Cervical Screening; the prevention of cervical cancer Flashcards
Age of peak prevalence of HPV infection
15-25 years old
Why is 15-25 years of age the peak prevalence from HPV infection?
Predisposed to sex
Multiple partners
The incidence of HPV infection in correlation with age
Prevalence declines with age
Prevalence in young women and men of HPV
approx. 30%
Lifetime risk exposure of HPV
75%
High risk HPV causes what type of cancers?
Cervix (>99% caused by HPV)
Penis (>40% caused by HPV)
Vulva/vaginal (>40% caused by HPV)
Anus (>90% caused by HPV)
Almost 100% of cervical cancer is caused by…
HPV
HPV stands for….
Human Papilloma virus
High rates of anal HPV are reported in….
MSM
Pathology of HPV infection in the cervix
Early HPV infections may be accompanied by mild changes in the epithelium
Abnormal growth of squamous cells detectable on smear called a squamous intraepithelial lesion (SIL)
HPV affects the basal cells
It doesn’t send out signals to the immune system like the common cold or flu etc
Abnormal cells detected on biopsy classified as cervical intraepithelial neoplasia (CIN)
Types of squamous intraepithelial lesion (SIL)
Low grade (LSIL) High grade (HSIL) Depending on how much of the cervical epithelium is affected and how abnormal the cells appear
Grading of CIN
Graded 1 to 3 according to the proportion of the cervix affected
What cells does HPV affect?
The basal cells
Stages of HPV infection into the cervix
stage I - infectious viral particles enter the skin through a break in the skin (called a micro-abrasion) which can be as small as 40 cells deep. They invade the basal cells where they can stay for several years with no ill effects but the women is a carrier and therefore a potential spreader of the disease
stage II (Grade I CIN)- the virus begins to mix with the cells DNA, replicates and starts to spread by invading other cells. The changes to cells can be observed as low grade pre cancerous lesions that can be picked up by screening and treated
Stage III (Grade 2 CIN) - the cells become more damaged and disorganised - resulting in a high grade lesion
Stage IV (Grade 3 CIN) - the high grade pre cancerous lesion grows and occupies almost the entire thickness of the skin
Stage 5 (invasive cancer) - all the cells have been infected and are completely disorganised producing an invasive cancerous growth tumour that can break through the inner layer of the skin and spread to other parts of the body
Stage 2 to stage 4 of HPV infection in the cervix are what kind of lesion?
Pre-cancerous lesions - cervical intraepithelial neoplasias (CIN)
How long can it take to clear the HPV?
2 - 3 years
What does CIN1/2 have the potential to progress to?
Cancer
Type of HPV infection with the highest risk
HPV 16/18
UK immunisation programme against HPV involves…
Quadravalent vaccine HPV 16/18/6/11
2 dose regime
Vaccinating girls between ages 16-18
Why is cervical cancer linked to cigarette smoking?
As nicotine is excreted in the cervical mucus
Scenarios in cervical smears where you would have to think about where you would sample
Pregnancy
Contraceptive pill
Menopause
Who gets screened for cervical cancer?
Women aged 25-64 years
How often are cervical smears done?
If aged 25 - 49 - every 3 years
If aged 50 - 64 - every 5 years
What happens in a cervical smear?
Liquid based cytology (LBC)
Test for high risk HPV
If positive; triage with cytology
If have had a hysterectomy, do they need a smear?
No, as do not have a cervix
What tests are done in a cervical cytology sample if HPV +ve?
microscopic assessment of cells scraped from the transformation zone
Looks for abnormal cells (dyskaryosis)
Indicate that women has cervical intraepithelial neoplasia (CIN)
Two components of the cervical canal
Endocervix = columnar epithelium Ectocervix = squamous epithelium
What is the transition zone of the cervix especially vulnerable to?
Infection e.g. HPV
Another name for the transformation zone?
Squamo-columnar junction
Name of abnormal cytological cells of the cervix
Dyskaryosis
Nuclear features of dyskaryosis
Increased size and nuclear:cytoplasmic ratio
Variation in size, shape and outline
Coarse irregular chromatin
nucleoli
What do koilocytes reflect?
HPV infection
What happens after HrHPV infection?
Negative for HrHPV = routine recall 3 or 5 years
Postive for HrHPV
- cytology normal; repeat test 1 year
- dyskaryosis; refer to colposcopy
What is a colposcopy?
Further investigation of an abnormal smear - magnification and light to see the cervix
What does acetic acid (+/- lodene) in colposcopy do?
Identify limits of lesion
Select biopsy site
Define area to treat
HPV related pathologies changes to the transformation zone of the cervix
- HPV infection
- Pre-cancerous changes cervical intraepithelial neoplasia (CIN)
- Cervical carincoma
As the host cell infected with HPV matures, what different viral genes are expressed?
E7 protein product = prevents cell cycle arrest
E6 protein product = inhibits cell death
Koilocytos histology
Cells with wrinkled nucleus and perinuclear halo
Multinucleation
Low risk types of HPV
6, 11, 42, 44
What do low risk types of HPV cause?
Genital warts
Low grade CIN
Do low risk types of HPV resolve?
Yes, they are often transient and resolve
High grade risk types of HPV
16, 18, 31, 45
What do high risk types of HPV cause?
Persistent infection increasing risk of developing high grade CIN and (more rarely) cancer
Can you see cervical intraepithelial neoplasia (CIN)?
No, it is invisible to the naked eye
Disorganised proliferation of abnormal cells in squamous epithelium (dysplasia) seen on histology as….
Lack of maturation Variation in cellular size and shape Nuclear enlargement Irregularity Hyperchromasia Cellular disarray
CIN stages and their dysplasia and related regression
CIN1 - low grade dysplasia - will regress
CIN2 - moderate dysplasia - may regress
CIN3 - severe dysplasia - unlikely to regress
Treatment of CIN
LLET2
Thermal coagulation
Laser ablation (uncommon now)
Residual disease of treated CIN would happen in how long?
within 2 years
Recurrent disease of CIN turning into invasive cancer occurs how often?
5% after 3-5 years
Follow up after treatment of CIN
Follow up LBC after 6 months for cytology and high risk HPV
- both negative = return to recall
- both positive = return to colposcopy
Does cervical screening reduce the rate of cervical cancer?
Yes
Peak age of cervical cancer
45-55 years
Risk factors for cervical cancer
HPV related (16 and 18) Multiple partners Early age at first intercourse Older age of partner Cigarette smoking Low socioeconomic status High parity
Types of tumour cells of cervical cancer
Majority squamous carcinoma (80%)
Adenocarcinoma (endocervical) - rising in incidence
Symptoms of cervical cancer
Abnormal vaginal bleeding Post coital bleeding Intermenstrual bleeding Post menopausal bleeding Discharge Pain Weight loss
Investigations of cervical cancer
Clinical
Screening
Biopsy
Staging investigations for cervical cancer
Examination under anaesthetic (especially rectal)
PET-CT
MRI
Aim of cervical screening
To detect PRE-CANCEROUS disease, NOT CANCER
Stages of cervical cancer
Stage 1A - invasive cancer only identified microscopically Stage 1B - clincial tumours confined to the cervix Stage 2 - 4 - cancer has spread - 2 = upper 2/3rds of vagina - 3 = lower vagina, pelvis - 4 = bladder, rectum
Spread of cervical cancer by lymphatic spread goes to …..
Pelvic nodes
Spread of cervical cancer by haematogenous spread to….
liver
lungs
bones
Treatment of cervical cancer
Stage IA; type 3 excision of cervical TZ/hysterectomy
Stage IB-2A; radical hysterectomy or chemoradiotherapy
Stage 2B-4; chemo-radiotherapy
Caesium insertion (24 hours)
Is cervical cancer sensitive to radiation?
Yes, very
What is a caesium insertion?
Type of internal radiotherapy treatment which is used for treating cancers of the cervix, uterus or vagina
Gives high dose of radiotherapy to tumours but gives a low dose to the normal tumours
When should a woman wait post partum for her routine cervical smear?
12 weeks post partum (unless previous abnormal smear)
Women with stage IA cervical cancer can be considered for what treatment if they wish to maintain their fertility?
Cone biopsy with negative margins
