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Obstetrics and Gynecology›Condition·Updated Jun 21, 2026·v1

Cervical Cancer

Cervical cancer is a hrHPV-driven malignancy that is highly preventable through vaccination and screening. Management has evolved toward imaging-integrated FIGO staging, with a strict preference for open surgery in early stages and cisplatin-based CCRT for locally advanced disease. Immunotherapy has recently transformed the treatment of metastatic recurrence.

High Evidence410 references·1,131 words·5 min read·v1
gynecologic_oncologyHPVcervical_cancerFIGO_stagingimmunotherapy

Quick Reference

RxDrug of choiceCisplatin (for CCRT); Pembrolizumab + Platinum/Taxane (for metastatic)
AltAlternativesCarboplatin (if cisplatin-ineligible); Tisotumab vedotin (second-line metastatic)
⊘AvoidMinimally invasive radical hysterectomy (outside trials); Vaginal delivery in active cancer
DxTest of choicePelvic MRI (local staging); FDG-PET/CT (nodal/distant staging)
ScKey scoreFIGO 2018 Staging System
→When to referAny suspicious cervical lesion; Stage IB2 or higher for radiation oncology; Desire for fertility preservation
Cervical cancer management is stage-specific: early disease requires open radical surgery, while locally advanced disease requires cisplatin-based chemoradiotherapy and brachytherapy.
Cervical cancer is a malignant neoplasm of the uterine cervix, almost exclusively initiated by persistent high-risk human papillomavirus (hrHPV) integration [42, 61, 71]. It is the fourth most common malignancy in women globally and a leading cause of cancer death in low- and middle-income countries [9, 22, 72]. While organized screening and vaccination have reduced mortality in high-income nations, the disease remains a significant threat to younger populations and immunocompromised individuals [31, 36, 56].

Overview and Recommendations

Background

  • •Cervical cancer — primarily squamous cell carcinoma (70–80%) and adenocarcinoma (20–25%) — is the leading cause of gynecologic cancer death in sub-Saharan Africa and a major cause of morbidity in women aged 15–39.
  • •Persistent integration of hrHPV DNA into the host genome drives oncogenesis via the E6 and E7 oncoproteins, which facilitate the proteasomal degradation of and the inactivation of the protein (pRb), respectively.
  • •The global prevention strategy relies on the nonavalent HPV vaccine (targeting types 6, 11, 16, 18, 31, 33, 45, 52, and 58), which reduces the risk of invasive cancer by up to 88% when administered before age 17.
  • •Primary hrHPV DNA testing has superseded cytology as the preferred screening modality due to its superior sensitivity and high negative predictive value, allowing for safe 5-year screening intervals in low-risk populations.
  • •Gastric-type endocervical adenocarcinoma (GAS) represents a critical HPV-independent variant that is highly aggressive, often presents at advanced stages with peritoneal spread, and carries a significantly worse prognosis than usual-type adenocarcinoma.
  • •The FIGO 2018 staging revision marked a landmark shift by allowing MRI, CT, and PET/CT findings to upstage patients (specifically to Stage IIIC for nodal involvement), directly mandating a transition from surgical to radiation-based management.

Evaluation

  • •Suspect cervical cancer in any woman presenting with postcoital spotting, intermenstrual bleeding, or a malodorous, serosanguineous vaginal discharge.
  • •Perform a thorough speculum examination to visualize the cervix; look for friable, exophytic masses or endophytic 'barrel-shaped' enlargement that bleeds easily upon contact.
  • •Conduct a rectovaginal exam to assess for parametrial involvement (fixation or nodularity), which distinguishes Stage IIB disease and typically precludes primary radical surgery.
  • •Order a colposcopically directed biopsy for any suspicious lesion; taking at least 2–3 biopsies from the most abnormal areas increases the detection of high-grade lesions by 15–25% compared to a single biopsy.
  • •Utilize testing as a triage tool for HPV-positive women to identify those at high immediate risk for grade 3 (CIN3+).
  • •Perform a cold knife conization (CKC) rather than a loop electrosurgical excision procedure (LEEP) if adenocarcinoma in situ (AIS) or microinvasive disease is suspected, as CKC provides superior margin assessment and architectural preservation.
  • •Order a pelvic MRI as the gold standard for local tumor delineation, measuring tumor size (threshold of 2 cm for fertility-sparing) and assessing for bladder or rectal invasion.
  • •Obtain an FDG-PET/CT for all patients with Stage IB2 or higher to evaluate for pelvic and para-aortic lymphadenopathy, as PET/CT is more sensitive than conventional CT or MRI for nodal staging.
  • •Consider laparoscopic para-aortic lymphadenectomy if PET/CT is negative but pelvic nodes are positive, as surgical staging identifies occult metastasis in approximately 12–22% of these cases.
  • •Evaluate renal function (eGFR) and assess for hydronephrosis via imaging, as ureteral obstruction automatically classifies the disease as Stage IIIB.

Management

  • •Initiate management based on FIGO stage, prioritizing open radical for early-stage disease and concurrent chemoradiotherapy (CCRT) for locally advanced disease.
  • •Perform an open radical hysterectomy with pelvic lymphadenectomy for Stage IB1 and IB2 disease; avoid minimally invasive surgery (laparoscopic or robotic) as the LACC trial demonstrated a nearly four-fold increase in recurrence risk compared to open surgery.
  • •Offer simple hysterectomy for low-risk Stage IB1 lesions (≤2 cm, <10 mm stromal invasion, no LVSI) based on the SHAPE trial, which showed non-inferiority to radical surgery with better quality of life.
  • •Provide fertility-sparing options like radical trachelectomy or conization for patients with tumors <2 cm who desire future childbearing, but counsel on the increased risk of second-trimester miscarriage.
  • •Administer definitive CCRT for locally advanced disease (Stage IB3–IVA): weekly 40 mg/m² (maximum 70 mg) for 5–6 cycles concurrently with external beam radiation therapy (EBRT).
  • •Ensure the completion of image-guided adaptive (IGABT) following EBRT; omitting brachytherapy significantly compromises local control and overall survival.
  • •Avoid adjuvant systemic chemotherapy after completing definitive CCRT, as the OUTBACK trial showed no survival benefit and increased toxicity.
  • •Initiate first-line therapy for metastatic or recurrent disease (Stage IVB) with 200 mg every 3 weeks plus 175 mg/m² and 50 mg/m² (or AUC 5) ± 15 mg/kg.
  • •Restrict pembrolizumab use in the metastatic setting to patients whose tumors express PD-L1 with a Combined Positive Score (CPS) ≥1.
  • •Administer tisotumab vedotin 2.0 mg/kg (up to 200 mg) IV every 3 weeks as second-line therapy for patients who progress on or after platinum-based chemotherapy.
  • •Manage pregnancy-associated cervical cancer with a multidisciplinary team; neoadjuvant chemotherapy with and may be used after the first trimester to delay delivery until fetal maturity.
  • •Monitor for 3M syndrome (myocarditis, myositis, myasthenia gravis) in patients receiving immune checkpoint inhibitors, especially if they present with new-onset ptosis or dysarthria.
  • •Refer patients with recurrent disease confined to the pelvis for pelvic exenteration if they have previously received radiation and have no evidence of extrapelvic spread.
  • •Maintain intensive surveillance for the first 24 months post-treatment, as the majority of recurrences occur within this window; consider longitudinal monitoring of circulating HPV DNA (cHPV DNA) where available.

Board Review — High Yield

  • •LACC Trial — Landmark study showing open radical hysterectomy has superior disease-free survival compared to minimally invasive surgery (laparoscopic/robotic).
  • •FIGO Stage IIIC — New category in 2018 representing nodal involvement (IIIC1 pelvic, IIIC2 para-aortic) regardless of primary tumor size.
  • •p16INK4a — Immunohistochemical surrogate marker for high-risk HPV infection; used to confirm HSIL/CIN3.
  • •E6 and E7 — HPV oncoproteins that degrade p53 and inactivate pRb, respectively, leading to cell cycle escape.
  • •Gastric-type Adenocarcinoma — An HPV-independent, p16-negative subtype with a very poor prognosis and high rate of peritoneal spread.
  • •Sedlis Criteria — Clinical-pathological features (tumor size, LVSI, invasion depth) used to determine the need for adjuvant radiation after surgery.
  • •KEYNOTE-826 — Trial establishing the survival benefit of adding pembrolizumab to chemotherapy for metastatic PD-L1+ disease.
  • •Postcoital bleeding — The classic 'buzzword' clinical presentation for invasive cervical carcinoma.

Deep Dive — Evidence Details

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