Cervical cancer Flashcards
What is the age range and frequency of cervical cancer screening in women?
- 25-49 years: 3 yearly
- 50-64 years: 5 yearly
When are women over the age of 65 screened for cervical cancer?
Only if haven’t been screened since age of 50 or have had recent abnormal tests
What are the benefits of screening older women for cervical cancer?
Substantial reduction in incidence of and mortality from cervical cancer (less beneficial <30)
What equipment and set up is used in cervical screening?
Speculum (plastic or metal) inserted vaginally to view the squamocolumnar junction of the cervix
Which part of the cervix is exposed and swabbed during screening?
Squamocolumnar junction exposed; swab taken from whole of the transformation zone
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What is the method of choice used to triage a high-risk HPV found on cervical screening?
Liquid-based cytology (LBC)
How does the process of cervical screening take place?
- Brush used, rotated against squamous columnar junction
- [Head of brush containing cells broken into pot containing special preservative liquid, head sent to lab in pot (SurePath) OR
- Brush rinsed in preservative to wash cells into pot, then discarded (ThinPrEP)]
- don’t know if it’s the same for screening for high risk HPV
In the event of finding high-risk HPV on cervical screening, what will be performed and what is being looked at for?
Liquid based cytology performed; cells analysed to look for abnormalities in appearance of nucleus and other aspects of cell morphology (dyskaryosis)
What are 7 possible outcomes from a test sample following liquid based cytology triage of a postive for hrHPV screen result?
- Negative - 94%
- Inadequate - 2.2%
- Borderline - 3.4%
- Mild dyskaryosis - 1.5%
- Moderate dyskaryosis - 0.4%
- Severe dyskaryosis - 0.6%
- Glandular neoplasia - <0.1%
What is meant be a ‘negative’ test result for liquid based cytology?
Endocervical cells with normal nuclei
What is meant by an ‘inadequate’ test result?
Insufficient/ unsuitable material e.g. vaginal cells, endocervical cells, insufficient cells, unlabelled or inadequate fixation in lab
What is meant by a ‘borderline’ test result?
Abnormal nuclei but can’t be certain indicative of dyskaryosis, most revert to normal smears
What is meant by a ‘mild dyskaryosis’ test result?
Normally revert to normal, equates to cervical intraepithelial neoplasia (CIN) 1, cancer very unlikely
What is meant by a ‘moderate dyskaryosis’ test result?
Equates to CIN (cervical intraepithelial neoplasia) 2, pre-cancerous condition with intermediate probability of developing into cancer
What is meant by a ‘severe dyskaryosis’ test result?
CIN (cervical intraepithelial neoplasia) 3, higher risk, less than 0.1% will show nuclear and other cellular changes suggestive of carcinoma (carcinoma in situ)
What is meant by a ‘glandular neoplasia’ test result?
Occasionally abnormalities of glandular cells seen suggestive of adenocarcinoma in situ, of cervix, endometrial adenocarcinoma, or adenocarcinoma of organ outside uterus
What are 3 actions to take if the cervical screening test result is negative?
- Investigate and manage incidental findings e.g. infections
- Ensure patient informed of result
- Recall as appropriate for negative result, depending on age and previous screening history
What are 2 actions to take if the cytology test result for cervical screening is inadequate?
- repeat sample immediately after treating any infection, preferably wihin 3 months but as soon as convenient
- if persistently inadequate cytology (2 consecutive inadequate samples) assess with colposcopy
Depending on the region of the UK, what will be the next step if a cervical screening test result is borderline or mild dyskaryosis?
- In England and Northern Ireland, these will automatically be tested for HPV. If positive, referrred for colposcopy
- HPV DNA test (HPV triage) using original sample
- In Scotland and Wales, borderline/mild repeat after 6 months or referred for colpscopy
What action should be taken if a cervical screening test result shows moderate dyskaryosis?
Refer for urgent colposcopy (2 weeks)
What action should be taken if a cervical screening test result shows severe dyskaryosis?
Refer for urgent colposcopy (2 weeks)
What will be done with regards to screening following treatment for abnormal smear results?
- HPV test and cytology on follow-up smear, called ‘test of cure’ 6 months after initial treatment
- If HPV negative, returned to normal recall
- If HPV positive, or moderate/severe dyskaryosis, woman referred back to colposcopy for further treatment
What are the 4 high risk types of HPV for cervical cancer?
HPV 16, 18, 31, 33
What should be done if one of the high risk type of HPV (16, 18, 31, 33) is present on cervical screening?
Refer for colposcopy straight away
What are the benefits of HPV DNA testing?
Leads to earlier detection of clinically relevant CIN grade 2 or worse, which improves protection against CIN grade 3 or worse and cervical cancer when treated
In what proportion of cervical cancers are high risk HPV types (16, 18, 31, 33) present?
close to 100%
What is the course of action if a patient shows CIN 1 at colposcopy (following an abnormal cervical smear)?
- Followed up at 12 months with cytology and HPV testing
- if HPV positive, referred to colposcopy irrespective of cytological changes
- If high grade cytological changes, HPV testing not done and referred back to colposcopy
What should be done for follow up if the results of colposcopy show cervical glandular intraepithelial neoplasia (CGIN) and the patient has received treatment?
Follow up at 6 months; test of cure ± colposcopy
Tests (test of cure and colposcopy) repeated again after 12 months, even if test of cure showed normal cytology and negative for HPV
When was the HPV vaccination introduced and for whom?
September 2008 for girls 12-13
What proportion of cases of cervical cancer occur in women under the age of 45 years?
50%
Within which age range is the incidence of cervical cancer highest?
25-29 years
What are the 2 types of cancer that cervical cancer can be grouped into?
- Squamous cell cancer (80%)
- Adenocarcinoma (20%)
What are 3 possible features of cervical cancer?
- May be detected during routine cervical cancer screening
- Abnormal vaginal bleeding: postcoital, intermenstrual, postmenopausal
- Vaginal discharge
In addition to high risk HPV serotypes, what are 7 other risk factors for cervical cancer?
- Smoking
- Human immunodeficiency virus (HIV)
- Early first intercourse
- Many sexual partners
- High parity
- Lower socioeconomic status
- Combined oral contraceptive pill
What is the mechanism of HPV 16 and 18 causing cervical cancer?
- Produce oncogenes E6 (HPV 16) and E7 (HPV 18) genes
- E6 inhibits the p53 tumour suppressor gene
- E7 inhibits RB suppressor gene
What is a drawback of the UK’s cervical cancer screening programme?
Cervical adenocarcinomas (20% of cases) are frequently undetected by screening
What is the main aim of cervical cancer screening, and what is it not?
Detect pre-malignant changes rather than detect cancer
What is the rule about cervical screening and pregnancy?
Usually delayed until 3 months post-partum unless missed screening or previous abnormal smears
Which women may wish to, and can, opt out of cervical cancer screening?
Those who have never been sexually active - very low risk of developoing
How does the new LBC (liquid-based cytology) technique of smears differ from the old screening test?
The old technique involved smearing the sample only a slide, but now it is either rinsed into the preservative fluid or the brush head is removed into the sample bottle containing the preservative fluid
What are 2 advantages of LBC (liquid-based cytology) over the old, Papinacolaou (Pap) test?
- Reduced rate of inadequate smears
- Increased sensitivity and specificity
At what point is it said to be the best time in the menstrual cycle to take a cervical screening test?
Mid-cycle (limited evidence but advice given by NHS)
What are the 2 other most common subtypes of HPV in addition to the carcinogenic ones (16, 18, 31 and 33) and what do they cause?
6 & 11, associated with genital warts
What do the changes that HPV-infected endocervical cells undergo result in?
Koilocytes (right of image)
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What are 4 features of koilocytes (develop from HPV-infected endocervical cells)?
- Enlarged nucleus
- Irregular nuclear membrane contour
- Nucleus stains darker than normal - hyperchromasia
- Perinuclear halo may be seen
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What proportion of all cervical screening tests are abnormal?
5% of all smears
What time frame is the colposcopy following cervical cytology triage showing moderate / severe dyskaryosis or suspected invasive cancer?
URGENT - 2 WEEKS
What cells are affected by human papillomavirus (HPV)?
Keratinocytes of skin and mucous membranes
What proportion of anal cancers are linked to human papillomavirus (HPV)?
around 85%
What proportion of vulval and vaginal cancers are linked to HPV infection?
50%
What proportion of mouth and throat cancers are linked to HPV infection?
20-30%
Why did Gardasil (type of HPV vaccination) replace Cervarix as the vaccination offered in 2012?
Cervarix protected against HPV 16 & 18 but not 6 and 11 - cause significant disease burden from genital warts, Gardasil protects all
From which year were boys given the HPV vaccination in addition to girls?
September 2019
Do parents have a say in girls and boys receiving the HPV vaccination?
Information on NHS website and given to parents make it clear they may receive it against parental wishes
How is the HPV vaccination given?
2 doses: girls have second dose between 6-24 months after the first, depending on local policy
In addition to girls and boys in Year 8 (age 12-13) in school, who else should be offered the HPV vaccination?
Men who have sex with men under 45, to protect against anal, throat and penile cancers
What adverse reaction is common with HPV vaccines?
Injection site reactions
What determines the management of cervical cancer?
FIGO staging and wishes of the patient to maintain fertility
What type of staging is used for cervical cancer?
FIGO staging: International Federation of Gynaecology and Obstetrics staging
What is stage IA of FIGO staging for cervical cancer?
- Confined to cervix, only visible by microscopy and less than 7mm wide
- A1: <3mm deep
- A2: 3-5mm deep
What is stage IB of FIGO staging for cervical cancer?
- Confined to cervix, clinically visible or larger than 7mm wide:
- B1: <4cm diameter
- B: >4cm diameter
What is stage II of FIGO staging for cervical cancer?
- Extension of tumour beyond cervix but not to the pelvic wall
- A= upper two thirds of vagina
- B= parametrial involvement
What is stage III of FIGO staging for cervical cancer?
- Extension of tumour beyond the cervix and to the pelvic wall
- A= lower third of vagina
- B= pelvic side wall
- NB: any tumour causing hyronephrosis or non-functioning kidney is considered stage III
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What is stage IV of FIGO staging for cervical cancer?
- 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 is the gold standard of treatment for stage IA cervical tumours?
Hysterectomy ± lymph node clearance
What treatment of stage IA tumours can be performed for those wishing to maintain fertility (so don’t want hysterectomy)?
Cone biopsy with negative margins
What is the treatment for IA2 stage cervical cancer?
Hysterectomy + nodal clearance and nodal evaluation
Radical trachelectomy is also an option: removes cervix and upper part of vagina, parametrial tissue (surrounds lower end of uterus), pelvic lymph nodes
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What is the management of stage IB1 cervical tumours?
radiotherapy (bracytherapy or external beam) with concurrent chemotherapy (cisplatin most common)
What is the management of IB2 tumours?
Radical hysterectomy with pelvic lymph node dissection
What is the management of stage II and III cervical cancer tumours?
- Radiation (brachytherapy and external beam) with concurrent chemotherapy (cisplatin)
- If hydronephrosis (stage III), nephrostomy should be considered
What is the management of stage IV cervical tumours?
Radiation and/or chemotherapy is the treatment of choice; palliative chemo may be best option for stage IVB
What is the management of recurrent cervical cancer?
- Primary surgical treatment: offer chemoradiation or radiotherapy
- Primary radiation treatment: offer surgical therapy
- i.e. change tack
What is the prognosis of cervical cancer dependent on?
FIGO staging: see table
5 year survival - I: 96%, down to IV: 5%
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What are 3 complications of surgical treatment of cervical cancer?
- Standard complications e.g. bleeding, damage to local structures, infection, anaesthetic risk
- Cone biopsies and radical trachelectomy may increase risk of preterm birth in future pregnancies
- Radical hysterectomy may result in a ureteral fistula
What are 5 short-term complications of radiotherapy to treat cervical cancer?
- Diarrhoea
- Vaginal bleeding
- Radiation burns
- Pain on micturition
- Tiredness/weakness
What are 3 long-term complications of radiotherapy to treat cervical cancer?
- Ovarian failure
- Fibrosis of bowel/skin/bladder/vagina
- Lymphoedema
What is cervical screening looking for (as of March 2020)?
Looking for the presence of high-risk HPV - as found to be more sensitive than immediate liquid-based cytology
What are the 2 possible results of cervical screening and what is done as a result of each?
- negative for high risk HPV - recalled for routine screening
- positive - liquid based cytology performed
What are the 2 possible results of liquid based cytology following a positive cervical screen for high risk HPV? What is done as a result of each?
- Normal cytology - recalled for screen in 12 months
- Abnormal cytology - referred for colposcopy
How can the transformation zone of the cervix be identified to take a swab?
visual inspection as there is a change in colour and texture from the pale, pink, shiny, smooth surface of the ectocervix to a reddish, granular appearance of the columnar cells that line the endocervical canal.
What else should you do when taking a cervical swab for screening and what could this lead to?
Visual inspection - if any suspicious changes, gynaecology referral
If HPV is positive but cytology normal, how many times can you recall for screening for quickly before changing tack?
- recall for HPV swab in 12 months
- if positive and cytology normal 3 times (including first swab, so 24months later from first) –> colposcopy