Cervical Cancer

Cervical cancer is a critical topic for UK medical finals due to its preventability and the robust national screening and vaccination programmes. It is the most common cancer in women under 35 in the UK. Over 99% of cases are linked to high-risk HPV infection, particularly types 16 and 18. The NHS Cervical Screening Programme invites women aged 25-64 for primary HPV screening, with cytology performed only if HPV is detected. This reflects a shift from cytology-first screening. The progression from HPV infection to invasive cancer is slow, typically 10-20 years, through stages of Cervical Intraepithelial Neoplasia (CIN). Squamous cell carcinoma accounts for 70-80% of cases, with adenocarcinoma making up the remainder. Early recognition of symptoms, particularly abnormal vaginal bleeding, is crucial for timely diagnosis and management.

High-risk HPV types (e.g., 16, 18) produce oncoproteins E6 and E7. E6 targets and degrades the tumour suppressor protein p53, while E7 inactivates the Retinoblastoma (Rb) protein. Both p53 and Rb are crucial for cell cycle control and apoptosis. Their inactivation leads to uncontrolled cell proliferation and genomic instability, driving malignant transformation. While most HPV infections are cleared by the immune system, persistent infection allows for viral DNA integration into the host genome, leading to a stepwise progression through Cervical Intraepithelial Neoplasia (CIN). CIN 1 involves the lower third of the epithelium, CIN 2 the lower two-thirds, and CIN 3 (carcinoma in situ) the full thickness. Invasion through the basement membrane defines invasive carcinoma. Understanding this progression is key to interpreting screening results and management.

The most important clinical presentation is **abnormal vaginal bleeding**: **post-coital bleeding (PCB)**, intermenstrual bleeding (IMB), or post-menopausal bleeding (PMB). These are red flag symptoms requiring urgent investigation. Other symptoms include unusual or offensive vaginal discharge (often 'blood-stained' or 'foul-smelling') and deep dyspareunia. Advanced disease can manifest with pelvic pain, weight loss, leg oedema (due to lymphatic obstruction), or obstructive uropathy (if ureters are compressed, leading to hydronephrosis and potential renal failure). On speculum examination, the cervix may appear normal in early stages, but later can show an exophytic mass, ulceration, or a firm, irregular 'barrel-shaped' cervix. Key risk factors include persistent high-risk HPV infection, smoking, early age of first intercourse, multiple sexual partners, and immunosuppression (e.g., HIV, transplant recipients). Always consider cervical cancer in women presenting with these symptoms, regardless of their last smear result.

Initial assessment involves a thorough history and **speculum examination** to visualise the cervix and identify any visible lesions. **Cervical screening** involves primary HPV testing; if positive, reflex cytology is performed. The gold standard for diagnosis is **colposcopy with directed biopsy**. During colposcopy, acetic acid and iodine are applied to highlight abnormal areas (acetowhite lesions, mosaicism, punctation) for targeted biopsy. For staging, **MRI Pelvis** is crucial for assessing local tumour extent, parametrial invasion, and nodal involvement. **CT Chest/Abdomen/Pelvis** is used to detect distant metastases. PET-CT may be used in advanced cases for comprehensive staging. Blood tests like FBC, U&Es, LFTs are for general health assessment and to detect complications (e.g., anaemia, renal impairment).

Management depends heavily on the FIGO stage and patient factors (e.g., fertility wishes). **Pre-cancerous lesions (CIN)** are typically managed with **Large Loop Excision of the Transformation Zone (LLETZ)** or cone biopsy. For **early invasive cancer (FIGO Stage IA)**, a cone biopsy or simple hysterectomy may be sufficient. For women desiring fertility preservation, a **radical trachelectomy** (removal of cervix and upper vagina, but not uterus) is an option. **Stage IB-IIA** usually requires **radical hysterectomy and pelvic lymphadenectomy**, or primary chemoradiotherapy. **Advanced stages (IIB-IV)** are primarily managed with **chemoradiotherapy** (cisplatin-based chemotherapy concurrent with external beam radiotherapy and brachytherapy). Palliative care focuses on symptom control, pain management, and addressing complications like fistulae or ureteric obstruction. Regular follow-up is essential post-treatment.