Invasive Cervical Cancer

Invasive cervical cancer is malignancy arising from the cervical epithelium. Most are squamous cell carcinoma, from the squamous epithelium of the ectocervix. Less commonly it is adenocarcinoma, from the glandular endocervical epithelium.

Persistent high-risk human papillomavirus infection is the essential causal factor in the great majority of cases (see cervical cancer screening). The transformation zone, where squamous and glandular epithelium meet, is the site of greatest oncogenic vulnerability.

Full screening and prophylactic vaccination programmes have produced a marked decline in incidence in populations with well established access. The condition remains a significant global cause of cancer mortality, particularly where screening and vaccination access is limited.

Pathophysiology and staging

• Progression from persistent high-risk human papillomavirus infection through cervical intraepithelial neoplasia to invasive malignancy typically takes many years to over a decade. This slow natural history is the rationale for structured, interval-based screening, which interrupts progression before invasive malignancy develops.
• Staging follows the International Federation of Gynecology and Obstetrics system. It incorporates tumour size and local extent, and the presence and extent of any regional or distant spread.
• Early-stage disease confined to the cervix is generally amenable to surgery. More advanced, locally extensive disease (involving the parametrium, pelvic sidewall, or adjacent pelvic organs) generally needs primary chemoradiotherapy rather than surgery.
• The characteristic pattern of progression is direct local extension to adjacent pelvic structures and lymphatic spread to pelvic and, in more advanced disease, para-aortic lymph nodes. Distant haematogenous metastasis occurs predominantly in more advanced or recurrent disease.

• Early-stage cervical cancer is frequently asymptomatic. It is identified through structured screening before symptoms develop, which shows the value of screening in detecting disease at an earlier, more favourable and readily treatable stage.
• Abnormal vaginal bleeding is the commonest symptomatic presentation once disease becomes clinically apparent. Postcoital bleeding is a classic presenting symptom that warrants prompt clinical attention. Intermenstrual bleeding and, in postmenopausal women, postmenopausal bleeding also occur (see vaginal bleeding).
• Abnormal vaginal discharge, sometimes blood-stained or malodorous, is a further presenting feature.
• More advanced disease can cause pelvic pain. Involvement of adjacent structures causes bladder or bowel symptoms (including haematuria or altered bowel habit).
• Any woman with postcoital bleeding needs prompt assessment, including direct visualisation of the cervix, regardless of recent screening history. This symptom may indicate cervical pathology needing targeted evaluation, and screening history alone is not reassuring.

• Direct visualisation of the cervix, with colposcopic assessment and biopsy of any visible, abnormal lesion, gives the definitive histological diagnosis. It is the essential initial approach for any woman with symptoms or examination findings suggestive of invasive cervical malignancy.
• Staging assessment is essential and directly informs treatment planning. It incorporates clinical examination under anaesthesia (assessing local extent of disease) and magnetic resonance imaging of the pelvis (detailed assessment of local tumour extent and any parametrial or adjacent organ involvement).
• For more advanced disease, add computed tomography or positron emission tomography combined with computed tomography to assess regional nodal and distant metastatic spread.
• Examination under anaesthesia, with cystoscopy and, where relevant, proctoscopy, may be performed to assess bladder or bowel involvement in more locally advanced disease. This contributes to clinical staging alongside the imaging findings.

• Early-stage disease confined to the cervix is generally managed surgically. The extent of surgery is individualised to tumour characteristics and stage: simple hysterectomy for the very earliest, smallest lesions, and radical hysterectomy with pelvic lymphadenectomy for somewhat larger, though still early-stage, disease.
• Fertility-sparing surgery, including radical trachelectomy (removal of the cervix with preservation of the uterine body), is an important option for carefully selected, appropriately staged younger women who wish to preserve fertility. It is delivered through specialist gynaecological oncology services with expertise in this approach.
• More advanced, locally extensive disease is generally managed with primary chemoradiotherapy. This is the standard treatment for disease not amenable to primary surgery because of its local extent. It comprises external beam radiotherapy with concurrent platinum-based chemotherapy, plus brachytherapy (internal radiotherapy delivered directly to the cervix and adjacent structures).
• Metastatic or recurrent disease is managed with systemic chemotherapy and, increasingly, targeted and immunotherapy approaches in selected patients. The goals are disease control, symptom palliation, and quality of life, with integrated palliative care involvement addressing the broader needs of this population.
• Manage the significant longer-term consequences of treatment as an integral part of long-term care. This includes treatment-related menopause in younger women (see primary ovarian insufficiency and menopause), relevant to ovarian failure from pelvic radiotherapy or surgical oophorectomy.
• Also manage lymphoedema, sexual dysfunction, and bowel or bladder dysfunction following radical surgery or radiotherapy.
• Provide structured, long-term follow-up. Continue to emphasise primary prevention through human papillomavirus vaccination and screening programme participation, which reduce the population burden of this largely preventable malignancy.