Cervical cancer & CIN (incl. colposcopy, LLETZ) Flashcards
What is the most important factor in the development of cervical cancer?
Human papillomavirus (HPV), particularly serotypes 16,18 & 33
When does cervical cancer present?
At least 50% occur in women <45yrs
Most common in 25-29 year olds
What is the most common type of cervical cancer? What is the second?
- squamous cell cancer (80%)
- adenocarcinoma (20%)
How does cervical cancer present?
Asymptomatic - may be detected during routine cervical cancer screening
Symptomatic -
- abnormal vaginal bleeding: postcoital, intermenstrual or postmenopausal bleeding
- vaginal discharge
What are the risk factors for development of cervical cancer?
- HPV 16, 18 and 33
- smoking
- HIV
- early first intercourse, many sexual partners
- high parity
- lower socioeconomic status
- COCP (previously debated but now proven)
What is the pathophysiology of HPV in cervical cancer?
HPV 16 & 18 produces the oncogenes E6 and E7 genes respectively
- E6 inhibits the p53 tumour suppressor gene
- E7 inhibits RB suppressor gene
Which HPV strains cause cervical cancer vs genital warts?
6 & 11 - causes genital warts
16 & 18 - linked to a variety of cancers, most commonly cervical cancer - HPV infection is linked to 99.7% of cervical cancers
What other cancers is HPV infection linked to?
- >99.7% of cervical cancers
- ~85% of anal cancers
- ~50% of vulval and vaginal cancers
- ~20-30% of mouth and throat cancers
How many deaths does UK screening for cervical cancer prevent?
Prevents 1,000-4,000 deaths per year
What is the aim of cervical cancer screening?
To detect pre-malignant changes rather than to detect cancer
What is a major disadvantage of the cervical screening programme?
Cervical adenocarcinomas, which account for around 15% of cases, are frequently undetected by screening
Who is screened for cervical cancer? How often?
Smears are offered to all women between ages of 25-64 years old:
- 25-49 years: 3-yearly screening
- 50-64 years: 5-yearly screening
cervical screening cannot be offered to women over 64 (unlike breast screening, where patients can self refer once past screening age)
Can patients aged 65 self-refer for cervial cancer screening?
No - cervical screening cannot be offered to women over 64 (unlike breast screening, where patients can self refer once past screening age)
If a women is pregnant, can cervical cancer screening still be carried out?
Cervical screening in pregnancy is usually delayed until 3 months post-partum unless missed screening or previous abnormal smears.
Do lesbians or women who are not sexually active need to have cervical cancer screening?
Women who have never been sexually active have very low risk of developing cervical cancer therefore they may wish to opt-out of screening
Lesbian women should still take up screening as HPV can be transmitted by other types of sex and from partners who previously had heterosexual relationships. Unfortunately uptake is x10 worse in lesbian patients.
What type of smear is used nowadays?
Liquid-based cytology (LBC) is more commonly used than Papanicolaou (Pap) smears
Rather than smearing the sample onto a slide the sample is either rinsed into the preservative fluid or the brush head is simply removed into the sample bottle containing the preservative fluid.
What is the advantage of LBC over Pap smears?
- reduced rate of inadequate smears
- increased sensitivity and specificity
In relation to the mestrual cycle, when is the best time to take the sample?
Mid-cycle - although there is limited evidence to support this.
“The NHS has now moved to an HPV first system” - what does this mean in relation to cervical cancer screening?
i.e. a sample is tested for high-risk strains of HPV (hrHPV) first and cytological examination is only performed if this is positive.
What is the management of sample negative for hrHPV?
Return to normal recall
Except if:
- Test of cure pathway for CIN1-3 - 6 month recall
- Untreated CIN1
- Incompletely excised CGIN (cervical glandular intraepithelial neoplasia)/ stratified mucin producing intraepithelial lesion (SMILE)
What is the management of a positive hrHPV patient?
–> cytology
If the patient is hrHPV +ve and cytology is abnormal, what is the management?
–> colposcopy
What results does abnormal cytology include?
- borderline changes in squamous or endocervical cells.
- low-grade dyskaryosis.
- high-grade dyskaryosis (moderate).
- high-grade dyskaryosis (severe).
- invasive squamous cell carcinoma.
- glandular neoplasia
What is the mangement of a hrHPV+ve and normal cytology patient?
–> repeat test at 12 months
What is the mangement of a hrHPV+ve and normal cytology patient initially, who is then:
- hrHPV +ve and cytology still normal at 12 months
- hrHPV -ve
-
if the repeat test is still hrHPV +ve and cytology normal → further repeat test 12 months later (i.e. at 24 months)
- If hrHPV -ve at 24 months → return to normal recall
- if hrHPV +ve at 24 months → colposcopy
- if the repeat test is now hrHPV -ve at 12months → return to normal recall
What is the management of an inadequate sample at two different occasions?
- First, repeat the sample within 3 months
- Then, if two consecutive inadequate samples then → colposcopy
A 25-year-old undergoes a cervical smear test as part of the UK cervical screening programme. Her test results return as an ‘inadequate sample’. As such, she undergoes a repeat cervical smear 3 months later, which also returns as an ‘inadequate sample’.
What is the most appropriate action?
Colposcopy
A 53-year-old woman attends her GP surgery for a routine cervical smear. Based on the initial high-risk human papillomavirus (hrHPV) result, she is invited for a repeat smear in a further 12 months’ time. At this repeat smear, she is informed that the hrHPV result is now negative. Her past medical history is unremarkable.
What is the most appropriate management option?
Repeat smear in 5 years
Age 25–49 years — screening every 3 years
Age 50–64 years — screening every 5 years
What is the rationale for doing cervical hrHPV test and cytology 3 times in 24months if the first result is hrHPV positive with normal cytology?
90% of HPV+ve patients will clear the virus within 2 years; if persisting over 2 years you should be more worried that it has been there long enough for cytological changes to occur.
How often do HIV positive patients needs to have cervical smears?
Every year - due to decreased clearance of HPV and risk of false negative cytology results.
HIV positive women who have low-grade lesions (CIN1) do not clear them + can progress to high-grade CIN or cervical cancer. Even if effectively treated with antiretrovirals there is high risk of abnormal cytology and an increased risk of false-negative cytology.
What is the management of patients who have been treated for CIN1, CIN2 or CIN3?
Invite 6 months after treatment for a test of cure to repeat cervical sample in the community.
What is the most common management of cervical intraepithecial neoplasia (CIN)?
LLETZ - large loop excision of transformation zone
Alternatively cryotherapy may be used
Define LLETZ.
LLETZ is the most common treatment for cervical intraepithelial neoplasia. It uses a thin wire loop with an electrical current to remove the affected area of the cervix.
AKA loop electrosurgical excision procedure (LEEP)
What are the indications for LLETZ?
CIN2&3 lesions
OR persistent CIN1 - beyond 2 years
OR CIN lesions that can not be treated by cryotherapy
OR persistently abnormal cytology in the absence of any lesion visible on colposcopy
What is the management of CIN1?
It’s unlikely the cells will become cancerous and they may go away on their own; no treatment is needed and you’ll be invited for a cervical screening test in 12 months.
What are the complications of LLETZ?
- Bleeding (85%) for 2days-4 weeks
- Pain (67%)
- Watery, brown vaginal discharge (65%)
- Premature birth or late miscarriage - especially if >10mm of cervix removed
- Cervical stenosis
- Failure of treatment (10%) and cell changes return
Rare:
- Psychological distress
- Dyspareunia
- Bleeding post-coitally
- Pelvic pain - 5% still have pain after 5 years
What are the three types of CIN? Where is the disease confined to in all three?
CIN = Disease confined to the epithelium
- CIN I: disease confined to the lower third of the epithelium.
- CIN II: disease confined to the lower and middle thirds of the epithelium.
- CIN III: affecting the full thickness of the epidermis.
When does CIN become invasive cancer?
If it breaches the epithelial basement membrane at any point –> invasive cancer
- If deepest part is <5mm from surface = micro-invasive carcinoma*
- If it extends >5mm or is wider than 7mm = invasive carcinoma requiring formal staging*
What is the staging for cervical cancer called?
What is management of cervical cancer based on?
FIGO staging
Management determined by the FIGO staging + the wishes of the patient to maintain fertility.
Describe the staging of cervical cancer.
IA - Confined to cervix, only visible by microscopy + <7 mm wide:
- A1 = < 3 mm deep
- A2 = 3-5 mm deep
IB - Confined to cervix, clinically visible OR >7 mm wide:
- B1 = < 4 cm diameter
- B2 = > 4 cm diameter
II - Extension of tumour beyond cervix but not to the pelvic wall
- A = upper two thirds of vagina
- B = parametrial involvement
III - Extension of tumour beyond the cervix and to the pelvic wall
- A = lower third of vagina
- B = pelvic side wall
IV - Extension of tumour beyond the pelvis OR involvement of bladder or rectum
- A = involvement of bladder or rectum
- B = involvement of distant sites outside the pelvis
What stage is this?
“tumour causing hydronephrosis or a non-functioning kidney”
Any tumour causing hydronephrosis or a non-functioning kidney is considered stage III
What is the management of stage 1 cervical cancer?
- Gold standard?
- For patients wishing to maintain fertility?
Gold standard =
- hysterectomy
- +/- lymph node clearance
- +/- nodal clearance if 1A2
Fertility maintained =
- cone biopsy with negative margins maintained
- close follow up
- +/- node evaluation if 1A2
- OR radical trachelectomy if 1A2
What is radical trachelectomy?
Surgery to remove most of the cervix and the upper part of the vagina.
The womb is left in place and so it may be possible concieve afterwards
What is the management of 1B tumours?
1B1 = radiotherapy +concurrent chemotherapy
- Radiotherapy may either be brachytherapy or external beam radiotherapy
- Cisplatin is the commonly used chemotherapeutic agent
1B2 = radical hysterectomy with pelvic lymph node dissection
What is the management of stage II or III tumours?
II and III = radiotherapy + concurrent chemotherapy
If hydronephrosis, + nephrostomy
What is the management of stage IV tumours?
Radiation +/- chemotherapy is the treatment of choice
Palliative chemotherapy for stage IVB
If there is treatment relapse what options are avaialble?
If primary treatment was surgical: offer chemoradiation or radiotherapy
If primary treatment was radiation: offer surgery
What is the prognosis of cervical cancer depending on FIGO staging?
Stage 1 has 96% 5-year survival but this falls to 54% with stage 2
What are the complications of treatment for cervical cancer?
Usual complications - bleeding, damange to local structures, infection, anaesthetic complication
Cone biopsy and radical trachelectomy - may increase risk of preterm birth in future pregnancies
Radical hysterectomy - may cause ureteral fistula
Radiotherapy complications - short and long term
What are the short and long-term complications of radiotherapy for cervical cancer?
Short-term:
- Bleeding PV
- Diarrhoea
- Radiation burns
- Pain on micturition
- Tiredness/weakness
Long-term:
- Fibrosis of bowel/skin/bladder/vagina
- Lymphoedema
- Ovarian failure
What type of prevention strategy is available for prevention of cervical cancer? Who is it offered to?
HPV vaccination - introduced in 2008 and protects against 16&18 (Cervarix) and also 6&11 (in Gardasil)
Offered to:
- all 12-13 year old boys and girls in school in 2 doses 6-24 months apart.
- MSM <45 years old to protect against anal, throat and penile cancers
If a 12/13 year old’s parents refuse the HPV vaccination but the child requests it what happens?
NHS website make it clear that the daughter may receive the vaccine against parental wishes
What is a common complication of HPV vaccination?
Injection site reactions
How do you manage cervical cancer if diagnosed during pregnancy?
Treatment may be delayed until a viable fetus can be delivered (provided this delay is only for a few weeks)
or a therapeutic abortion may be necessary.
