Cervical Cancer

Background

• Cervical cancer is a malignancy originating in the transformation zone of the cervix, most commonly in squamous cells.
• It is the second most common cancer in women worldwide, and the third most common cause of female cancer mortality.
• Types of cervical cancer include squamous cell carcinoma (most common), invasive adenocarcinoma, small cell neuroendocrine carcinoma, and other rare histologic types.
• There is a causal link with persistent infection with oncogenic types of human papillomavirus (HPV), most commonly HPV-16 and HPV-18, which are sexually transmissible pathogens.
• Cervical cancer is the result of a progression of epithelial changes from cervical intraepithelial neoplasia (CIN) 1 to CIN 2 and CIN 3, finally resulting in invasive cervical cancer. Regression of CIN can occur, with higher rates of regression seen with lower grades of CIN.

Evaluation

• Early stage disease is usually asymptomatic and detected by screening with cervical smear.
• Symptoms, if present, are usually vaginal bleeding or blood-stained vaginal discharge.
• Diagnosis is usually made using colposcopically directed cervical biopsy.
• Imaging should be done for clinical staging and risk assessment (Strong recommendation).

Management

• Treatment plan is based on clinical staging (International Federation of Gynecology and Obstetrics [FIGO] staging and radiologic assessment of disease) including nodal status and histological biopsy results (Strong recommendation).
• For early invasive cancer (small tumors ≤ 4 cm confined to cervix) initial treatment is surgery or radiation (Strong recommendation).
  • Consider radical trachelectomy with pelvic lymphadenectomy with or without para-aortic lymphadenectomy, with possible sentinel lymph node (SLN) mapping for patients desiring fertility-sparing (Weak recommendation).
  • Surgery for patients not desiring fertility-sparing, should include radical hysterectomy with pelvic lymphadenectomy (Strong recommendation) with or without para-aortic lymphadenectomy (Weak recommendation), with possible SLN mapping.
  • For patients who have surgery, indications for chemoradiation include positive margins, parametrial involvement, or pelvic node involvement.
  • Offer adjuvant radiation therapy for patients who have negative nodes, negative margins, negative parametrium, and a combination of risk factors that meet Sedlis criteria (Strong recommendation).
• Treatment for locally advanced cancers (FIGO stage IB3 tumors and higher):
  • For stage IB3-IVA:
    • Offer definitive pelvic external beam radiation therapy (EBRT) plus brachytherapy with concurrent platinum-containing chemotherapy if negative adenopathy on imaging and negative node status on surgical staging (Strong recommendation).
    • For stage IB3 and stage IIA2, consider any of the following options:
      • pelvic EBRT plus concurrent platinum-containing chemotherapy plus brachytherapy (Strong recommendation)
      • radical hysterectomy with pelvic lymphadenectomy with or without para-aortic lymphadenectomy (Weak recommendation)
      • pelvic EBRT plus concurrent platinum-containing chemotherapy, brachytherapy, and selective completion hysterectomy (Weak recommendation)
  • For stage IVB:
    • If disease is amenable to local treatment, consider local treatment with or without adjuvant chemotherapy (Weak recommendation). Local treatment options include the following:
      • resection with or without individualized pelvic EBRT
      • local ablative therapies with or without individualized EBRT
      • individualized EBRT with or without chemotherapy
    • If disease is not amenable to local treatment, consider chemotherapy or best supportive care (Weak recommendation).
• Treatment of locoregional and metastatic recurrence:
  • If disease is amenable to local treatment, consider local treatment with or without adjuvant chemotherapy (Weak recommendation). Local treatment options include the following:
    • resection with or without individualized pelvic EBRT
    • local ablative therapies with or without individualized EBRT
    • individualized EBRT with or without chemotherapy
  • If disease is not amenable to local treatment, consider chemotherapy or best supportive care (Weak recommendation).
• Treatment of small cell neuroendocrine carcinoma of the cervix:
  • If disease is confined to the cervix and tumor is ≤ 4 cm, consider either of the following: (Weak recommendation)
    • radical hysterectomy with pelvic lymphadenectomy (preferred if suitable for primary surgery) with or without para-aortic lymph node sampling
    • chemoradiation (concurrent platinum-containing chemotherapy with EBRT using cisplatin/etoposide or carboplatin/etoposide if cisplatin-intolerant) with brachytherapy, and additional chemotherapy if adjuvant treatment is required
  • If disease is confined to the cervix and tumor is > 4 cm, consider either of the following (Weak recommendation):
    • chemoradiation (concurrent platinum-containing chemotherapy with EBRT using cisplatin/etoposide or carboplatin/etoposide if cisplatin-intolerant) plus brachytherapy, with additional chemotherapy if adjuvant treatment is required
    • neoadjuvant chemotherapy (cisplatin/etoposide or carboplatin/etoposide) with or without interval hysterectomy
• Options for pregnant patients with cervical cancer include:
  • delayed treatment until documented fetal maturity, which involves either of the following (Strong recommendation):
    • concurrent radical hysterectomy and pelvic node dissection during cesarean section
    • radiation therapy with or without chemotherapy (traditional treatment protocols may need to be modified)
  • immediate treatment based on disease stage (Strong recommendation)
• Approach to cervical cancer survivors should include regular general medical care, assessment of late and long-term effects of cervical cancer, postradiation use of vaginal dilators and moisturizers, communication and coordination with all clinicians involved in care, including primary care clinicians, and summary of treatment and follow-up recommendations (Strong recommendation).