Cervical Carcinoma Notes

General Description

  • Cervical cancer is the third most common malignancy of the female genital tract.
  • It is the second most common cancer in women worldwide after breast cancer.
  • It is a malignant epithelial disease in the cervical gland of the uterus, also called cervical intraepithelial neoplasia.

Risk Factors

  • Human papillomavirus (HPV) is the most common risk factor.
  • Other factors increasing risk of STI include:
    • Coitus before 18 years of age
    • Multiple sex partners
    • Multiparity
    • Poor personal hygiene and poor socio-economic status
    • Smoking
    • OCP (Oral Contraceptives)
  • Prolonged use of OCP, especially at a young age, increases the risk of adenocarcinoma of the endocervix.
  • In utero exposure to diethylstilbestrol (DES).
  • High-risk HPV types: 16, 18 (70% of CIN and cervical cancer, Type 18 more specific to endocervix).
  • Low-risk HPV types: 6, 11 (anogenital warts, condyloma acuminata, laryngeal papillomatosis of the newborn).
  • Age: Bimodal distribution (first peak: 35-39 years, second peak: 60-65 years).
  • Mean age: 52.2 years.

Pathophysiology

  • HPV infection leads to persistent infection.
  • HPV DNA integrates into host DNA.
  • Oncoproteins are synthesized, leading to dysplastic vaginal epithelial cells, CIN, and eventually cancer.

Histological Subtypes

  • Squamous cell carcinoma (80-90%), arising from the squamo-columnar junction, better prognosis.
    • Large cell keratinizing type (most common).
    • Small cell (poor prognosis).
  • Adenocarcinoma.
  • Mixed.

Clinical Features - Symptoms

  • Asymptomatic (less than 5%).
  • Abnormal vaginal bleeding (pre or postmenopausal, minimal or non-persistent).
  • Abnormal vaginal discharge (25%).
  • Post-coital bleeding.
  • Pelvic pressure or discomfort.

Clinical Features - Signs

  • No evidence in early stage.
  • Slight enlargement of cervical size and soft.
  • Fixed, immobile uterus, adenexal mass in advanced stage.

Special Examinations

  • Punch biopsy (D & C): Most effective, definitive procedure.
    • Establishes correct diagnosis and clinical stage.
    • Differentiates from cervical cancer or cervical involvement.
  • Colposcopy: Direct observation for taking samples correctly, identifying growth and staging.
  • Pap test: Unreliable diagnostic test (30-50% abnormal results).
    • Start at 21 years, interval 3 years. HPV DNA testing beyond 30 years, interval 5 years.

Diagnosis

  • History, clinical signs, related risk factors, and symptoms.
  • Diagnostic methods.

Differential Diagnosis

  • Senile endometritis / vaginitis.
  • Dysfunctional uterine bleeding.
  • Submucous myoma / endometrial polyps.
  • Cervix cancer / sarcoma of uterus / primary carcinoma of fallopian tube.

Metastasis Routes

  • Direct extension.
  • Lymphatic metastasis (important route).
  • Hematogenous metastasis.

Clinical Stages (FIGO 1971)

  • Stage I: Carcinoma confined to the cervix.
    • Ia: Length of uterine cavity ≤ 2 cm.
    • Ib: Length of uterine cavity > 4 cm.
  • Stage II: Carcinoma involves corpus and cervix, but not outside the uterus.
  • Stage III: Carcinoma extends outside the uterus, but not outside the true pelvis.
  • Stage IV:
    • IVa: Carcinoma extends outside the uterus and involves mucosa of bladder or rectum.
    • IVb: Carcinoma extends outside the true pelvis and spreads to distant organs.

Surgical Pathologic Staging (FIGO 1988)

  • Stage I: Tumor confined to the cervix.
  • Stage II: Tumor limited to the upper 2/3 of the vagina; parametrium but not to the lateral pelvic walls.
  • Stage IIIA: Lower 1/3 of the vagina.
  • Stage IIIb: Parametrium up to the lateral pelvic wall.
  • Stage IIIC: Pelvic and para-aortic nodes.

Treatment

  • Surgery, radiation, chemotherapy.
  • Early stage: Surgery + postoperative adjuvant therapy.
  • Advanced stage: Radiation + surgery + medicine.

Principles of Choice

  • General condition (age, complication).
  • Clinical stage.
  • Tumor pathologic type.

Surgery

  • Objective: Operative pathologic stage, finding prognosis risk factors, remove uterus and metastasis tumor.
  • Stage I: Abdominal hysterectomy (simple or conization), salpingo-oophorectomy +/- selective lymphadenectomy; Clear cell or papillary carcinoma – omentectomy + appendectomy.
  • Stage II: Radical hysterectomy + pelvic lymphadenectomy + para-aortic lymphadenectomy.
  • Stage III, IV: Cytoreductive surgery.

Indications of Pelvic Lymphadenectomy

  • Special pathogenetic pattern, CERVICAL, grade 3 or no differentiation.
  • Myo-invasion more than ½.
  • Involvement in isthmus of uterus.

Radiation Therapy

  • If radiation size is less than 4 cm, treatment choice is chemo-radiation; both are effective.
  • In cervical surgery, ovaries are preserved; in radiation therapy, ovaries are removed.
  • Chemotherapy is a radiation sensitizer.

Post-Operative Management

  • Histopathological report.
  • Margins of specimens.
  • Mets to lymph nodes and parametrium.
  • Than we have to start chemo radiation.
  • Poor prognostic factors.

Indications for Radiation Alone

  • Elderly or obesity.
  • Multiple chronic or acute medical illnesses (hypertension, cardiac disease, diabetes, pulmonary, renal).
  • Advanced stage unsuitable for surgery.

Hormone Therapy

  • Stage 1b1: Fertility sparing surgery (Conization, simple hysterectomy, Radical trachelectomy - cervix is removed, parametrium and is removed, and sutured to the vagina).

Chemotherapy

  • Advanced stage or recurrent carcinoma.
  • Postoperative adjunctive treatment for high-risk factors.
  • Drugs used: DDP (cisplatin) is the drug of choice.

Follow-Up

  • Main complaints, pelvic examination, vaginal discharge smear.
  • Chest X-ray, serum CA125, blood routine test, blood biochemistry examination, CT/MRI.