Cervical Cancer: Symptoms and Treatment

• Cervical cancer is detailed within obstetrics and gynaecology, Royal College of Surgeons in Ireland, oncology series

Knowledge Objectives

• Understanding the epidemiology is a key learning outcome
• Know how to classify cervical cancer by stage is important
• Being aware of the symptoms and signs of cervical cancer is essential
• Understanding how to investigate cervical cancer is crutial
• Knowing treatment options for cervical cancer is advantageous

Skills Objectives

• Provide counselling for patients newly diagnosed with cervical cancer
• Explain cervical cancer treatment options and their consequences for management

Epidemiology

• Cervical cancer is the fourth most common cancer in women, and fourth most common cause of death
• 70% of cervical cancer cases are from developing countries
• The incidence of cervical cancer has two peaks: in women in their 30s and in their mid-60s
• Since 1988 in the UK, the incidence of cervical cancer has decreased by 26%
• Since 1988 in the UK, mortality from cervical cancer has decreased by 50%, likely due to cervical screening

Development

• Cervical cancer develops from a progression of CIN (cervical intraepithelial neoplasia)
• 30% of women with CIN III, when it is left untreated, will develop invasive cancer over about 10-20 years
• Epidemiology is identical to that of CIN

Risk factors for Cervical Cancer

• HPV infection is responsible for 90% of cervical cancer cases
• Smoking
• Immunosuppression
• Starting sexual activity at a young age
• Having multiple sexual partners
• Using oral contraceptive pills
• Low socioeconomic status

Histology

• 85-90% are squamous cell carcinomas
• 10% are adenocarcinomas
• Adenosquamous carcinomas occur rarely

Histological features

• Increased nuclear cytoplasmic ratio
• Large nucleii
• Pleomorphic nucleii
• Invasion through basement membrane

Spread

• Local infiltration
  • Occurs laterally into parametrium in the commonest cases
  • Can lead to ureteric obstruction
  • Inferiorly into vagina
  • Superiorly into body of uterus
  • Anteriorly into bladder
  • Posteriorly into rectum
• Lymphatic spread
  • Occurs via the pelvic lymph node then into iliac and aortic nodes
  • Extent of lymphatic involvement correlates with disease stage
    • Stage 1: 10% positive nodes
    • Stage 3: 35% positive nodes

Early Disease Symptoms

• No symptoms (early stages)
• Vaginal bleeding, most commonly contact bleeding, including post-coital, intermenstrual, or postmenopausal bleeding
• Bloody and offensive vaginal discharge
• Dyspareunia (pain with sex)
• Vaginal mass

Advanced Disease Symptoms

• Symptoms due to spread of disease to distant organs
• Loss of appetite
• Weight loss
• Pelvic pain
• Pain referred to legs and back
• Leg swelling
• Anuria and renal failure due to bilateral ureteric obstruction
• Heavy vaginal bleeding

Clinical Findings

• Hard, irregular enlarged and possibly ulcerated cervix which bleeds on contact with speculum exam or bimanual exam

Diagnosis

• A full history and clinical examination are needed
• Perform colposcopy and biopsy if referral cytology is suspicious
• Intense acetowhiteness, atypical vessels, raised or ulcerated surface, and contact bleeding are suspicious features during colposcopy
• Diagnosis is based on histology and appropriate biopsies

Staging

• Involves examination under anaesthetic with combined rectovaginal examination
• Biopsy of suspicious areas are needed
• Cystoscopy and sigmoidoscopy may be considered
• Chest x-ray and intravenous urogram are performed

CT and MRI

• Are required to assess:
  • CT scan detects issues in the chest & abdomen, and para-aortic nodes
  • MRI is best for pelvic soft tissue
  • Spread of disease within the pelvis
  • Enlarged lymph nodes
  • Liver metastatic disease

Stages

• Stage I: Confined to the cervix
• Stage II: Extends beyond the cervix, but not to the pelvic side wall, and/or extends into the upper two-thirds of the vagina
• Stage III: Extends to the pelvic sidewall and/or the lower third of the vagina
• Stage IV: Extends beyond the true pelvis or involves the bladder or rectum

Stage I Details

• Stage Ia1: Depth of invasion is less than 3mm, and the width is less than 7 mm
• Stage 1a2: Depth of invasion between 3 and 5 mm, and width less than 7 mm
• Stage 1b1: Tumour is confined to the cervix, and the diameter is less than 4 cm; microscopic tumour greater than 7mm width and macroscopic tumours
• Stage 1b2: Tumour is confined to cervix and diameter is greater than 4cms

Stage II details

• Stage IIa: No parametrial spread
• Stage IIb: Obvious parametrial spread

Stages III & IV Details

• Stage III: Tumour has grown into the walls of the pelvis and/or is blocking one or both ureters, causing kidney problems (hydronephrosis)
• Stage IV: Tumour has spread to the bladder or rectum, or its growing out of the pelvis

Treatment of Stage Ia

• Microscopic disease
• Cone biopsy with regular smears and colposcopy is performed if the patient wishes to preserve fertility
• If her family is complete, normal treatment is a simple hysterectomy

Treatment of Stage IB1

• Options include radical surgery or radical radiotherapy
• Survival rates using either method are similar
• Radiotherapy has significant morbidity association

Radical Hysterectomy

• This is also known as Wertheim Hysterectomy
• It involves a total abdominal hysterectomy, removal of parametria, the upper third of the vagina, and pelvic lymph nodes
• Involves conservation of ovaries in younger women
• Radical Hysterectomy involves higher morbidity than simple hysterectomy

Radical Radiotherapy

• This is a combination of external beam therapy and local vaginal therapy

External beam therapy (Teletherapy)

• Involves aiming to treat lymph nodes
• Involves repeated treatments over 6 weeks

Local vaginal therapy (Brachytherapy)

• Is designed to treat central disease
• The vaginal source of radiation is left in situ for 12-18 hours
• Radical Radiotherapy morbidity includes vaginal dryness and stenosis, dyspareunia, cystitis, proctitis, and premature menopause

Treatment of Stage Ib2 to IVa

• Chemoradiotherapy is the primary treatment
• Surgery has no role
• Radical radiotherapy aims to cure
• Palliative radiotherapy is for symptom control, mainly pain

Treatment of Stage IVb

• Treatment is individualized based on the location and extent of disease

Recurrent Disease

• Cases of pelvic recurrence are considered for modality of treatment when prior modalities were not utilized
• Radiotherapy is not effective if patient previously had radiotherapy
• Pelvic exenteration should be considered for surgical candidates and includes removal of the vagina, uterus with bladder and rectum

Survival

• Survival rates vary based on the stage of cervical cancer
  • Stage Ia1 has a 90% 5-year survival rate
  • Stage Ia2-Ib2 carries an 85% 5-year survival rate
  • Stage II cases, the 5-year survival rate is 60%
  • Stage III has a 40% 5-year survival rate
  • Stage IV has a 15% 5-year survival rate