 years

• Physical examination of vagina and cervix if present

• Pap smears not valid post-radiotherapy