41768
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
- Resources exist to allow for
multiple/repeated screens at age of
risk and the harms and costs are
outweighed by the benefits
- Suitable/acceptable tests
exist, facilities exist to cope
with abnormalitites detected...
- Condition is an important health
problem, well understood
disease, recognisable at an
early stage treatment is more
effective at early stages...
- 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
- The biggest increase seen
in 25-29yrs age range
- 33,000 more smears than expected,
35% during the month of her death
- 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
- Protection drops with 5-yearly intervals
- ... with 3-yearly intervals between screens
- "Jade Goody" effect
- 25-49yrs (highest risk) = every 3yrs
- 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)
- = the border between the stratified
squamous epithelium of the cervix and the
columnar mucous epithelium of the vagina
- Must ensure to swab the 'transition
zone' (where most neoplasms occur)
- Spatula scrapes cells from
the surface of the cervix
- (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
- Slide observed under microscope
- Automated machine removes the cells
and spreads a thin layer onto a glass slide
- This is spun to remove debris and other
obstructive material (mucous etc.)
- Swab tip is broken off into a solution of preservative
- Same swab taken as in the 'pap' smear
- (Classical) 'Pap' smear
- HPV and cervical cancer
- Epidemiological studies
indicate cervical cancer
as an STD
- HPV found in 85% of
cervical carcinomas
- 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
- 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
- Invasive; squamous carcinoma /
adenocarcinoma
- Carcinogenic risk factors; smoking, oral
contraceptives, high parity (given birth many times),
altered immune status, gene mutations, time
- High/low grade squamous intraepithelial lesions
/ glandular intraepithelial lesions
- Squamous / endocervical columnar differentiation
- HPV proteins E6 (inhibits p53) and E7
(inhibits; p53, p21 and Rb) - cause avoidance
of apoptosis and premature entry into S-phase
- Integration of viral DNA into host DNA
- 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
- 0.4% die
- 1.3% progress to invasive carcinoma
- of these - 10% have persistent CIN
(cervical intraepithelial neoplaisa)
- Cervical transmformation zone (infection)
- Sexual contact -> HPV exposure
- 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?
- Will other types of HPV
become carcinogenic?
- How long does protection last?
- Cervarix (protects
against HPV 16 and 18)
- Two vaccines
- x3 injections over 6 (or 12) months
- In US 62.5% of males
are HPV positive
- Need to vaccinate boys?
- Need to vaccinate boys?
- Started in (sept) 2008;
offered to all 12-13 and
17-18yo females
- Epidemiological studies
indicate cervical cancer
as an STD
- High risk HPV found in ~100%
of invasive cervical carcinomas
- Screen for
these HPV's
by PCR?
- Screen for
these HPV's
by PCR?
- Well defined
disease
progression
(Normal, CIN I,
CIN II and CIN III)
- Breast
- Based on mammography -
aimed at detecting calcification
- Calcification associated with ductal carcinoma in situ (DCIS)
- Pre-invasive
- No metastatic capacity
- Curable
- Pre-invasive
- Calcification associated with ductal carcinoma in situ (DCIS)
- NHS breast screening programme (BSP):
invites women 50-70yrs (highest risk)
- screened every 3 years
- Is this too long?
- Is this too long?
- Saves 1400 lives per year in England
- Is 50yrs the right age?
- Now inviting women at 47yrs
- 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?
- Further screening, biopsies
- unecessary pain/stress?
- Waste of time/resources?
- This is the detection of a cancer that
would not otherwise cause that
person a problem during their lifetime
- 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
- It is unlikely that breast cancer screening will stop
- BBC health news - reports a third
of breast cancer as being 'harmless'
- screened every 3 years
- 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)
- Fine needle aspirate
(sample fluid around mass)
- Based on mammography -
aimed at detecting calcification
- 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
- 50% of these - normal
- Invited for colonoscopy
- Based on faecal occult blood (FOB) testing
- 1 in 20 people develop colorectal cancer
(3rd most common cancer in UK and 2nd
leading cause of death (after lung))
- Cervical
- 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)
- 5th most common cancer in
women (lifetime risk = 1 in 54)
- 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
- Circulating tumour marker
- Trans-vaginal ultrasound
- Ultrasound probe is inserted into the vagina and imaging of the
deeper reproductive organs possible through the vaginal wall
- 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)
- Detected 58 cancers
- To date 10,000 post-menopausal women screened
- Group 1 - annual CA125 measure if abnormal U/S
- Group 2 - annual U/S, if abnormal CA125
- Group 3 - No screening
- Women selected at random
from GP lists and invited
- Screening of general female population 50-74yrs
- CA125
- Two tests being trialled
- In 2008... 6,500 cases; 4,400 deaths
- 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
- Therefore no evidence that early
treatment improves survival
- Prostate cancer is highly hetergenous
(differs massively between individual)
- Positive result: treatment is by radical
prostatectomy or radical radiotherapy
- Only 25% of these will have prostate cancer
- 10% of all men 50-65yrs will have raised PSA
- PSA gives a lot of false negatives
- Based on advice to take up
Prostate-specific antigen (PSA) testing
- No screening programme - but a
risk management programme
- Ovarian
- Only done when... (criterea)
- 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
- Recognised; breast, colon, lung, ovarian, prostate, kidney and
thyroid/kidney clusters of gene expression in epithelial cancers
- Used microarrays to identify gene clusters associated
with tissue specific primary tumours and their metastases
- Gavaert, 2009
- Microarrays
- ... In the UK
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