JC103 (O&G) - Cervical cancer screening Flashcards
Cervical cancer
- Reasons to why it is suitable for screening
- High prevalence
- Suitable disease:
• Early treatment is effective
• Long progression from precancer lesions to invasive cancer - Suitable tests
• Minimally invasive sample collection
• Cervix is accessible to cytologic screening or HPV testing - Suitable screening programs (territory-wide Cervical Screening Programme)
- Cost-effective screening test
Personnel/ organisations involved in population-wide cervical cancer screening
Training and education of medical personnel, smear takers
Cytology pathology laboratory accreditation – QA
Colposcopy accreditation – QA
Audit (based on CSIS)
Target population for cervical cancer screening in HK
Start screening at age 25 or commencement of sexual life
Stop at age of 65
Screen women >65 years who:
Have never had a cervical smear, or
Request a cervical smear
Avoid cervical screening during pregnancy (induce anxiety)
Frequency of cervical cancer screening in HK
After 2 consecutive normal annual smears, screen at 3-yearly intervals
Annual screening for persons at high risk of developing cervical carcinoma more rapidly, eg. Immunosuppression, HIV
System for cervical smear screening in HK
Methods for increasing reach of screening program
Organized screening with central registry - Cervical cancer screening information system (CSIS) HK:
- Send reminders for screening
- Trace abnormal results and defaulters
Methods to increase reach Public education Health workers education Publicity (mass media) School education (young people) Clinics/ centres – Department of Health: Women’s health centre, Well Women Clinics, Family Planning Association Mobile units
Pap smear
- Sampling devices
- Site of sampling
- Sampling technique
- Storage and labeling method
Tools:
Wooden/ plastic Ayre’s spatula
Endocervical brush
Choose rize based on vagina: e.g. larger for multiparous
Site: cells from cervical os at transformation zone (squamocolumnar junction)
Technique:
- Push sampler gently and rotate around cervical os
- Rinse brush into vial for liquid- based cytology (LBC)/ fix immediately
- Discard spatula or brush
Storage:
- Label, check identity
- Fill request form with matched identity
Patient information contained on a request form for pap smear
Fill in request form properly with matched identity:
Clinical data (helps cytopathologist make the correct diagnosis)
Age
Last menstrual period/ duration of menopause
Parity
Contraceptive history
Drug/ medical history
Contraindications to pap smear
Blood in vagina or cervix (normal menstruation or other pathologies)
Obvious or gross growth on cervix (covered by necrotic cells, causing false negative cytology) - Biopsy indicated
Cervix cannot be seen
Causes of unsatisfactory pap smear
- Artifacts – air-dried (should fix immediately)/ too thick/ too scanty cells/ heavily blood- stained
- Marked inflammation/ infection (PMN+++ masks host cells)»_space;> treat infection and repeat
- Menopausal (atrophic epithelium cells look abnormal)»_space;> apply local estrogen and repeat
- Post-treatment (radiotherapy, chemotherapy)
Uterine cervix tumor types
Epithelial:
- Squamous cell tumors and precursors
- Glandular tumors and precursors
- Other epithelial tumors
Mesenchymal tumors and tumor-like conditions
Mixed epithelial and mesenchymal tumors
Melanocytic tumors
Lymphoid and haematopoetic tumors
Secondary tumors
Name the system that standardizes terminology & reporting of cervical cytology
The Bethesda system (TBS):
Merged Dysplasia and Carcinoma-in-situ into Squamous intraepithelial lesion (SIL):
behaviour, molecular virologic findings and morphologic features
Outline the classification systems for Epithelial** cervical cancer
3 main histological groups after classification
Atypical squamous cells
Of undetermined significance (ASC-US)
Cannot exclude HSIL (ASC-H)
Neoplasm:
1. Bethesda system (TBS): classify cytology by pathohistological features as
Low-grade squamous intraepithelial lesion (LSIL)
High-grade squamous intraepithelial lesion (HSIL)
2. WHO Classification of uterine cervix tumors: Specify CIN = cervical intraepithelial neoplasia as CIN-I to CIN-III, VAIN I- VAIN III and VIN I- VIN III**
3. WHO classification of female genital tumors: Specific as HPV-associated or HPV-independent
SCC:
SCC, HPV- associated
SCC, HPV- independent
SCC, NOS (not otherwise specified)
2 lab tests for HPV status of female genital tumors
HPV molecular testing
p16 IHC
7 types of uterine cervix glandular tumors (WHO)
Adenocarcinoma in-situ
- HPV associated type
- HPV independent type
Adenocarcinoma, HPV associated
Adenocarcinoma, HPV Independent
- Gastric type
- Clear cell type
- Mesonephric type
Adenocarcinoma, others
3 main groups of epithelial cervical cancer after classification
- Atypical squamous cells
Of undetermined significance (ASC-US) - most common smear result
Cannot exclude HSIL (ASC-H) - Squamous intraepithelial lesions (SIL)
Low-grade squamous intraepithelial lesion (LSIL)
High-grade squamous intraepithelial lesion (HSIL) - features of invasion - SCC:
SCC, HPV- associated
SCC, HPV- independent
SCC, NOS (not otherwise specified)
Atypical squamous cells of undetermined significance (ASC-US)
- Incident rate in population-wide pap smears
- Risk
- Management of ASCUS smear result
ASC-US
- Most common abnormality in screening population (60-80%), majority turns out as normal/ LSIL
Risk:
- progression into HSIL, Invasive epithelial cervical cancer (rare)
ASCUS: Repeat cytology at 6 months and 12 months
- Both normal = repeat cytology at 3 years
- ASCUS or above within 12 months = Colposcopy
HPV test as triage or co-testing
- High risk, HPV positive = Colposcopy
- High risk, HPV negative = Repeat co-testing or cytology at 3 years
Atypical squamous cells - Cannot exclude HSIL (ASC-H)
Risks
Proportion that turn out to be HSIL?
Risks:
Higher risk of oncogenic HPV DNA detection
Higher risk of underlying CIN 2 or worse (30- 40%) in biopsy compared to ASC-US
High proportion (24-94% in diff. studies) turned out to have HSIL (CIN II-III)
Types of atypical glandular cells/ precursors of adenocarcinoma
Atypical endocervical cells
- NOS or specify in comments
- favor neoplastic type
Atypical endometrial cells
- NOS or specify in comments
Atypical glandular cells:
- NOS or specify in comments
- favor neoplastic type
Endocervical adenocarcinoma in situ
- HPV associated
- HPV independent
Compare the histological difference between atypical glandular cells and adenocarcinoma-in-situ at cervix
Atypical glandular cells:
- Eccentric hyperchromatic nuclei with mucin vacuole
- microglandular hyperplasia
= benign lesion related to hormonal effect
Adenocarcinoma-in-situ
- Marked increased N/C ratio, nuclear overlapping, glandular configuration
= favor neoplastic lesion
Most common glandular cervical tumors in HK
Most common = precursor glandular lesions:
Atypical Glandular Cell-FN (favor neoplasia): 27-96% turned out to have HSIL (CIN2-3), AIS, Ca
AGC-NOS (not otherwise specified): 9-41% turned out to have HSIL (CIN2-3), AIS, Ca
AGC after confirmation tests:
9.2%: CIN II-III
4.3%: CIN I
5.7%: carcinoma of corpus (endometrial cancer)
2.8%: carcinoma of ovary (ovarian cancer)
2.1%: extragenital malignancies
1.4%: adenocarcinoma of cervix
Most common glandular cervical tumors in HK
**AGC-FN (favor neoplasia): 27-96% turned out to have HSIL (CIN2-3), AIS, Ca
*AGC-NOS (not otherwise specified): 9-41% turned out to have HSIL (CIN2-3), AIS, Ca
AGC after confirmation tests:
9.2%: CIN II-III
4.3%: CIN I
5.7%: carcinoma of corpus (endometrial cancer)
2.8%: carcinoma of ovary (ovarian cancer)
2.1%: extragenital malignancies
1.4%: adenocarcinoma of cervix
Glandular cervical cancer
Management of Atypical Glandular Cell smear result
AGC - endometrial cells: Endometrial sampling
- Positive = refer for treatment
- Negative: Colposcopy + biopsy + Endocervical sampling
All subcategories of AGC + negative endometrial sample for AGC- endometrial cells:
- Colposcopy + biopsy + Endocervical sampling
» lesion identified = treatment
» No lesion:
i. AGC favours neoplasia or Endocervical AIS = Diagnostic excisional conization and follow-up ultrasound pelvis to exclude adnexal pathology
ii. AGC-NOS: repeat cytology 6 monthly until 4 consecutive normal results OR Diagnostic excisional conization if abnormal cytology
List 4 advanced techniques for gynaecological cytopathology testing
Automation in cytology preparation
Liquid-based cytology (LBC)
Automated screening with imaging system, computer-assisted
Applications of molecular tests: IHC, ISH, DNA, HR-HPV tests**
Benefits of liquid based cytology LBC for cervical smears
Less unsatisfactory smear: more clarity, uniformity, reproducibility
Less reactive atypia
Increased definitive diagnosis of SIL
List oncogenic, high risk HPV subtypes
15-20 oncogenic (high risk - HSIL, CA): HPV 16, 18, 31, 33, 45, 51, 52, 58, 59 etc
HPV 16, 18 cause 70% of cervical cancer
Indications for direct colposcopy and biopsy
HPV 16 or 18 positive
Abnormal (HSIL), Regardless of HPV status
Abnormal (LSIL) HPV +ve
ASC-H
Inconclusive (ASC-US), High-risk HPV+
Outline 3 follow-up options for abnormal cervical smear
- Repeat smear and cytology or HPV test
- colposcopy and punch biopsy for histological diagnosis
- Take biopsy for obvious lesion e.g. endometiral/ endocervical
Management of ASC-US smear result
Repeat smear in 6 months, 12 months
Refer for colposcopy and biopsy if abnormality persists
OR
Triage with test for high-risk HPV
Positive = colposcopy
Negative = repeat cytology screening (co-testing or cytology) in 3 years
Management of ASC-H smear result
Refer colposcopy and biopsy
- 2 consecutive normal = back to normal routine
Obtain endocervical sampling if unsatisfactory colposcopy
- No lesion = repeat cytology every 6 months
- Persistent abnormal cytology = repeat colposcopy
Management of LSIL smear result
Refer colposcopy and biopsy
Co-testing for High risk HPV (hrHPV)
- HPV positive = colposcopy
- HPV negative = repeat co-testing in 12 months
Cytology
» Abnormal = colposcopy
» Both normal, = repeat co-testing or cytology in 3 years, then routine screening
Management of HSIL smear result
Refer colposcopy
If gross lesion seen = Punch biopsy
Immediate biopsy regardless of HPV status
Management of atypical glandular cells on cervical smear
Refer to colposcopy, endometrial biopsy and endocervical sampling (endometrial sampling first for AGC-Endometrial cells)
For AGC-FN or AGC- endocervical cells: if no significant pathology for source of abnormal cells»_space; Diagnostic cold knife cone biopsy/ conization
For AGC-NOS: Repeat 6-monthly until 4 consecutive normal results, then resume normal screening schedule
Management of adenocarcinoma in situ cervical smear result
Refer for colposcopy and biopsy +/- endocervical sampling and endometrial sampling
Cone biopsy if no lesions found
Colposcopy for cervical lesions
- Method
- Functions
- Sample area
Instrument:
- Magnify cervix 8-25X using binocular optic instrument
- 3-5% acetic acid: dense aceto-white lesions, abnormal vascular pattern, punctations and mosaic
- Adjunctive test (Schiller’s test): Lugol’s iodine negative (normal = dark; abnormal cannot be stained)
Functions:
- Punch biopsy of gross lesion if seen
- Visualize lesion
- Find vascular patterns
Sample area:
whole lesion and squamocolumnar junction
Management of unsatisfactory colposcopy sampling
Good sample needs squamocolumnar junction and whole lesion:
Squamocolumnar junction not seen: Obtain endocervical sampling:
- If no lesion identified, review material, repeat colposcopy with estrogen in menopausal women
- If lesion persists, diagnostic cone biopsy
- If abnormal cytology persists, repeat colposcopy
- If cytology is normal twice, back to routine screening
Whole lesion not seen = diagnostic cone biopsy
Management of low-grade CIN cervical smear result
Follow up every 6 months:
- Majority of low grade cervical intraepithelial neoplasia regressed spontaneously (over 2 years) - follow up till normal
- If persisted for 2 years - consider treatment
If patients not reliable for follow-up, can offer treatment at diagnosis
Treatment options of high grade cervical CIN
A. Ablative therapy (no histology): Cryotherapy (-50oC) to freeze the tissue Cold coagulation Diathermy Laser evaporisation
B. Excision therapy – cone biopsy for histology:
Knife
Laser
Large loop excision (electric) of the transformation zone of the cervix (LLETZ) – most commonly used:
C. Hysterectomy (rarely indicated)
Most common treatment options for high grade cervical CIN
Complication
Large loop excision (electric) of the transformation zone of the cervix (LLETZ)
Complications:
Intraoperative and postoperative bleeding (1-8%)
Infection
Cervical stenosis (1%)
Cervical deformity
Cervical incompetence
Premature rupture of membrane, premature labour, low birthweight
Monitoring method after treatment of high-grade cervical CIN
Repeat cervical smear at 6 month intervals till normal for 3 consecutive smears then annually
Treatment of early invasive cervical cancer
Radical hysterectomy with bilateral pelvic lymphadenectomy; or radiotherapy
Primary prevention of cervical cancer
Healthy lifestyle (do not smoke for better immunity)
Safer sex
HPV vaccines
Types of HPV vaccines
Vaccine types and HPV subtypes:
Bivalent - 16, 18
Quadrivalent - 16, 18, 6, 11
Nonavalent - 6/ 11/ 16/ 18/ 31/ 33/ 45/ 52/ 58 (5 additional oncogenic)
Benefits of higher HPV vaccination rate
Reduction in: Abnormal cervical cytology High-grade CIN Colposcopy examination Operative procedure for treatment of high-grade CIN
Target populations recommended for HPV vaccine in Hong Kong
Dosing regimens
Prophylactic HPV vaccines for women with no prior exposure to the virus (i.e. in never-sexually active women)
Women aged >15 = 3-dose regimen
Girls aged <15 = 2-dose regimen within 6-12 months
Should not be given to pregnant women
