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 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.
- Incidence: 7.4:100,000 
- Peak incidence: 35–44 years of age 
- Mortality: 2.2:100,000 women per year 
One in 161 female individuals in the US (∼ 0.6%) will develop cervical cancer during their lifetime. 
Epidemiological data refers to the US, unless otherwise specified.
Human papillomavirus virus (HPV) infection 
- Infection with genotypes is the main cause of cervical cancer.
- Nearly all squamous cell carcinoma of the cervix and approximately 90% of adenocarcinoma of the cervix are positive for HPV infection. 
- The major high-risk HPV types are HPV 16 and HPV 18. 
Risk factors 
- For contracting HPV infection
- Environmental risk factors
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). 
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”). 
Cervical cancer is usually asymptomatic in the early stages; symptoms typically develop later in the course of the disease.
- Early symptoms
- Late symptoms: hydronephrosis, lymphedema, fistula formation
- Cervical examination: ulceration, induration, or an exophytic tumor (see “Overview of colposcopy findings”)
Always consider cervical cancer as a cause of postcoital bleeding.
Colposcopy  
- Individuals with
- Abnormal findings on pelvic examination
- Asymptomatic individuals with immediate risk of CIN3 ≥ 4% on cervical cancer screening who do not meet the threshold for or do not wish to undergo expedited treatment
- Certain results on (see “Exceptions to the risk-based approach”)
|Overview of colposcopy findings |
|Features of epithelium|
|Features suggestive of precancerous lesions |
|Features suggestive of invasive cervical cancer|
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. 
Cervical punch biopsy 
Indications and procedure 
- Abnormal colposcopy findings: Obtain multiple (2–4) colposcopy-directed biopsies targeting all areas of cervical abnormalities (e.g., acetowhitening, metaplasia) and the squamocolumnar junction. 
- Normal colposcopy findings in individuals at high risk of CIN3 who do meet the threshold for or do not wish to undergo expedited treatment: Consider random, nontargeted biopsies OR biopsy the squamocolumnar junction.
- Findings: See “Pathology” section. 
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. 
- Invasive cervical carcinoma is characterized by invasion of the tumor beyond the basement membrane of the cervical epithelium.
- HSIL and invasive cervical carcinoma most commonly arise from metaplastic squamous cell epithelium in the cervical transformation zone (see “Microscopic anatomy of the cervix” in “” for more information on the histology of the cervix).
Squamous cell carcinoma (∼ 80% of cases) 
- Subtypes include large cell keratinizing, large cell nonkeratinizing, and papillary squamous cell carcinoma.
- Irregular cell morphology
- Hyperchromatic cells with nonspherical nuclei, mitotic activity, and prominent nucleoli
- Loss of basal membrane
- Precursor lesion: CIN or SIL 
Adenocarcinoma (∼ 20% of cases) 
- Subtypes include mucinous, endometrioid, clear-cell, and serous adenocarcinoma
- The most common is the endocervical mucinous subtype
- Precursor lesion: endocervical adenocarcinoma in situ 
Clear-cell carcinoma of the cervix (CCC) 
- Rare form of cervical cancer (∼ 4% of all cervical adenocarcinomas)
- Frequently associated with exposure to diethylstilbestrol (DES).
Atypical columnar epithelium with elongated nuclei
- Small-cell carcinoma: ∼ 2% of cases 
Staging of invasive cervical cancer is based on the extent of the primary tumor and spread; routes of spread include: 
- Direct extension into the vagina, uterus, parametrium, pelvic wall, and adjacent organs (e.g., bladder, rectum)
- Lymphatic spread, first to the regional pelvic lymph nodes, and then to the paraaortic lymph nodes.
- Hematogenous spread causing distant metastases (e.g., to lungs, liver, bone) occurs late in the course.
- The revised (2018) FIGO staging is preferred to determine the appropriate treatment of cervical cancer and the likely prognosis of the disease. 
- FIGO staging aligns closely with the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging. 
- The TNM classification also includes a stage 0 (Tis) for carcinoma in situ (CIN III). 
Determination of stage 
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. 
- Clinical examination: comprehensive physical exam, , colposcopy
- Cervical biopsy and lymph node biopsy findings
- Imaging 
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. 
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. 
FIGO staging of cervical cancer 
|FIGO staging of cervical cancer (2018) |
|Tumor location and spread|
If there is any discrepancy in staging, the lower stage should be assigned. 
Management of invasive cervical cancer in nonpregnant individuals is described here.and are detailed separately. 
Early disease (FIGO stages IA, IB1, IB2 IIA1)
Surgery is preferred.
- Conization (with or without pelvic lymphadenectomy) and radical trachelectomy are fertility-sparing options.
- Hysterectomy (simple hysterectomy, modified radical hysterectomy, and radical hysterectomy) with bilateral pelvic lymphadenectomy is usually recommended for more advanced disease (stage ≥ IA2)
- If surgery is not feasible: Radiotherapy may be considered.
Locally advanced disease (FIGO stages IB3, IIA2, III, IVA)
- Concurrent chemoradiotherapy (CCRT) using is preferred.
- Pelvic exenteration may be considered in select patients with stage IVA cervical cancer that has not extended to the pelvic side wall.
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. 
Consider hormone replacement therapy for patients < 50 years of age who have lost ovarian function. 
- 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 cancer
Conization (cervical excisional procedure) 
- Treatment of high-grade cervical abnormalities on screening
- Treatment of early-stage cervical cancer
- Important contraindications include pregnancy and severe cervicitis 
- 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
- Cold-knife conization
- Common complications: bleeding, infection, obstetric complications (preterm delivery) 
Radical trachelectomy 
- Indication: fertility-sparing procedure for early-stage cervical cancer 
- Complications include: 
- Simple hysterectomy: removal of the uterus and cervix; vagina and parametrium are preserved
- Modified radical hysterectomy: en bloc removal of the uterus, cervix, upper ¼ of the vagina, and the parametrium
- Radical hysterectomy: en bloc removal of uterus, cervix, upper ⅓ to upper ½ of the vagina, the parametrium , and, if needed, resection of involved aspects of the adjacent organs
- 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) 
Pelvic exenteration (gynecology)
Special patient groups
Management of invasive cervical cancer during pregnancy 
- 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 |
|< 20 weeks' gestation|| |
|> 20 weeks' gestation|| |
(FIGO stages IA1, IA2, IB1, IB2)
Direct complications of invasive cervical cancer
- Local infiltration of organs
- Fistula formation in locally advanced disease (e.g., rectovaginal, vesicovaginal, urethrovaginal fistula)
- Compression of veins or lymphatic vessels in the lesser pelvis → lymphedema of the lower extremities
- Metastasis 
- CACS) ( 
- Vaginal stenosis
- Postirradiation vaginitis (e.g., vaginal dryness, dyspareunia)
- Radiogenic cystitis/proctitis
- Radiation may increase the risk of complications like fistula formation. 
We list the most important complications. The selection is not exhaustive.
- 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 
- 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.