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41768
Cancer diagnosis: is it a tumour?
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Cancer Biology Mapa Mental sobre Cancer diagnosis: is it a tumour?, criado por maisie_oj em 09-04-2013.
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cancer biology
cancer biology
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maisie_oj
, atualizado more than 1 year ago
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maisie_oj
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Cancer diagnosis: is it a tumour?
Screening
... In the UK
Only done when... (criterea)
Condition is an important health problem, well understood disease, recognisable at an early stage treatment is more effective at early stages...
Suitable/acceptable tests exist, facilities exist to cope with abnormalitites detected...
Resources exist to allow for multiple/repeated screens at age of risk and the harms and costs are outweighed by the benefits
Screens
Cervical
Well defined disease progression (Normal, CIN I, CIN II and CIN III)
Women aged 25-6yrs
25-49yrs (highest risk) = every 3yrs
50-64yrs (lower risk) = every 5yrs
>65yrs - not screened unless they havn't been screened since 50yrs or abnormal smear seen
If 80% of the population screened then there would be a 95%reduction in the death rate from cervical cancer
"Jade Goody" effect
33,000 more smears than expected, 35% during the month of her death
The biggest increase seen in 25-29yrs age range
Now this surge in women being screened is already trailing off
A negative screen can provide 41-69% protection in women aged 20-54yrs and 73% protection in >55yrs
... with 3-yearly intervals between screens
Protection drops with 5-yearly intervals
Two techniques...
(Classical) 'Pap' smear
Spatula scrapes cells from the surface of the cervix
Must ensure to swab the 'transition zone' (where most neoplasms occur)
= the border between the stratified squamous epithelium of the cervix and the columnar mucous epithelium of the vagina
Swab spread onto glass slide and observed (microscopy)
(Newer) Liquid-based cytology
Same swab taken as in the 'pap' smear
Swab tip is broken off into a solution of preservative
This is spun to remove debris and other obstructive material (mucous etc.)
Automated machine removes the cells and spreads a thin layer onto a glass slide
Slide observed under microscope
HPV and cervical cancer
Epidemiological studies indicate cervical cancer as an STD
HPV found in 85% of cervical carcinomas
High risk forms (= 16, 18, 31, 33, 35, 55 - found in ~100% of invasive cervical carcinomas) and low risk forms (= 6 and 11 - cause genital warts only)
HPV also involved in; anus, penile, vulval, throat and mouth cancers too
Pathogenesis and carcinogenesis
Sexual contact -> HPV exposure
Cervical transmformation zone (infection)
Integration of viral DNA into host DNA
HPV proteins E6 (inhibits p53) and E7 (inhibits; p53, p21 and Rb) - cause avoidance of apoptosis and premature entry into S-phase
Squamous / endocervical columnar differentiation
High/low grade squamous intraepithelial lesions / glandular intraepithelial lesions
Carcinogenic risk factors; smoking, oral contraceptives, high parity (given birth many times), altered immune status, gene mutations, time
Invasive; squamous carcinoma / adenocarcinoma
75% of population exposed to HPV (only 50% to high risk HPV)
of these - 10% have persistent CIN (cervical intraepithelial neoplaisa)
1.3% progress to invasive carcinoma
0.4% die
HPV vaccination
Started in (sept) 2008; offered to all 12-13 and 17-18yo females
x3 injections over 6 (or 12) months
Two vaccines
Cervarix (protects against HPV 16 and 18)
Gardasil (protects against HPV 6 AND 11)
Unanswered questions
How long does protection last?
Is there cross-protection (from other serotypes)?
Will other types of HPV become carcinogenic?
In US 62.5% of males are HPV positive
Need to vaccinate boys?
High risk HPV found in ~100% of invasive cervical carcinomas
Screen for these HPV's by PCR?
Breast
Based on mammography - aimed at detecting calcification
Calcification associated with ductal carcinoma in situ (DCIS)
Pre-invasive
No metastatic capacity
Curable
NHS breast screening programme (BSP): invites women 50-70yrs (highest risk)
screened every 3 years
Is this too long?
Saves 1400 lives per year in England
Is 50yrs the right age?
Now inviting women at 47yrs
Is this screening necessary?
BBC health news - reports a third of breast cancer as being 'harmless'
An independent review, published in the Lancet (2012) - highlights the problem of overdiagnosing cancer
This is the detection of a cancer that would not otherwise cause that person a problem during their lifetime
Waste of time/resources?
Unecessary treatment and follow up to the individual?
Further screening, biopsies - unecessary pain/stress?
The future of breast screening
It is unlikely that breast cancer screening will stop
Instead aim is to target high risk individuals - family history / high mammographic density
Clinical trial in discussion: 'watch and wait' method for DCIS
Once imaging done - biopsy
Fine needle aspirate (sample fluid around mass)
Core needle (removes a 'core' of mass)
Vaccum (removes a larger sample of mass)
Large core biopsy (larger core - may also remove healthy tissue)
Surigical (entire mass cut out under anaesthetics)
Bowel
1 in 20 people develop colorectal cancer (3rd most common cancer in UK and 2nd leading cause of death (after lung))
Screening aimed at detecting the non-malignant polyps (adenomas) - usually present early as blood in stool
Based on faecal occult blood (FOB) testing
Who?: men and women 50-69yrs
When?: every 2yrs
Results: 98% have normal result
2% have positive FOB
Invited for colonoscopy
50% of these - normal
40% of these - adenoma
10% of these - carcinoma (mostly early stage)
Risk: 1/1500 chance in bowel perforation
Currently no screen for...
Ovarian
In 2008... 6,500 cases; 4,400 deaths
5th most common cancer in women (lifetime risk = 1 in 54)
Accounts for 6% of deaths from cancer in women (more then any other gynae cancer in women)
No current test specific enough
Two tests being trialled
CA125
Circulating tumour marker
Raised in 85% of ovarian cancer cases
Raised in 50% in early stages of ovarian cancer
Other causes can raise this marker
Trans-vaginal ultrasound
Ultrasound probe is inserted into the vagina and imaging of the deeper reproductive organs possible through the vaginal wall
Being used in a screening trial (UKCTOCS - UK collaborative trial of ovarian cancer screening)
Screening of general female population 50-74yrs
Women selected at random from GP lists and invited
To date 10,000 post-menopausal women screened
Detected 58 cancers
Missed 12 cancers (6 of these were early stage)
Group 1 - annual CA125 measure if abnormal U/S
Group 2 - annual U/S, if abnormal CA125
Group 3 - No screening
Prostate
No screening programme - but a risk management programme
Based on advice to take up Prostate-specific antigen (PSA) testing
PSA gives a lot of false negatives
10% of all men 50-65yrs will have raised PSA
Only 25% of these will have prostate cancer
Next step: trans-rectal ultrasound (U/S) and biopsyn under prophylactic antibiotics
Positive result: treatment is by radical prostatectomy or radical radiotherapy
Prostate cancer is highly hetergenous (differs massively between individual)
Therefore no evidence that early treatment improves survival
More men die with - rather than from - prostate cancer
Other screening techniques?
Microarrays
Gavaert, 2009
Used microarrays to identify gene clusters associated with tissue specific primary tumours and their metastases
Recognised; breast, colon, lung, ovarian, prostate, kidney and thyroid/kidney clusters of gene expression in epithelial cancers
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