Cervical Cancer
Cervical cancer is a malignancy arising from the cervix, most commonly from the transformation zone, and is strongly linked to high-risk HPV infection.
This high-yield UKMLA guide, based on BGCS guidance and NICE CKS, covers risk factors, clinical features, diagnosis, and management.
Definition
Cervical cancer (invasive cervical carcinoma) is characterised by malignant cervical cells that have breached the basement membrane and invaded the underlying cervical stroma.
Cervical cancer is different from CINCervical intraepithelial neoplasia, a pre-cancerous (pre-invasive) condition, where abnormal (dysplastic) cells are present within the cervical epithelium that have NOT invaded through the basement membrane.
Types and Histology
Almost all cervical cancers originate from the transformation zone
Types of cervical cancer:
- Squamous cell carcinoma – most common (70-80% cases)
- Adenocarcinoma
- Other epithelial tumours are rare
The cervix is the lowest part of the uterus, composed of:
- Ectocervix: projects into the vagina, lined by squamous epithelium
- Endocervis: extends from the internal os to the external os, lined by columnar epithelium
Transformation zone: area where the squamous epithelium of the ectocervix meets the columnar epithelium of the endocervical canal (the squamocolumnar junction)
Causes and Risk Factors
Main cause: persistent infection of high-risk HPV
- High-risk HPV 16 and 18 account for 2/3 cases
- Other high-risk HPVs include 31, 33, 45, 52, 58
HPV is predominantly transmitted via sexual intercourse, risk factors include early age of sexual intercourse, multiple sexual partners / high-risk sexual partner, history of STI, and lack of use of barrier contraception.
~90% of incident HPV infections are short-lived and resolve spontaneously within 2 years. Only ~10% of all HPV infections become persistent, and increase the risk of cervical cancer.
Factors that increase the risk of progression to cervical cancer:
- Co-infection with other STIsSexually transmitted infections
- Smoking
- Immunosupression
- Use of COCP for >5 years
- Family history of cervical cancer
- High parity (>5 full-term births) and young age at first birth (<17 y/o)
Epideimology
Cervical cancer mainly affects sexually active women at 30-34 y/o
Cervical cancer is the 14th most common cancer in females in the UK
Clinical Features
Cervical cancer is typically asymptomatic at early stages.
Typical features:
- Abnormal vaginal bleeding – most common
- Intermenstrual bleeding
- Post-coital bleeding
- Post-menopausal bleeding
- Dyspareunia
- Abnormal vaginal discharge
- Abnormal cervix appearance (e.g. necrotic, friable, exophytic lesions)
Advanced disease can cause more severe features (due to spread into surrounding tissues / organs):
- Constitutional symptoms
- Lower limb oedema
- Pain (pelvic pain, bone pain, backpain, flank / loin pain) – often due to kidney / ureter complications
- Urinary and bowel issues (e.g. haematuria, urinary incontinence, urinary frequency, change in bowel habit)
Frequent sites for spread and metastasis:
- Pelvic and para-aortic lymph nodes
- Adjacent pelvic structures (e.g. vagina, ovaries, fallopian tubes, parametrium, bladder, rectum)
- Organs (e.g. lungs, bones, liver)
Investigation and Diagnosis
If cervical cancer is suspected clinically → suspected cancer pathway referral (to gynaecologist or colposcopist)
Choice of investigations:
- Confirm diagnosis with colposcopy and biopsy
Colposcopy is a diagnostic procedure performed after abnormal screening results (i.e. Pap smear). It involves real-time visual examination of the cervix using a colposcope (magnifying instrument with light source).
The purpose of colposcopy is to obtain a biopsy of abnormal tissue to allow histopathological diagnosis of cervical cancer.
To identify abnormal tissue of the cervix that requires biopsy, the following techniques are often used:
- Application of acetic acid: stains abnormal tissue white (acetowhitening)
- Application of iodine: stains normal tissue dark brown
- Post-diagnosis investigations
- MRI for local staging – all patients
- PET-CT for advanced cases
- Routine chest X-ray is recommended at pre-operative staging
- Sentinel lymph node biopsy to assess for nodal involvement
If the patient presents with clinically suspected cervical cancer, outside of the routine cervical screening (see the Cervical Screening article), do NOT perform a smear test for hrHPV testing and cytology; proceed straight to colposcopy.
Prevention
Advise on the following 3 points about preventing cervical cancer:
- Encourage women to participate in the cervical screening programme (for 25-64 y/o) – see the Cervical Screening (HPV) article
- Encourage to receive the HPV vaccine (Gardasil®9) at 12-13 y/o
- Advise sexually active individuals on the importance of using barrier contraceptive methods (e.g. condoms)
Management
Management largely depends on the clinical category, or more specifically the FIGO stage.
For exam and non-specialist level, it is appropriate to learn the management for the main clinical categories, and learn when and what fertility sparing options are appropriate.
| Clinical category | Corresponding FIGO stage | Standard management | Fertility sparing option (for those with incomplete family) |
|---|---|---|---|
| Microinvasive / very early disease | Stage IA1 | Primary treatment: excisional treatment with conisation (also known as cone biopsy) (options include LLETZLarge loop excision of the transformation zone, cold knife conisation, and laser conisation)
If the patient has completed her family → simple hysterectomy is an alternative option |
Excisional treatment with conisation (also known as cone biopsy) (options include LLETZLarge loop excision of the transformation zone, cold knife conisation, and laser conisation) |
| Early stage disease | Stage IA2, IB1, IB2 | Radical open abdominal hysterectomy + bilateral oophorectomy + pelvic lymph node dissection | Simple / radical trachelectomy (removal of the cervix, with the uterine body preserved), or
Conisation (also known as cone biopsy) (options include LLETZLarge loop excision of the transformation zone, cold knife conisation, and laser conisation) |
| Locally advanced disease | Stage IB3, IIA2, IIB, IIIA, IIIB, IVA | Chemoradiotherapy (external beam radiotherapy + bracytherapy + concurrent chemotherapy – usually cisplatin) | Rarely applicable |
| Distant metastasis | Stage IVB | Systemic chemotherapy (platinum + paclitaxel) | Not appropriate |
Full FIGO Staging
The updated 2018 FIGO classification is included for reference and completeness.
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Stage Group
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Sub-stage
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Definition
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|---|---|---|
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Stage I (Strictly confined to the cervix)
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IA1
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Microscopic disease; depth of stromal invasion < 3 mm
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IA2
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Microscopic disease; depth of stromal invasion ≥ 3 mm and < 5 mm
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IB1
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Invasive carcinoma ≥ 5 mm depth, but ≤ 2 cm in greatest dimension
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IB2
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Invasive carcinoma > 2 cm and ≤ 4 cm in greatest dimension
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IB3
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Invasive carcinoma > 4 cm in greatest dimension
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Stage II (Spread beyond cervix, but not to the pelvic wall or lower 1/3 of vagina)
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IIA1
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Involves the upper 2/3 of the vagina, tumor size ≤ 4 cm
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IIA2
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Involves the upper 2/3 of the vagina, tumor size > 4 cm
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IIB
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Tumour spreads into the parametrium (the connective tissue surrounding the uterus/cervix) but does not reach the pelvic sidewall
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Stage III (Spread to lower 1/3 of vagina, pelvic wall, or lymph nodes)
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IIIA
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Tumour involves the lower 1/3 of the vagina, with no extension to the pelvic wall
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IIIB
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Tumour extends to the pelvic sidewall AND/OR causes hydronephrosis (swelling of a kidney) or a non-functioning kidney
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IIIC1
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Metastasis to the pelvic lymph nodes (regardless of tumour size)
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IIIC2
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Metastasis to the para-aortic lymph nodes (regardless of tumour size)
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Stage IV (Spread beyond the true pelvis)
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IVA
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Tumour invades the mucosa of adjacent pelvic organs (the bladder or rectum)
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IVB
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Spread to distant organs (e.g., lungs, liver, bones)
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References
NICE CKS Cervical cancer and HPV