Cervical Cancer

Introduction

Cervical cancer arises from the epithelium of the cervix and is, with very rare exceptions, caused by persistent infection with high-risk human papillomavirus (hrHPV) - making it one of the few cancers with a clearly identified, preventable infective cause.¹ This has driven the two major public health interventions covered in more detail elsewhere: HPV vaccination (primary prevention) and the national cervical screening programme (secondary prevention, detecting and treating pre-cancerous change before it becomes invasive - see the cervical screening article).

Globally, cervical cancer remains a major cause of cancer death in women, particularly where screening and vaccination programmes are less established; in the UK, incidence has fallen substantially since the introduction of screening and is expected to continue falling as vaccinated cohorts age into the screened population.

Aetiology and risk factors

HPV types 16 and 18 together account for the majority of cervical cancers; HPV integrates its DNA into cervical epithelial cells, and viral oncoproteins (E6 and E7) inactivate the tumour suppressor genes p53 and Rb respectively, disabling normal cell cycle control and allowing progressive dysplasia (CIN) to develop into invasive cancer if the infection persists rather than clears.²

• Persistent high-risk HPV infection (the necessary cause)
• Smoking - an independent risk factor, thought to impair local immune clearance of HPV and to have direct carcinogenic effects on cervical cells via tobacco metabolites concentrated in cervical mucus
• Immunosuppression (HIV, transplant recipients, long-term immunosuppressant use) - impairs viral clearance
• Early age at first intercourse and multiple sexual partners - increase cumulative HPV exposure
• Long-term combined oral contraceptive use (weak, likely modest, independent association)
• High parity
• Non-attendance at cervical screening

Histology

Clinical features

Early-stage cervical cancer is often asymptomatic and detected through screening, which is precisely the point of the programme - catching disease before symptoms develop.³ Symptomatic presentation usually reflects more established disease:

• Postcoital bleeding: the classic presenting symptom and should never be attributed to a benign cause (e.g. ectropion) without adequate assessment
• Intermenstrual bleeding
• Postmenopausal bleeding
• Offensive or blood-stained vaginal discharge
• Pelvic pain or dyspareunia: suggests more advanced local disease
• Symptoms of advanced disease: haematuria or urinary symptoms (bladder invasion), rectal bleeding or altered bowel habit (rectal invasion), leg swelling or pain (pelvic sidewall/lymphatic involvement), and flank pain (ureteric obstruction)

On speculum examination, an invasive tumour may appear as an irregular, friable, ulcerated or exophytic mass on the cervix that bleeds readily on contact - a very different appearance from the smooth, symmetrical red ring of a benign ectropion (see that article for the comparison).

Investigations

Colposcopy and biopsy

Direct visualisation with acetic acid/iodine application and biopsy of any suspicious area provides histological diagnosis - the essential first step whenever cervical cancer is suspected clinically, whether or not it was screening that raised concern.

Staging investigations

Once cancer is histologically confirmed, imaging defines local, nodal and distant spread to guide staging and treatment planning: MRI pelvis for local tumour size and parametrial/pelvic sidewall invasion, CT chest/abdomen/pelvis or PET-CT for nodal and distant metastatic disease, and examination under anaesthesia in some cases to assess local extent clinically.

Staging

Cervical cancer uses the FIGO staging system, which is based on clinical and radiological assessment of tumour size, depth of invasion, and spread to adjacent structures, lymph nodes and distant sites - distinct from purely surgical/pathological staging used in some other cancers.⁴

Management

Treatment is guided by stage, tumour size, and the woman's wish to preserve fertility, and is planned via a specialist gynaecological oncology multidisciplinary team.¹

Complications

• Ureteric obstruction and renal impairment from local tumour spread
• Fistula formation (vesicovaginal or rectovaginal) in advanced or treated disease
• Lymphoedema following pelvic lymphadenectomy or radiotherapy
• Premature ovarian insufficiency if radiotherapy or chemotherapy affects ovarian function (ovarian transposition can be performed before pelvic radiotherapy to preserve function where fertility/hormonal preservation matters)
• Vaginal stenosis after radiotherapy, affecting sexual function
• Psychological impact of a cancer diagnosis and, where relevant, loss of fertility

Prognosis

Prognosis is strongly dependent on stage at diagnosis: early-stage disease (confined to the cervix) has a very good prognosis with high five-year survival, while locally advanced and metastatic disease carry a substantially poorer outlook despite chemoradiotherapy. This stage-dependence is the central argument for both HPV vaccination and consistent cervical screening uptake, and for taking postcoital and postmenopausal bleeding seriously rather than assuming a benign cause without adequate assessment.