Gynae Cancer Flashcards
What is the cervix?
The cervix is an anatomical region which facilitates the passage of sperm into the uterine cavity and maintains sterility of the upper female reproductive tract.
The cervix is composed of 2 regions. What are they?
- Endocervical canal - ends t a narrowing called the internal os which marks the beginning of the uterine cavity
- Ectocervix - distal part of cervix that projects into vagina
What epithelium lines the endocervical canal?
Mucus-secreting simple columnar epithelium
What epithelium lines the ectocervix?
Stratified squamous non-keratinised epithelium which is resistant to the low pH of the vagina
What marks the tranition from the ectocervix to the endocervical canal?
External os
What is the squamocolumnar junction (SCJ)?
The location where the squamous epithelium of the ectocervix and columnar epithelium of the endocervix meet
What happens when the columnar epithelium of the endocervix is exposed to the acidic environment in the vagina?
it undergoes squamous metaplasia
What happens during squamous metaplasia?
During this process, the original SCJ everts from its original position onto the ectocervix; the area between the original SCJ and the new SCJ is known as the transformation zone.
What is the most common cause of cervical cancer?
infection with human papillomavirus (HPV)
Primary transmission of HPV?
Sexually transmitted infection
There are over 100 strains of HPV. What are the 2 most important ones?
Type 16 and type 18 - they are responsible for around 70% of cervical cancers and also the strains targeted with the HPV vaccine
What strains of HPV are targeted by the HPV vaccine?
Type 16 and 18
Pathogenesis/carcinogenesis behind cervical cancer?
- Microtrauma to the epithelial cells of the transformation zone provides HPV with access to basal keratinocytes.
- HPV infects these cells with its surface proteins and uses its E6 and E7 oncoproteins to inhibit the tumour suppressors p53 and pRb, resulting in uncontrolled cellular proliferation.
- The ensuing accumulation of mutations results in pre-malignant cellular abnormalities, named cervical intraepithelial neoplasia (CIN).
- Eventually, CIN can progress to invasive carcinomas
What is the most common type of cervical cancer?
Squamous cell carcinoma (80%) of the epithelial lining of the ectocervix.
Where are cervical squamous cell carcinomas found?
ectocervix
What is the 2nd most common type of cervical cancer?
Adenocarcinomas (of the glands within the lining of the cervix)
Give some other, rarer, routes of transmission of HPV
- Contact with contaminated surfaces or objects
- Oro-genital transmission
- Perinatal vertical transmission
- Autoinoculation
What are P53 and pRb?
Tumour supressor genes
How does HPV inhibit tumour suppressor genes?
HPV produces two proteins (E6 and E7) that inhibit these tumour suppressor genes
Therefore, HPV promotes the development of cancer by inhibiting tumour suppressor genes.
Which protein produced by HPV inhibits p53?
E6 protein
Which protein produced by HPV inhibits pRb?
E7
What are some risk factors of cervical cancer?
The greatest risk factor for developing cervical cancer is HPV infection. Other factors include:
- Smoking
- Inadequate cervical screening
- High parity
- Oral contraceptive use
- Lower socioeconomic status
- Co-infection with other sexually transmitted infections, such as HIV, herpes simplex and chlamydia
- Previous cancers of the vagina, vulva, kidneys and urinary tract
Risk factors for CATCHING HPV:
- Early sexual activity
- Increased number of sexual partners
- Sexual partners who have had more partners
- Not using condoms
What should be asked about in a patient’s history when assessing for cervical cancer?
- Symptoms e.g. bleeding
- Attendance to smears
- Sexual history: number of sexual partners, type of sexual intercourse, use of barrier contraception, risk of other sexually transmitted infections
- Family history
- Smoking/OCP use
- Obstetric history: parity and gravidity
- HPV infection & vaccination history
Majority of HPV infections are ASYMPTOMATIC.
Give some symptoms seen in cervical cancer/HPV infection:
- Abnormal vaginal bleeding (intermenstrual, postcoital, postmenopausal)
- Vaginal discharge (blood-stained, mucoid or purulent)
- Pelvic pain
- Dyspareunia
N.B. These symptoms are non-specific, and in most cases, not caused by cervical cancer. The next step is to examine the cervix with a speculum. During examination, swabs can be taken to exclude infection.
What is dyspareunia?
Pain or discomfort with sex
What is the next stage in assessment in a patient presenting with potential cervical cancer symptoms?
The next step is to examine the cervix with a speculum. During examination, swabs can be taken to exclude infection.
If there is an abnormal appearance of the cervix suggestive of cancer during speculum, what is the next step?
An urgent cancer referral for colposcopy should be made to assess further.
During a speculum examination, what appearances may suggest cervical cancer?
Ulceration
Inflammation
Bleeding
Visible tumour
What happens if there is an abnormal appearance of the cervix suggestive of cancer during speculum exam?
an urgent cancer referral for colposcopy should be made to assess further.
Give some differentials for suspected cervical cancer
- Cervicitis
- Ectropion
- Endometrial cancer
What is cervicitis?
Inflamed, friable cervix prone to bleeding
Commonly caused by chlamydia trachomatis
What is cervicitis commonly caused by?
Chlamydia trachomatis
What is ectropion?
A benign condition involving the presence of columnar epithelium on the outside of the cervix
Prone to bleeding/infection although if asymptomatic then no treatment required
Could cauterise if wished
How are most cases of cervical cancer diagnosed?
Through cervical screening
What does cervical screening involve?
It involves a cervical smear test, performed by a qualified person, often a practice nurse
What is a smear test?
The test consists of a speculum examination and collection of cells from the cervix using a small brush. The cells are deposited from the brush into a preservation fluid. This fluid is transported to a lab where the cells are examined under a microscope for precancerous changes (dyskaryosis).
What is dyskaryosis?
Dyskaryosis relates to pre-cancerous cell changes,
What are cervical smear samples initially tested for before the cells are examined?
High risk HPV
If the HPV test is negative (the person does not have HPV) when testing the cervical smear sample, what happens?
the smear is considered NEGATIVE and the woman is returned to the routine screening program.
Who is invited to the cervical screening program? How often?
women (and transgender men that still have a cervix):
- Every three years aged 25 – 49
- Every five years aged 50 – 64
Some notable exceptions to the cervical screening program:
- Women with HIV are screened annually
- Women over 65 may request a smear if they have not had one since aged 50
- Women with previous CIN may require additional tests (e.g. test of cure after treatment)
- Certain groups of immunocompromised women may have additional screening (e.g. women on dialysis, cytotoxic drugs or undergoing an organ transplant)
- Pregnant women due a routine smear should wait until 12 weeks post-partum
If the HPV test is positive (the person does have HPV) when testing the cervical smear sample, what happens?
The cells are examined
Potential cytology results during cervical screening:
- Inadequate
- Normal
- Borderline changes
- Low-grade dyskaryosis
- High-grade dyskaryosis (moderate)
- High-grade dyskaryosis (severe)
- Possible invasive squamous cell carcinoma
- Possible glandular neoplasia
N.B. Infections such as bacterial vaginosis, candidiasis and trichomoniasis may be identified and reported on the smear result.
What happens if the cervical smear sample is inadequate?
repeat the smear after at least three months
What happens if the cervical smear sample is HPV negative?
continue routine screening
What happens if the cervical smear sample is HPV positive with normal cytology?
repeat the HPV test after 12 months
What happens if the cervical smear sample is HPV positive with abnormal cytology?
Refer for colposcopy
Who should fast track colposcopy be offered to?
Fast-track colposcopy should be offered to women with visible suspicion of cervical cancer or persistent unexplained cervical symptoms.
A gynaecology 2-week wait referral should be made in the following cases:
- Postmenopausal women with unexplained vaginal bleeding
- Premenopausal women with persistent intermenstrual bleeding and negative pelvic exam
- Women with clinical features suggesting cervical cancer if they have not been screened, or if the bleeding persists beyond 3 months
Consider referring premenopausal women to gynaecology or genitourinary services if they have persistent abnormal bleeding and the presence of polyps, ectropion, cervicitis or warts.
What is cervical intraepithelial neoplasia (CIN) ?
A grading system for the level of dysplasia (premalignant change) in the cells of the cervix.
When is CIN diagnosed?
CIN is diagnosed at colposcopy (not with cervical screening)
What are the CIN grades?
CIN I: mild dysplasia, affecting 1/3 the thickness of the epithelial layer, likely to return to normal without treatment
CIN II: moderate dysplasia, affecting 2/3 the thickness of the epithelial layer, likely to progress to cancer if untreated
CIN III: severe dysplasia, very likely to progress to cancer if untreated (sometimes called cervical carcinoma in situ)
What is a colposcopy?
A specialist performs colposcopy. It involves inserting a speculum and using equipment (a colposcope) to magnify the cervix. This allows the epithelial lining of the cervix to be examined in detail.
Can using stains to differentiate abnormal areas.
A punch biopsy or large loop excision of the transformational zone can be performed during the colposcopy procedure to get a tissue sample.
What stains can be used during colposcopy to differentiate abnormal areas?
acetic acid and iodine solution
What is the effect of acetic acid on abnormal cells during colposcopy?
Acetic acid causes abnormal cells to appear white. This appearance is described as acetowhite.
This occurs in cells with an increased nuclear to cytoplasmic ratio (more nuclear material), such as cervical intraepithelial neoplasia and cervical cancer cells.
What is Schiller’s iodine test?
Used during colposcopy
Schiller’s iodine test involves using an iodine solution to stain the cells of the cervix. Iodine will stain healthy cells a brown colour. Abnormal areas will not stain.
What colour will abnormal cells turn when using acetic acid during colposcopy?
White
What colour will abnormal cells turn when using iodine during colposcopy?
Abnormal areas will not stain.
What colour will normal cells turn when using iodine during colposcopy?
Brown
What type of biopsy can be performe during colposcopy to get a tissue sample?
A punch biopsy or large loop excision of the transformational zone
What is a Large Loop Excision of the Transformation Zone (LLETZ)?
Is also called a loop biopsy. It can be performed with a local anaesthetic during a colposcopy procedure.
It involves using a loop of wire with electrical current (diathermy) to remove abnormal epithelial tissue on the cervix. The electrical current cauterises the tissue and stops bleeding.
Complications of LLETZ?
Bleeding and abnormal discharge can occur for several weeks following a LLETZ procedure. This varies between women.
Intercourse and tampon use should be avoided after the procedure to reduce the risk of infection.
Depending on the depth of the tissue removed from the cervix, the procedure may increase the risk of preterm labour.
What is a cone biopsy?
A cone biopsy is a treatment for cervical intraepithelial neoplasia (CIN) and very early-stage cervical cancer.
Involves general anaesthetic.
The surgeon removes a cone-shaped piece of the cervix using a scalpel. This sample is sent for histology to assess for malignancy.
What are the main risks of cone biopsy?
Pain
Bleeding
Infection
Scar formation with stenosis of the cervix
Increased risk of miscarriage and premature labour
What staging system is used to stage cervical cancer?
International Federation of Gynaecology and Obstetrics (FIGO)
FIGO staging for cervical cancer:
Stage 1: Confined to the cervix
Stage 2: Invades the uterus or upper 2/3 of the vagina
Stage 3: Invades the pelvic wall or lower 1/3 of the vagina
Stage 4: Invades the bladder, rectum or beyond the pelvis
The treatment for cervical cancer depends on the stage of the cancer, and also whether the woman wants to retain fertility.
What is the management of CIN?
CIN-1 is not routinely offered treatment and should be observed
CIN-2/CIN-3: excision or ablation may be considered (e.g. LLETZ or cone biopsy)
What is management of cervical cancer stage 1B-2A (early stage disease)?
Radical hysterectomy and removal of local lymph nodes (lymphadenectomy) with/without chemotherapy and radiotherapy –> NO aim to spare fertility
Radical trachelectomy can be done for slightly more advanced, yet still early-stage cancers –> the aim is to spare fertility
What is a radial trachelectomy?
This involves removal of the cervix, the upper vagina and pelvic lymph nodes.
What is management of cervical cancer stage 2B-4A (locally advanced disease)?
Chemotherapy and radiation is 1st line
What is management of cervical cancer stage 4A (metastatic disease)?
Combination chemotherapy - surgery, radiotherapy, chemotherapy and palliative care
What is the 5 year survival rate of stage 1A and stage IV?
1A –> 98%
4 –> 15%
Management of women with advanced or incurable cervical cancer?
The goal should be to treat the following issues:
- Pain: analgesia, nerve-blocking therapies or spinal therapy
- Renal failure: conservative management, percutaneous nephrostomy, retrograde stenting
- Bleeding and thrombosis
- Malodour
- Lymphoedema
What is pelvic exenteration?
Pelvic exenteration is an operation that may be used in advanced cervical cancer. It involves removing most or all of the pelvic organs, including the vagina, cervix, uterus, fallopian tubes, ovaries, bladder and rectum.
It is a vast operation and has significant implications on quality of life.
Who is offered the HPV vaccination?
Recommended for girls and boys aged 12 to 13 (ideally given before they become sexually active)
Now 1 dose.
What is the current NHS vaccine against HPV? What 4 strains does it protect against?
Gardasil
6, 11, 16, 18
What are strains 6 and 11 of HPV responsible for?
Genital warts
What are strains 16 and 18 of HPV responsible for?
Cervical cancer
What is Bevacizumab (Avastin)? What is it used in? What does it target?
A monoclonal antibody that may be used in combination with other chemotherapies in the treatment of metastatic or recurrent cervical cancer.
It targets vascular endothelial growth factor A (VEGF-A), which is responsible for the development of new blood vessels
What hormone is endometrial cancer dependent on?
Oestogen
What is the endometrium?
Lining of the uterus
What is the most common type of endometrial cancer?
Adenocarcinoma (80%)
What does ‘oestrogen-dependent cancer’ mean?
oestrogen stimulates the growth of cancer cells.
A woman presenting with postmenopausal bleeding has what until proven otherwise?
Endometrial cancer
Need a 2-week-wait urgent cancer referral
What age group does endometrial cancer normally affect?
Mainly affects post-menopausal individuals (91% of cases in over 50s)
In resource-abundant countries, what is the most common gynaecological malignancy?
Endometrial cancer