Cervical Cancer

Symptoms

• Abnormal vaginal bleeding (between periods, after sexual intercourse, or after menopause)
• Heavier or longer menstrual periods than usual (menorrhagia)
• Unusual vaginal discharge (may be watery, bloody, or have a foul odor)
• Pelvic pain
• Pain during sexual intercourse (dyspareunia)
• Persistent back or leg pain (in advanced stages)
• Unexplained weight loss (in advanced stages)
• Fatigue (in advanced stages)
• Leg swelling (edema) (in advanced stages)
• Vaginal passage of urine or feces (fistula) (in advanced stages)
• Bone fractures (from metastases in advanced stages)
• Heavy or uncontrolled vaginal bleeding (emergency symptom)
• Severe pelvic or back pain (emergency symptom)
• Symptoms of kidney failure, such as decreased urine output or swelling (emergency symptom)

Causes & Risk Factors

• Persistent infection with oncogenic (high-risk) strains of Human Papillomavirus (HPV) is the primary cause for nearly all cases of cervical cancer.
• HPV types 16 and 18 cause approximately 70% of cervical cancers and pre-cancerous lesions.
• Other high-risk HPV types include 31, 33, 45, 52, and 58.
• HPV integrates its DNA into cervical cells, which can disrupt genes that normally control cell growth, leading to uncontrolled cell growth and cancer over many years.
• Most HPV infections are temporary and cleared by the immune system; cervical cancer develops only when a high-risk HPV infection persists for many years.
• Co-factors like smoking or a weakened immune system are often needed for persistent HPV infection to progress to cancer.
• Persistent infection with high-risk HPV types (HPV 16 and 18 are responsible for over 70% of cases)
• Weakened immune system (due to conditions like HIV infection or medications after organ transplant)
• Smoking (tobacco byproducts can damage cervical cell DNA and weaken the immune system's ability to fight HPV)
• Early age at first sexual intercourse (increases likelihood of HPV exposure)
• Multiple sexual partners (increases risk of HPV exposure)
• High parity (multiple full-term pregnancies, though the exact reason is not fully understood)
• Long-term use of oral contraceptives (more than 5 years; risk decreases after stopping)
• History of other sexually transmitted infections (STIs) like chlamydia, gonorrhea, and herpes simplex virus (may promote HPV persistence)
• Exposure to Diethylstilbestrol (DES) in utero (increases risk for a rare type of cervical cancer called clear cell adenocarcinoma)
• Age (most commonly diagnosed in women between 35 and 44)
• Genetic factors (family history may play a minor role, but evidence is weak)
• Smoking status (modifiable)
• Number of sexual partners (modifiable)
• Use of barrier contraception like condoms (can reduce but not eliminate risk, modifiable)
• Long-term oral contraceptive use (modifiable)
• HPV vaccination status (modifiable)
• HPV Vaccination (protective factor, highly effective in preventing infections with targeted HPV types)
• Consistent and correct condom use (protective factor, reduces risk of HPV transmission)
• Regular cervical cancer screening (protective factor, allows for detection and treatment of precancerous lesions)

Diagnosis

• Detailed medical history, including menstrual, obstetric, and sexual history, any abnormal screening tests, symptoms, and risk factors.
• Pelvic examination, including visual inspection of the cervix and vagina with a speculum, and bimanual palpation of the uterus, ovaries, and surrounding tissues.
• Rectovaginal examination to check for tumor spread.
• Colposcopy: A procedure using a magnifying instrument to examine the cervix, vagina, and vulva. Solutions like acetic acid or Lugol's iodine may be applied to highlight abnormal areas.
• Biopsy: Removal of a small tissue sample for examination under a microscope, which is the definitive diagnostic test.
• Punch biopsy (small tissue sample taken during colposcopy).
• Endocervical curettage (ECC) (cells scraped from the endocervical canal).
• Cone biopsy (conization) or LEEP (Loop Electrosurgical Excision Procedure) (removal of a larger, cone-shaped piece of tissue, which can be both diagnostic and therapeutic).
• Staging using the FIGO (International Federation of Gynecology and Obstetrics) system, which ranges from Stage I (confined to the cervix) to Stage IV (spread to distant organs).
• Magnetic Resonance Imaging (MRI) of the pelvis to evaluate tumor size, spread to surrounding tissues, and lymph node involvement.
• Positron Emission Tomography (PET) scan, often combined with CT (PET-CT), to detect cancer spread to lymph nodes or distant organs.
• Chest X-ray or CT scan of the chest to check for lung metastases.
• Ultrasound to check for kidney swelling (hydronephrosis) if tumor obstruction of the ureters is suspected.
• Definitive diagnosis is based on confirmation of invasive carcinoma from a cervical biopsy.
• Differential diagnosis considers other conditions such as precancerous lesions (CIN), cervicitis, cervical polyps, endometrial or vaginal cancer, and benign causes of abnormal bleeding.

Treatment Options

• For pre-invasive disease (CIN): Observation for low-grade lesions, excisional procedures (LEEP, cold knife conization), or ablative procedures (cryotherapy, laser ablation).
• For early-stage invasive cancer (Stage IA, IB1, IIA1): Surgery is the primary treatment.
• Cone biopsy for very small, microinvasive cancers (Stage IA1) when fertility preservation is desired.
• Radical trachelectomy (fertility-sparing surgery involving removal of the cervix, upper vagina, and surrounding tissues, with a cerclage placed).
• Radical hysterectomy with pelvic lymph node dissection (standard treatment, involves removal of the uterus, cervix, surrounding tissues, and upper vagina).
• Radiation therapy (external beam radiation therapy with or without chemotherapy, followed by brachytherapy) as an alternative to surgery for patients who are not surgical candidates.
• For locally advanced cancer (Stage IB2-IVA): Primary chemoradiation is the standard of care.
• External Beam Radiation Therapy (EBRT) to the pelvis.
• Concurrent platinum-based chemotherapy (e.g., cisplatin) to enhance the effect of radiation.
• Brachytherapy (internal radiation) boost to the cervix.
• For metastatic or recurrent cancer (Stage IVB and Recurrent): Systemic therapy.
• Chemotherapy (platinum-based regimens like cisplatin or carboplatin combined with paclitaxel).
• Targeted therapy (Bevacizumab, an anti-angiogenesis agent, may be added to chemotherapy).
• Immunotherapy (Pembrolizumab or cemiplimab, PD-1/PD-L1 inhibitors, may be used, especially for tumors that express PD-L1 or in the second-line setting).
• Palliative radiation to manage symptoms like bleeding or pain.
• Pelvic exenteration (a radical surgery for central pelvic recurrence in select patients without distant metastases).
• Regular follow-up appointments are critical to monitor for recurrence, typically every 3-6 months for the first 2 years, then every 6-12 months for years 3-5, then annually.
• Pap tests of the vaginal cuff may be performed during follow-up.
• Imaging may be used if recurrence is suspected.
• Any suspected or confirmed diagnosis of cervical cancer should be referred to a gynecologic oncologist for multidisciplinary team management.

Frequently Asked Questions