Cervical Cancer: Causes, Symptoms, Diagnosis and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Cervical cancer is the 4th most common cancer in women worldwide, with approximately 660,000 new cases and 350,000 deaths annually (WHO 2020). Over 99% of cases are causally linked to persistent infection with high-risk human papillomavirus (hrHPV), making cervical cancer one of the most preventable cancers through vaccination and screening. Histologically, squamous cell carcinoma (approximately 70%) and adenocarcinoma (approximately 25%) are the dominant subtypes. Incidence has declined dramatically in countries with organized Pap smear screening programs — by over 80% in some high-income countries. The disease disproportionately affects women in low- and middle-income countries (LMICs), where approximately 90% of deaths occur due to limited access to vaccination, screening, and treatment. Australia, the UK, and Nordic countries with high HPV vaccination coverage are on track for cervical cancer elimination (defined as fewer than 4 per 100,000 incidence) within this generation.

Persistent infection with high-risk HPV is the necessary etiological cause of virtually all cervical cancers. HPV 16 and 18 together account for approximately 70% of cervical squamous cell carcinomas; HPV 18 disproportionately causes adenocarcinomas. Other oncogenic high-risk types include HPV 31, 33, 45, 52, and 58. Risk factors that promote HPV persistence and malignant progression: early age of first sexual intercourse, multiple lifetime sexual partners, HIV infection and immunosuppression (10-fold increased risk), smoking (approximately doubles the risk), long-term oral contraceptive use (over 5 years), high parity (3 or more full-term pregnancies), and absence of Pap smear screening. Most HPV infections clear spontaneously within 2 years; malignant transformation requires years to decades and integration of HPV DNA into the host genome with overexpression of E6 and E7 oncoproteins that inactivate p53 and pRb.

Early-stage cervical cancer (CIN and FIGO stage IA) is asymptomatic and detected exclusively by Pap smear or colposcopic examination — this is why screening saves lives. The most common symptom of invasive cervical cancer is abnormal vaginal bleeding: post-coital bleeding, intermenstrual bleeding, or postmenopausal bleeding in women who have gone through menopause. Malodorous vaginal discharge, which may be blood-tinged, is another common presenting feature. Pelvic or lower back pain indicates parametrial or pelvic sidewall involvement. Advanced disease produces renal failure from bilateral ureteral obstruction (hydronephrosis), lower extremity edema from pelvic lymphatic or venous obstruction, vesicovaginal or rectovaginal fistulae (abnormal connections causing urinary or fecal leakage into the vagina), and progressive cachexia.

Cervical cytology (Pap smear) and HPV co-testing for population screening; colposcopy with directed biopsy of acetowhite or mosaic epithelium for abnormal screening results. Cervical punch or cone biopsy (LLETZ/LEEP) for histological diagnosis. FIGO 2018 clinical staging integrates imaging: MRI of the pelvis for local tumor extent, parametrial invasion, vaginal extension, and lymph node status; PET-CT for nodal and distant metastatic staging. Cystoscopy and sigmoidoscopy for stage IVA disease. HPV genotyping (16/18 positivity), p16 immunohistochemistry (surrogate for hrHPV integration), and PD-L1 Combined Positive Score (CPS) expression guide treatment decisions particularly for metastatic disease. Tumor markers: SCC antigen (squamous) and CA-125 (adenocarcinoma) for monitoring.

CIN 2-3 (high-grade precancer): LEEP (loop electrosurgical excision procedure) or cold knife cone biopsy — highly curative. Stage IA1 (microinvasive): simple hysterectomy or cone biopsy for fertility preservation. Stage IA2-IB1: radical hysterectomy with bilateral pelvic lymphadenectomy (Wertheim hysterectomy) — equivalent cure rates to chemoradiation for early-stage disease, with the advantage of preserving ovarian function in premenopausal women. Stage IB2-IVA: concurrent chemoradiation — external beam radiotherapy (45-50 Gy in 25 fractions) plus weekly cisplatin 40 mg/m2 followed by intracavitary brachytherapy boost (high-dose-rate brachytherapy) is standard of care and achieves 70-85% cure for stage IB2-IIA. Metastatic/recurrent disease: pembrolizumab plus carboplatin or cisplatin plus paclitaxel, with or without bevacizumab (KEYNOTE-826) — first-line standard. Tisotumab vedotin (antibody-drug conjugate targeting tissue factor) for third-line metastatic disease.

Prognosis for cervical cancer is strongly determined by FIGO stage at diagnosis. Stage IA1-IA2 (microinvasive): 5-year overall survival exceeds 97-99% after appropriate surgical or ablative treatment. Stage IB1 (tumor less than 2 cm): 5-year OS approximately 90-95% with radical hysterectomy or chemoradiation. Stage IB2-IIB: 5-year OS approximately 70-85% with concurrent chemoradiation plus intracavitary brachytherapy. Stage III: 5-year OS approximately 40-55% with chemoradiation; para-aortic node-positive disease (IIIC2) has 5-year OS approximately 30-40%. Stage IVA: 5-year OS approximately 15-20% with chemoradiation; Stage IVB (distant metastases): median OS approximately 18-24 months with pembrolizumab-based regimens (KEYNOTE-826 trial). Without treatment, invasive cervical cancer progresses to locally advanced and metastatic stages within 1-3 years of symptom onset, with near-universal mortality. Complete HPV vaccination programs in countries such as Australia project cervical cancer elimination (incidence less than 4 per 100,000) within this generation. Key prognostic factors include FIGO stage, lymph node status, tumor size, parametrial invasion, histological subtype (adenocarcinoma may have slightly worse prognosis than squamous cell), and PD-L1 expression in metastatic disease. After primary treatment, 80% of recurrences occur within 2 years; surveillance protocol includes gynecological examination every 3-6 months for 2 years, then annually for years 3-5, with CT or PET-CT for recurrence evaluation. Patients treated with radical radiotherapy require long-term monitoring for radiation-related late effects including bowel, bladder, and sexual dysfunction.

HPV vaccination is the most powerful primary prevention strategy: the 9-valent vaccine (Gardasil 9) prevents HPV types 16, 18, 31, 33, 45, 52, and 58, responsible for approximately 90% of cervical cancers. ACIP (US), NICE (UK), and WHO all recommend vaccination at ages 9-14 (before sexual debut) for maximum efficacy, with catch-up vaccination to age 26 (and shared clinical decision-making to age 45). Secondary prevention through organized cervical screening: co-testing (Pap + HPV every 5 years, ages 25-65) or primary HPV testing alone (every 5 years) enables detection and treatment of pre-invasive CIN before malignant transformation. LEEP treatment of CIN 2-3 is 95% effective. Smoking cessation reduces cervical cancer risk. Safe sex practices and reducing number of sexual partners reduce HPV transmission risk.

See a doctor promptly for: any post-coital bleeding (vaginal bleeding after sexual intercourse) — this is a cardinal symptom requiring urgent colposcopy; intermenstrual bleeding that is new or recurrent; postmenopausal vaginal bleeding (any bleeding after 12 months of amenopause requires investigation); persistent malodorous vaginal discharge; or pelvic pain that is new, progressive, and unexplained. All sexually active women should attend regular cervical screening as recommended by their country's program — typically starting at age 21-25. Women living with HIV or other immunosuppression should be screened more frequently. Women who have not received HPV vaccination should consider catch-up vaccination up to age 45 with shared clinical decision-making. Missed screening appointments are the leading reason cervical cancer is diagnosed at advanced stages.