Invasive cervical cancer

Last updated: October 19, 2023

Summarytoggle arrow icon

Cervical cancer is the third most common cancer of the female genital tract in the US, with a peak incidence in women between 35–44 years of age. Persistent infection with any high-risk HPV genotype is the most common cause of cervical cancer. Consequently, the main risk factors are those that increase the likelihood of contracting HPV infection (e.g., multiple sexual partners) and/or decrease the clearance of ongoing infection (e.g., immunosuppression). Early-stage cervical cancer is typically asymptomatic. Symptoms, such as abnormal vaginal bleeding, dyspareunia, and pelvic pain, usually manifest later in the disease course. Diagnostics for individuals with concerning symptoms include colposcopy with cervical biopsy. Once the diagnosis is confirmed, invasive cervical cancer should be staged (FIGO staging for cervical cancer is preferred) to determine the appropriate treatment and likely prognosis. Surgery (e.g., conization, trachelectomy, hysterectomy) may be appropriate for early-stage disease. Management options for advanced disease include concurrent chemoradiotherapy, systemic chemotherapy, and palliative radiotherapy. Management of pregnant individuals with invasive cervical cancer or precancerous lesions should be individualized. Patients with invasive cervical cancer should be closely followed up for recurrence after management. HPV immunization, counseling on safe sex practices, and screening for cervical cancer are the most effective prevention measures.

Cervical cancer screening and management of precursor lesions are detailed in a separate article.

Epidemiologytoggle arrow icon

One in 161 female individuals in the US (∼ 0.6%) will develop cervical cancer during their lifetime. [1]

Cervical intraepithelial neoplasia (CIN), a precursor of cervical cancer, typically occurs in young adults (25–35 years).

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Human papillomavirus virus (HPV) infection [4][5][6]

Risk factors [4]

The most common risk factors for cervical cancer are those that increase the likelihood of HPV infection (e.g., multiple sexual partners) and/or decrease the clearance of ongoing infection (e.g., immunosuppression). [4]

Immunocompromised individuals, those who were exposed to DES in-utero, and those with a current or past history of a high-grade precancerous cervical lesion are considered to have a high risk of developing invasive cervical cancer. Screening modalities and intervals in these groups of individuals should account for the increased risk (see “Screening recommendations for individuals at high risk of cervical cancer”). [9][10][11]

Clinical featurestoggle arrow icon

Cervical cancer is usually asymptomatic in the early stages; symptoms typically develop later in the course of the disease.

Always consider cervical cancer as a cause of postcoital bleeding.

Diagnosticstoggle arrow icon

Invasive cervical cancer is confirmed on colposcopy with biopsy and histological evaluation. Diagnosis of cervical cancer precursor lesions is detailed in “Cervical cancer screening”.

Colposcopy [12][13] [14][15]

Indications [12][13][14]


Overview of colposcopy findings [12][14][15]
Features of epithelium
Features suggestive of precancerous lesions [12][14]
  • Acetowhitening (most common): an area that appears white after the application of acetic acid
Features suggestive of invasive cervical cancer
  • Cervical leukoplakia: a white membrane on the cervix that cannot be scraped off [6]
  • Erosion
  • Friable tissue

The cervical transformation zone or squamocolumnar junction is the most common site for squamous cell carcinoma and its precursors and should always be evaluated during colposcopy. Failure to do so may cause cervical cancer or precancerous lesions to be missed. [15]

Cervical punch biopsy [11][12][13][14][16]

  • Indications and procedure [12][14]
  • Findings: See “Pathology” section. [6][17]

Nontargeted (random) biopsies are not recommended in individuals with normal findings on colposcopy who are at low risk for CIN (i.e., HPV negative and cytology less than HSIL). [12][14]

Expedited treatment (without a preceding biopsy) is recommended for asymptomatic women at high risk of CIN3 with normal findings on colposcopy. Observation is recommended for women with normal colposcopy findings who are at very low risk of CIN. [11][13]

Pathologytoggle arrow icon

Squamous cell carcinoma (∼ 80% of cases) [18]

Adenocarcinoma (∼ 20% of cases) [20]

Clear-cell carcinoma of the cervix (CCC) [21]

Atypical columnar epithelium with elongated nuclei

Almost all squamous cell carcinomas and approx. 90% of adenocarcinomas of the cervix are positive for HPV. [6]

Cervical carcinoma and HSIL most commonly arise from metaplastic squamous cell epithelium in the cervical transformation zone. [6]

Stagingtoggle arrow icon

Determination of stage [5][26][27]

Refer patients with confirmed invasive cervical cancer to a specialist (e.g., gynecologic oncologist, surgical oncologist) for staging. Staging is based on the following parameters. [5]

Assessment of the primary tumor and lymph node involvement on imaging and/or intraoperatively is not mandatory for cervical cancer staging. In resource-poor settings, staging can be based on clinical examination and diagnostic histopathology results. [26]

Histopathological assessment and imaging are adjuncts to clinical findings in assessing the pretreatment stage of invasive cervical cancer. Histopathological findings take precedence over imaging findings. [5][26]

FIGO staging of cervical cancer [5][26][27]

FIGO staging of cervical cancer (2018) [5][26][27]
Tumor location and spread
  • Tumor strictly confined to the cervix
    • IA: microscopic stromal invasion ≤ 5 mm
    • IB: gross or microscopic stromal invasion > 5 mm in depth
  • Extension beyond the uterus but does not involve the pelvic wall or lower third of the vagina
    • IIA: upper two-thirds of the vagina, no parametrial invasion
    • IIB: with parametrial invasion

If there is any discrepancy in staging, the lower stage should be assigned. [26]

Treatmenttoggle arrow icon

Management of invasive cervical cancer in nonpregnant individuals is described here. Management of cervical cancer precursors and management of invasive cervical cancer during pregnancy are detailed separately. [5]

Early disease (FIGO stages IA, IB1, IB2 IIA1)

Locally advanced disease (FIGO stages IB3, IIA2, III, IVA)

Distant metastases (FIGO Stage IVB)

  • CCRT may be considered depending on the likely prognosis.
  • Palliative radiotherapy and/or systemic chemotherapy can be considered for symptom control.

Prior to surgery, patients who opt for fertility-preserving options should be counseled on potential postoperative obstetric complications and be referred to a fertility specialist to discuss future reproductive plans. [5][30]

Consider hormone replacement therapy for patients < 50 years of age who have lost ovarian function. [5]

Follow-up [5]

  • General principles
    • A thorough clinical examination and history should be taken at each follow-up visit.
    • Imaging is not routinely indicated.
  • After treatment for invasive cervical cancer: Follow-up is recommended at the following intervals.
    • Every 3–4 months for 2–3 years
    • Followed by every 6 months for 3–5 years
    • Then annually for life
  • After fertility-sparing surgery for microinvasive cancer: Resume routine age-appropriate screening for cervical cancer if follow-up testing is negative for 5 consecutive years.

Surgical interventions for cervical cancertoggle arrow icon

Conization (cervical excisional procedure) [31]

A fertility-preserving diagnostic and therapeutic procedure in which a cone-shaped portion of the cervix including the ectocervix, endocervix, and cervical transformation zone are excised

  • Indications [5][11]
    • Treatment of high-grade cervical abnormalities on screening
    • Treatment of early-stage cervical cancer
  • Important contraindications include pregnancy and severe cervicitis [11]
  • Methods
    • Cold-knife conization
      • A scalpel is used to remove a cone-shaped portion of cervical tissue.
      • Typically requires general or regional anesthesia
    • Loop electrosurgical excision procedure (LEEP)
      • A thin electric wire loop is used to remove abnormal cervical tissue.
      • Can be performed under local anesthesia as an office procedure
    • Laser conization
  • Common complications: bleeding, infection, obstetric complications (preterm delivery) [31]

LEEP is usually the preferred method of conization. [11]

Radical trachelectomy [30]

A surgical procedure that includes removal of the cervix, upper vagina, and parametrium with or without bilateral pelvic lymphadenectomy; followed by anastomosis of the uterus and vagina. [5][30]

Hysterectomy [5]

  • Types
  • Indication (for cervical cancer): early-stage disease
  • Approach: laparotomy, laparoscopy, or robotic surgery through a transabdominal or transvaginal approach
  • Complications include: bleeding, infections, and injury to surrounding organs (e.g., ureter, bladder, pelvic nerves) [32]

Pelvic exenteration (gynecology)[33]

A radical procedure that involves an en bloc resection of the uterus, ovaries, fallopian tubes, vagina, the lower urinary tract, rectosigmoid, and pelvic lymph nodes. Associated with high morbidity.

Special patient groupstoggle arrow icon

Management of invasive cervical cancer during pregnancy [5]

  • Treatment should be individualized and carried out by a multidisciplinary team (e.g., gynecologic oncologist, maternal-fetal specialist).
  • Treatment options are the same as those for nonpregnant individuals (see “Treatment of cervical cancer” for details).
  • The timing of treatment depends on the cancer stage, gestational age, and the patient's wish to maintain the current pregnancy.
Treatment of invasive cervical cancer during pregnancy [5]
< 20 weeks' gestation
  • Consider treatment without delay.
> 20 weeks' gestation

Early stage

(FIGO stages IA1, IA2, IB1, IB2)

  • Consider delaying treatment until the postpartum period.
  • Early delivery (within the 34th week of gestation) can be considered to facilitate earlier treatment.
Advanced stage

Complicationstoggle arrow icon

Direct complications of invasive cervical cancer

Complications of radiation therapy [36]

We list the most important complications. The selection is not exhaustive.

Prognosistoggle arrow icon

  • Cervical cancer has the best prognosis out of the three main gynecological cancers (ovarian, endometrial, and cervical cancer).
  • The survival rates decrease with increasing FIGO stage [38]
    • Stage 0: > 93%
    • Stage I: 93%
    • Stage II: 63%
    • Stage III: 35%
    • Stage IV: 16%
  • Patients without lymph node involvement have a very good prognosis, regardless of FIGO stage.
  • Main cause of death: uremia, often occurs secondary to bilateral ureteral obstruction.

Preventiontoggle arrow icon

Referencestoggle arrow icon

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