Cervical Cancer — HPV, Screening, Colposcopy & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Cervical cancer is a malignancy arising from the epithelium of the uterine cervix, almost exclusively caused by persistent infection with high-risk human papillomavirus (HPV). It is the fourth most common cancer in women globally, with 604,000 new cases and 342,000 deaths annually. The overwhelming majority (80%) of cases and deaths occur in low- and middle-income countries where HPV vaccination programmes and organised cervical screening have not yet been implemented. In high-income countries with effective screening programmes, cervical cancer incidence has fallen dramatically — by over 70% since the introduction of cytological screening. WHO's 2020 Global Strategy targets cervical cancer elimination — defined as an incidence below 4 per 100,000 women — through 90% HPV vaccination coverage, 70% screening coverage, and 90% access to treatment. The histological types are: squamous cell carcinoma (70-75% — arising at the squamocolumnar junction/transformation zone); adenocarcinoma (25-30% — from the endocervical glandular epithelium — less well detected by cytological screening); and rare types (small-cell neuroendocrine carcinoma — very aggressive).

Nearly all cervical cancers (99.7%) are caused by persistent infection with high-risk human papillomavirus (hrHPV) — a sexually transmitted virus. HPV types 16 and 18 account for approximately 70% of cervical cancers; types 31, 33, 45, 52, and 58 account for a further 15-20%. HPV is extremely common — approximately 80% of sexually active women will be infected at some point in their lifetime; the immune system clears most infections within 1-2 years. Persistent infection (lasting more than 1-2 years) with hrHPV leads to cervical intraepithelial neoplasia (CIN) — premalignant dysplasia of the squamous epithelium — which may progress to invasive cancer over 10-20 years if untreated. Risk factors for HPV infection and progression to cervical cancer: early age at first sexual intercourse (before 16); multiple sexual partners (both personal and partner's); other sexually transmitted infections (HSV-2, Chlamydia, HIV — all associated with persistent HPV); immunosuppression (HIV — 6-fold increased risk; organ transplant recipients); cigarette smoking (doubles the risk of cervical cancer even after controlling for HPV — cigarette carcinogens detected in cervical mucus); long-term combined oral contraceptive use (1.5-fold increased risk after 5+ years — returns to normal after cessation); and high parity.

Early-stage cervical cancer is often asymptomatic — detected by cervical screening (smear/HPV test) before clinical presentation. Symptoms of early invasive cervical cancer: intermenstrual bleeding (IMB — bleeding between periods); post-coital bleeding (PCB — the most classic and specific symptom — bleeding after sexual intercourse); postmenopausal bleeding (PMB); and abnormal vaginal discharge (watery, blood-stained, or offensive — from tumour breakdown). Advanced cervical cancer symptoms: pelvic pain (continuous, unrelated to menstrual cycle — from tumour invasion); loin pain or haematuria (from ureteric obstruction by tumour causing hydronephrosis); rectal symptoms (bleeding, altered bowel habit) from rectal invasion; leg oedema (lymphatic obstruction); weight loss and cachexia; and fistulae (vesicovaginal or rectovaginal fistulae from advanced disease or post-radiotherapy). Clinical signs on examination: visible tumour on the cervix (may be exophytic — 'cauliflower' growth — or endophytic — barrel-shaped, hardened cervix); contact bleeding on speculum examination; parametrial thickening or pelvic sidewall involvement on bimanual or rectal examination.

Cervical screening (primary prevention): hrHPV testing is now the primary screening test in England (replacing cytology as primary test since 2019) — samples are taken from the cervix by a healthcare professional using a speculum; if hrHPV is detected, the sample undergoes liquid-based cytology (LBC). Colposcopy referral: for any hrHPV-positive sample with abnormal cytology; repeated positive hrHPV (even with normal cytology); or clinical suspicion. Colposcopy: specialist examination of the cervix with magnification (colposcope) after application of acetic acid (highlights dysplastic areas as white — acetowhite — due to nuclear protein precipitation) and Lugol's iodine (dysplastic areas fail to stain — iodine-negative). Biopsy: colposcopy-directed punch biopsies confirm CIN grade (CIN1, CIN2, CIN3) or invasive cancer. CIN grading: CIN1 (mild dysplasia — often regresses spontaneously, 15-30% progress to CIN3 if untreated); CIN2 (moderate dysplasia — threshold for treatment); CIN3 (severe dysplasia/carcinoma in situ — treat). FIGO staging of invasive cervical cancer (based on clinical examination plus imaging): Stage I — confined to the cervix; Stage II — extends beyond cervix but not to pelvic sidewall; Stage III — extends to pelvic sidewall or lower third of vagina; Stage IV — invades bladder/rectum or distant metastases. MRI pelvis: best imaging for local staging, parametrial involvement, and lymph node assessment. CT chest/abdomen/pelvis: for distant metastases. PET-CT: for node mapping and planning radical treatment. Examination under anaesthesia (EUA) with cystoscopy/proctoscopy: for advanced disease staging.

CIN treatment (pre-invasive): LLETZ (large loop excision of the transformation zone) — outpatient, local anaesthetic, excises the entire transformation zone; allows histological confirmation of CIN grade and clearance; 90-95% cure rate for CIN2-3 in a single treatment. Cone biopsy (cold knife or laser): for endocervical or larger lesions. Ablative treatments (laser, cryotherapy): for well-visualised CIN1. Stage IA1 (microinvasive, invasion less than 3 mm): LLETZ or cone biopsy if margins clear and lymphovascular invasion absent (fertility-preserving); simple hysterectomy if fertility not required. Stage IA2-IB1 (tumour up to 4 cm): radical hysterectomy (Wertheim's hysterectomy — removes uterus, cervix, upper vagina, and parametria) with bilateral pelvic lymph node dissection (laparoscopic, robotic, or open); sentinel lymph node biopsy increasingly used. Note: LACC trial (2018) demonstrated open radical hysterectomy has superior oncological outcomes to minimally invasive approaches. Stage IB2-IIA (tumour 4-6 cm): concurrent chemoradiotherapy (CCRT) — cisplatin-based chemotherapy (40 mg/m2 weekly for 5 cycles) concurrent with external beam pelvic radiotherapy (45-50 Gy in 25 fractions) followed by brachytherapy (intracavitary radiotherapy — 5-7 Gy per fraction, 3-5 fractions). Stage IIB-IVA (locally advanced): CCRT is the primary treatment — 5-year overall survival 50-65% for Stage IIB; 30-35% for Stage IIIB. Neoadjuvant chemotherapy (NACT) before radical surgery is investigational. Recurrent/metastatic cervical cancer: pembrolizumab (anti-PD1 checkpoint inhibitor) is now first-line in combination with platinum-based chemotherapy plus bevacizumab for PD-L1+ recurrent or metastatic disease — KEYNOTE-826 trial: significantly improved overall survival (median 24 months vs 17 months). Tisotumab vedotin (antibody-drug conjugate) for platinum-refractory disease.

Fistulae (vesicovaginal or rectovaginal — from advanced tumour invasion or post-radiotherapy tissue necrosis; causing urinary or faecal incontinence through vaginal openings; require specialist urogynecological or colorectal surgical management). Lymphoedema (lower limb swelling from pelvic lymph node dissection or radiotherapy — chronic and progressive; managed with compression therapy). Ureteric obstruction (hydronephrosis from tumour compression — may cause irreversible renal failure requiring ureteric stenting or nephrostomy). Radiotherapy complications: radiation proctitis (rectal bleeding, urgency), radiation cystitis (haematuria, frequency), and vaginal stenosis (fibrosis causing severe dyspareunia — managed with vaginal dilators and topical oestrogen). Bladder dysfunction after radical surgery (urinary retention in 10-20% post-Wertheim hysterectomy from autonomic nerve damage — long-term clean intermittent self-catheterisation required). Recurrent disease (30-40% of locally advanced cases): managed with pelvic exenteration (selected cases) or palliative cisplatin-based chemotherapy with pembrolizumab.

HPV vaccination: the most transformative prevention strategy. Gardasil 9 (nine-valent HPV vaccine covering types 6, 11, 16, 18, 31, 33, 45, 52, 58) is highly immunogenic and provides over 97% protection against high-grade CIN caused by the included types when given before HPV exposure. In the UK, Gardasil 9 is offered to girls and boys aged 12-13 in schools. Catch-up vaccination is available to unvaccinated individuals up to age 25 in England, and up to age 45 in some settings. Real-world data from Scotland, Sweden, and Australia show dramatic reductions in CIN2+ and cervical cancer incidence in vaccinated cohorts — Scotland data show near-elimination of cervical cancer in women vaccinated at age 12-13 (approximately 87% reduction). Cervical screening attendance: all eligible women (25-64 in England) should attend cervical screening — primary HPV testing with cytology triage, every 5 years if HPV-negative; every 1-3 years if hrHPV-positive depending on colposcopy findings. Smoking cessation: reduces progression risk from HPV infection to CIN and invasive cancer. Immunosuppression management: HIV-positive women require annual cervical screening, starting at diagnosis regardless of age. Condom use reduces HPV transmission but does not eliminate it.

See a GP urgently (same or next working day) under the 2-week cancer pathway (2WW referral) for: post-coital bleeding (bleeding after intercourse) — particularly in sexually active women — regardless of cervical smear history; intermenstrual bleeding persisting beyond 3 months; postmenopausal bleeding (any bleeding after 12 months of no periods requires investigation to exclude gynaecological malignancy); or a visible suspicious lesion on the cervix seen by any clinician. Do not wait for a cervical smear result before seeing a doctor if you have symptoms — cervical cancer can develop between screening cycles, and symptomatic cancer must not be delayed by normal or pending screening results. Attend all cervical screening invitations when due — screening identifies precancerous changes (CIN) before they become cancerous, when they are completely curable. All people with a cervix aged 25-64 in England should attend cervical screening every 5 years (or more frequently if hrHPV is detected).