3.1 Premalignant gynaecological conditions Flashcards
What is the criteria for screening to be good and useful?
Health problem: Must be an important and relevant problem
Natural history: Adequately understood and recognisable latent/early stage
Diagnosis: Availability of suitable test and acceptability to general population
Treatment: Availability of facilities and agreed policy on whom to treat
Case finding: Economically balanced (in relation to possible expenditure on medical care as a whole) and continuing process (not ad-hoc)
Cervical cancer may result mainly from __________ or __________ → both treated the same way:
• Other types of cervical cancer include adenosquamous carcinoma (5 – 6%), small cell cancer (~3%), and other rarer types (e.g. lymphomas, sarcomas)
squamous lesions (squamous cell carcinoma) or glandular lesions (adenocarcinoma)
what is a CIN 1 squamous cell cervical carcinoma?
mildly atypical cells confined to the lower 1/3 of the epithelium
what is a CIN 2 squamous cell cervical carcinoma?
atypical cellular changes affecting the basal 2/3 of the epithelium
what is a CIN 3 squamous cell cervical carcinoma?
cellular changes affecting more than 2/3 of the epithelium (including full-thickness lesions) → slow transformation into cancer
what does CGIN stand for?
cervical glandular intraepithelial neoplasia
what does AIS stand for?
adenocarcinoma in situ
What are the high risk HPV types?
HPV type 16, 18 (most prevalent; causing 70% of cervical cancers):
• Type 16: closely related to types 31 & 33 (high risk types)
• Type 18: closely related to types 45 & 51
What are the low risk HPV types?
HPV type 6, 11, 42, 43
Cervical cancer/CIN only develops with the necessary precursor of an HPV infection.
1) Acute HPV infection Virus exclusively infects the __________________
• Disrupts cell cycle control → promotes uncontrolled cell division and accumulates genetic damage
2) Viral persistence: Virus is not cleared from the infected cells
3) Clonal progression ________________ results from cellular changes and proliferation of the infected cells
4) Invasive cervical cancer Integration of the HPV genome into the host genome → viral DNA affects normal epithelial cells and transforms them into ___________________
metaplastic squamous epithelium of the transformation zone (TZ);
Pre-cancer (CIN lesions) ;
dyskaryotic cells (dyskaryosis)
The transformation zone (TZ) of the cervix is the area between the __________________ and ______________→ site of squamous metaplasia:
• Vaginal environment is acidic during the reproductive year/pregnancy → _________________ is involved in squamous metaplasia
• ________________ in the area of ectropion (where columnar cells form on the ectocervix) are exposed to acidic environment → repeated destruction → eventually replaced by newly formed metaplastic epithelium
• Metaplastic regions may become cancerous under certain exposures
original squamocolumnar junction and the new squamocolumnar junction;
oestrogen-induced acidity;
Columnar epithelial cells
Squamous metaplasia in cervical cancer is cellular adaptation occurring in 3 stages
1) Reserve cell hyperplasia: Reserve cells in the _________________ start to divide
2) Immature squamous metaplasia: Proliferation to form multilayer of undifferentiated cells → surface layer of _______________
• Most susceptible to carcinogens (most cervical cancers arise here)
3) Mature squamous metaplasia: Undifferentiated cells differentiate into __________________ (almost indistinguishable from the original squamous epithelium)
endocervical epithelium (basal layer);
mucinous columnar cells;
mature squamous epithelium
How is a conventional pap smear done?
Vaginal speculum used to hold the vaginal walls apart → sample of cells collected from the cervix using a small cone-shaped brush or tiny wooden spatula → smeared onto slide
Why is liquid based cytology > pap smear?
Replaces conventional Pap smears (overcomes specimen quality issues):
• Allows ancillary testing of HPV, gonorrhoea or chlamydia from the same medium
How does thin prep (liquid based cytology) work?
collection device agitated to dislodge cervical cells into the medium
How does sure path (liquid based cytology) work?
collection device deposited into vial and both are sent to the lab for processing (less expensive)
What are the categories of British Society for Colposcopy and Cervical Pathology under the results of pap smear?
- Normal cells: represents 90% of obtained results
- Borderline changes (< 5%): cells show some abnormality (too mild to be classified as dyskeratosis) → most resolve spontaneously
- Mild dyskaryosis (< 5%): most resolve spontaneously
- Moderate dyskaryosis (0.5%) and severe dyskaryosis (0.5%)
What are the categories of Bethesda under the results of pap smear?
- Low-grade squamous intraepithelial lesion (LSIL): incorporates borderline changes and mild dyskaryosis
- High-grade squamous intraepithelial lesion (HSIL): incorporates moderate and severe dyskaryosis
High risk HPV (HR-HPV) testing is defined by a ________________________:
• 15 – 20% of women with borderline/mild abnormalities on Pap smear have significant abnormalities which require treatment
• If they test negative for HR-HPV, they can safely return to normal Pap smear screening
triage of borderline/low grade abnormalities in cervical smears to identify high-risk HPV infections
What are the uses of HR- HPV testing?
- triaging: Helps to avoid unnecessary anxiety/investigations with effective use of available resources
- Primary screening for cervical cancer: Replacement of the traditional Pap smear with HR-HPV as a primary screening modality is being investigated:
• Lower specificity than Pap smear
• May not be useful in younger sexually active women (most likely positive anyway) - Test of cure after CIN treatment HR-HPV status tested after treatment to streamline management:
• 6 months post-initial treatment: repeat Pap smear, HR-HPV
• If negative HR-HPV: safely return to normal screening
What are the indications of colposcopy?
abnormal screening result (HR-HPV test positive + mild/moderate/severe dyskaryosis)
Steps of colposcopy
1) Application of _____________ to the transformation zone:
• Mapping the site and grade of any area of abnormal cells → via reversible precipitation of nuclear proteins (white-staining)
• Abnormal dyskaryotic cells: possess greater amounts of _____________ (higher grades of abnormality) → stains more __________
2) Gentle application of after _________________:
• Identification of the complete area of abnormality → via reaction of iodine with ______________
• Normal squamous cervical cells stain _________; abnormal cells do not stain
3) Small biopsy from abnormal areas → for histological confirmation of CIN and further evaluation and treatment
mild acetic acid;
nuclear matter;
densely white ;
water based solution of iodine
intracellular glycogen ;
brown;
What does one do if HR- HPV testing is positive?
colposcopy
What does one do if HR- HPV testing is negative?
no action required
PREVENTION OF CERVICAL CANCER
The HPV vaccine contains virus-like particles (VLPs) which are _____________, and are used for prevention of cervical cancer:
• Antibodies (humoral immunity) are generated against the ____________ on outer surface + local cell-mediated immunity
o Associated with lesion regression and protection against further infection with the same genotype of HPV
• 2 vaccines are currently approved under the National Immunisation Programme:
capsid proteins without viral DNA (non-infectious);
conformational epitopes on the major coat/capsid protein L1
What strains of HPV does gardisil 4 target?
VLP L1 of HPV 6, 11, 16, 18
what is the adjuvant for gardasil 4?
Aluminium (225μg amorphous aluminium hydroxyphosphate sulfate (AAHS))
what is the usage for gardasil 4?
Females and males 9 – 26 years old
what is the dosingt for gardasil 4?
- 3 doses via IM injection (0, 2, 6 months) for 9 – 26 years old
- 2 doses via IM injection (0, 6 months) for 9 – 13 years old
What strains of HPV does cevarix target?
VLP L1 of HPV 16, 18
what is the adjuvant for cevarix?
AS04 (500μg aluminium hydroxide + 50μg 3-deacylated monophosphoryl lipid A)
what is the usage for cevarix?
Females 9 – 25 years old
what is the dosingt for cevarix?
- 3 doses via IM injection (0, 1, 6 months) for 9 – 25 years old
- 2 doses via IM injection (0, 6 months) for 9 – 14 years old
what are the common side effects of hpv vaccine?
Pain, swelling, itching, redness at site of infection, headache, fever, nausea
What strains of HPV does gardisil 9 target?
The FDA approved the nonavalent HPV vaccine (Gardasil 9®) in 2014, which is active against HPV types 6, 11, 16, 18 + additional 5 high-risk HPV types 31, 33, 45, 52, 58:
• Adjuvant: 500μg AAHS
when is treatment for CIN indicated?
High percentage of lower grade dysplasia lesions spontaneously resolve (especially in young patients) → treatment is only indicated in cases of persistent dysplasia or those associated with positive HR-HPV tests
What is surgical treatment for CIN?
excision of transformation zone (LLETZ: large loop excision of transformation zone) or using ablative techniques (e.g. laser vaporisation, thermocoagulation, cryotherapy)
Endometrial cancer: 6th most common cancer in women worldwide (primarily a cancer of the developed world → incidence is double):
• Mainly affects ________________
• Most patients are diagnosed at the early stage (due to ___________________) → high survival rates
• No screening: screening tools (e.g. cytology, USS) have limited accuracy in evaluating normal population and are unlikely to decrease cancer-associated mortality
postmenopausal women (~60 years at diagnosis);
early presentation like postmenopausal bleeding
Ovarian cancer: Primarily occurs in developed countries:
• Most lethal of all gynaecological cancers (advanced stage by the time of presentation for >70% of women)
• No screening because _________________
no identifiable pre-cancer phase (no validated screening test for early stage)
Vaginal/ vulval cancer: Often do not cause early symptoms, but may be found during ___________________:
• No screening: very rare cancers (vaginal cancer occurs more often in _______________; vulval cancer accounts for only 1% of all genital cancers)
routine pelvic examinations and Pap smears;
women > 50 years
