Cervical cancer Flashcards
Define
Malignancy of the cervical mucosa
Cause
Persistent HPV infection
HPV is responsible for > 99% of cases
HPV is a small, double-stranded DNA virus
There are > 100 different types
- Strains 6 and 11 are considered low risk, causing benign warts
- Strains 16, 18, 31, 33 and 45= HIGH RISK – these cause CERVICAL CANCER
- 16 and 18 are the most aggressive- responsible for 80% of cervical cancer
- 18 and 485 have a high risk of recurrence
HPV infection is spread during sexual intercourse
Infection is very common following the onset of sexual activity and a minority develop persistent genital infection which predisposes them to premalignant and malignant change
Risk factors
Major: HPV infection
Minor:
- Smoking: Reduces the efficiency of HPV being cleared by the immune system and increases the risk of persistent infection
- Early first intercourse
- Many sexual partners
- Immunocompromised e.g. HIV patients, transplant recipients
- Age group (Those around the mid-life, Frequent in 35-44 years)
- High parity (>5)
- COCP
Pathophysiology
The tubular cervix is composed of stromal tissue covered by:
- Squamous epithelium- in the vagina (ectocervix)
- Columnar epithelium- in the cervical canal (endocervix).
The meeting of the squamous and columnar epithelium is called the SQUAMOCOLUMNAR JUNCTION. This is usually on the ectocervix
The position of the SCJ varies throughout life:
- In CHILDREN- lies at the external cervical os
- At PUBERTY- extends outwards onto the ectocervix as the cervix enlarges
- In ADULTS- returns to the external cervical os through the process metaplasia
This is the physiological transformation of columnar to squamous epithelium.
- The TRANSFORMATION ZONE is the area between the original SCJ and the current SCJ where the epithelium changes from columnar to squamous over time.
- When HPV infection persists, it triggers an oncogenic process in the transformation zone, leading to metaplasia.
- Integration of HPV DNA into the basal epithelial cells leads to immortalisation and rapid cellular turnover
- Disordered immaturity within the epithelium is called cervical intraepithelial neoplasia (CIN). It is an intraepithelial condition. This is a pre-malignant disease of the cervix.
REMEMBER: cancer is diagnosed when it invades through the basement membrane
Classified as CIN 1, CIN2, CIN 3
Low-grade (CIN 1)
High-grade (CIN 2-3)
- 70% of cervical cancers are squamous cell carcinomas
- Adenocarcinomas make up the remainder
- The tumour can grow through the cervix into the parametria, bladder, vagina and rectum
Sites of metastasis:
- Pelvic (iliac and obturator) lymph nodes
- Para-aortic nodes
- Liver
- Lungs
Sings and symptoms
ASYMPTOMATIC- if small volume microscopic disease
- Abnormal bleeding
- Post-coital bleeding
- Intermenstrual bleeding
- Postmenopausal bleeding
- Mucoid or purulent vaginal discharge
- Dyspareunia
- Cervical mass that bleeds on contact
- PV discharge (offensive or bloodstained)
Hardness or fixity of tissues- in advanced disease
Symptoms of advanced disease
- Pain- pelvic/ back
- Incontinence (vesicovaginal fistulae)
- Anaemia
- Renal failure
- Bladder, renal or bowel obstruction
- Bone pain
Investigations
Vaginal examination (BIMANUAL) + Speculum
- May see cervical mass that bleeds on contact
- Biopsy should be taken in outpatient setting
- NOTE: endophytic tumours are less clinically revealing than exophytic
Cervical cytology
- Liquid-based cytology: a small brush is used to sample cells from the transformation zone. The brush head is placed in a fixative. The cells are examined microscopically
- Abnormal cervical cytology shows squamous cells at different stages of maturity (dyskaryosis).
Cervical cytology can be classified as:
- Normal
- Low grade- minor cytological abnormalities showing mild dyskaryosis and/or borderline change
- High grade- moderate and severe dyskaryosis.
- Cervical cytology triages patients to the colposcopy clinic for further assessment
- 95% of women have normal cervical cytology
Colposcopy (+ biopsy)
Inspected with binocular microscope. acetic acid stain 5% stains
- white abnormal cells (high nuclear density). Iodine also helps this - high glycogen cells
- This is examination of the magnified cervix using a light source
- The woman is in a semi-lithotomy position
- A speculum is placed in the vagina and the cervix is examined with a light source
- Application of acetic acid and iodine solution highlight the ABNORMAL areas of the cervix
Acetic acid- areas of increased cell turnover (including CIN) appear WHITE
Iodine- areas of CIN lack intracytoplasmic glycogen and therefore FAIL to stain brown with iodine
Key diagnostic criteria:
- Abnormal vascularity
- White change with acetic acid
- Obvious exophytic lesions
CIN can also be classified as low or high-grade based on colposcopy
- Low-grade: subsequent colposcopy and cytology in 6 months
- High-grade: treated in clinic on the same visit (‘see and treat’)
Biopsies may be taken if unsure
- Biopsy confirms diagnosis histologically
- Biopsy- confirm malignancy and assess the tumour type
MRI of abdomen and pelvis- allows assessment of spread
CXR- check for lung metastases
Rectovaginal examination under anaesthetic- may be necessary to assess tumour size, fixity and vaginal involvement
Cystoscopy- may be used to check for bladder involvement
- Small mobile tumours favour SURGERY
- Large fixed tumours favour use of RADIOTHERAPY
NOTE: staging is largely based on clinical findings rather than surgery and pathology
Management
Stage Ia1 (microinvasive): E7 = RbP (retinoblastoma protein)
- Conservative
- LLETZ, cone biopsy (follows smear pathway) -Loop electrical excision procedure-
Stage Ia2 to IIa (early stage):
- Fertility-sparing -> Radical trachelectomy (remove cervix) + bilateral pelvic node dissection
- Tumours ≤4cm -> Radical hysterectomy + bilateral pelvic node dissection (Wertheim’s)
- Tumours ≥4cm -> Chemoradiation
Stage IIb to IVa (locally advanced disease):
- Chemoradiation
Stage IVb (metastatic disease):
- Combination chemotherapy
- Single agent therapy and palliative care
- Radiotherapy (2 types; see below) ± chemotherapy (cisplatin-based therapy):
- External beam radiotherapy (10 minutes of delivery, completed over 4 weeks)
- Internal radiotherapy (brachytherapy; rods of radioactive selenium is inserted into the affected area)
Complications
Surgical risk (Wertheim’s hysterectomy)
- Bladder dysfunction (atony) à common, may require intermittent self-catheterisation
- Sexual dysfunction (due to vaginal shortening)
- Lymphoedema (due to pelvic lymph node removal) à leg elevation, good skin care and massage
Radiotherapy (more often used than chemotherapy, which is used for later stage cancer):
- Lethargy / fatigue Urgency
- Skin erythema (external beam radiotherapy) Dyspareunia / vaginal stenosis
- Infertility Diarrhoea / malabsorption
- Dysuria Incontinence
Prognosis
Most recurrence occurs within 2 years
Tumour may spread locally to the lymphatics (pelvic, para-aortic, supraclavicular), haematogenously, transcelomically
5-year survival rate dependent stage of disease at diagnosis:
Locally – Stage I (92%)
Regionally – Stage II and III (56%)
Distant – Stage IV (17%)
Cervical cancer survivors at risk of developing HPV-associated primary cancer but risk is low
