Cervical Cancer

An HPV-driven, largely preventable cancer — vaccination, screening, and treatment from LEEP to concurrent cisplatin-based chemoradiation

Key Points

• Virtually all cervical cancers are caused by persistent high-risk HPV infection, most commonly HPV-16 and HPV-18.
• Cervical cancer is potentially preventable through HPV vaccination (Gardasil 9) and Pap/HPV co-test screening.
• Squamous cell carcinoma is the most common histology (~70%); adenocarcinoma is increasing in incidence due to its lower Pap smear sensitivity.
• Early-stage disease (IA–IIA1) is treated with surgery (radical hysterectomy + pelvic lymph node dissection) or radiation with equivalent outcomes.
• Locally advanced disease (IIB–IVA) is treated with concurrent cisplatin + external beam radiation + brachytherapy — the interdigitation of surgery and radiation is determined by FIGO stage.
• Pembrolizumab + chemotherapy ± bevacizumab is now first-line standard for persistent, recurrent, or metastatic cervical cancer (PD-L1 CPS ≥1 — KEYNOTE-826).

Epidemiology & Incidence

Cervical cancer is the fourth most common cancer in women worldwide. In 2024, approximately 13,820 new cases and 4,360 deaths were projected in the US. The disparity between global burden and US incidence reflects the impact of widespread Pap smear screening and now HPV vaccination programs — in countries without screening, cervical cancer remains the second or third leading cause of cancer death in women. In the US, incidence has been declining steadily since the 1970s due to screening, though the rate of decline has slowed in recent years. Hispanic and Black women have higher incidence…

Genetic Predispositions & Risk Factors

Virtually all cervical cancers (>99%) are caused by persistent infection with one or more high-risk (oncogenic) HPV genotypes. HPV-16 and HPV-18 together account for ~70% of cervical cancers (HPV-16: ~55%; HPV-18: ~15%). HPV-16 is more commonly associated with squamous cell carcinoma; HPV-18 with adenocarcinoma. The mechanism: HPV E6 and E7 oncoproteins inactivate p53 and pRb tumor suppressors, respectively, leading to uncontrolled cell proliferation, genomic instability, and progression from CIN (cervical intraepithelial neoplasia) to invasive carcinoma. This progression typically takes…

Clinical Presentation

Early cervical cancer (stage I–IIA) is often asymptomatic and diagnosed through screening (abnormal Pap/HPV test → colposcopy → biopsy). When symptoms develop, they typically indicate locally invasive disease: • Abnormal vaginal bleeding — the most common symptom: intermenstrual bleeding, postcoital bleeding (characteristically contact bleeding after intercourse), or postmenopausal bleeding. Any postcoital bleeding in a non-pregnant patient mandates pelvic examination. • Vaginal discharge — watery, mucoid, or malodorous (from tumor necrosis); may be blood-tinged • Pelvic pain — indicates…

Staging Overview (FIGO 2018)

Cervical cancer is staged clinically using FIGO 2018 (which now allows imaging and pathologic findings to be incorporated, unlike older FIGO editions): Stage I: Confined to cervix uteri • IA1: Stromal invasion stage IA • IB2: >2 cm ≤4 cm • IB3: >4 cm (previously IIB in old staging) Stage II: Invades beyond uterus but not to pelvic wall or lower 1/3 vagina • IIA1: Upper 2/3 vagina, ≤4 cm • IIA2: Upper 2/3 vagina, >4 cm • IIB: Parametrial invasion Stage III: Extends to pelvic wall or lower 1/3 vagina, or causes hydronephrosis • IIIA: Lower 1/3 vagina, no pelvic wall extension • IIIB: Pelvic…

Stage I–IIA Treatment

Early-stage cervical cancer is potentially curable with either surgery or radiation — the choice depends on stage, fertility wishes, patient age, and comorbidities. Stage IA1 (microinvasive, no LVSI): Conization (LEEP or cold knife cone) with negative margins is curative for women desiring fertility preservation. Simple (extrafascial) hysterectomy for those not requiring fertility preservation. Stage IA2, IB1, IB2: Radical hysterectomy (type II or III — Querleu-Morrow classification) + bilateral pelvic lymph node dissection ± para-aortic node sampling. Minimally invasive radical hysterectomy…

Stage IIB–IVA and Metastatic Treatment

Locally Advanced Cervical Cancer (stage IIB–IVA): Concurrent cisplatin-based chemoradiation is the standard of care based on five landmark GOG/NCI trials. Cisplatin 40 mg/m² weekly (× 5–6 cycles) concurrently with external beam radiation therapy (45 Gy in 25 fractions to pelvis ± para-aortic fields extended field if N2 disease), followed by intracavitary brachytherapy boost (high-dose rate HDR or low-dose rate LDR) to point A (total 80–85 Gy EQD2 to tumor). Brachytherapy is an essential component — it provides the dose escalation to the primary tumor needed for local control and cannot be…