Download - lecture12 - Rice University
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BME 301
Lecture Twelve
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Outline
The burden of cancerHow does cancer develop?Why is early detection so important?Strategies for early detectionExample cancers/technologies
Cervical cancerOvarian cancerProstate cancer
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Importance of Early DetectionFive Year Relative Survival Rates
0102030405060708090
100
Local Regional Distant
BreastOvaryCervix
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Screening
Use of simple tests in a healthy population Goal:
Identify individuals who have disease, but do not yet have symptoms
Should be undertaken only when:Effectiveness has been demonstratedResources are sufficient to cover target groupFacilities exist for confirming diagnoses Facilities exist for treatment and follow-up When disease prevalence is high enough to justify effort and costs of screening
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How do we judge efficacy of a screening test?
Sensitivity/SpecificityPositive/Negative Predictive Value
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Global Burden of Cervical Cancer
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Screening Pap SmearEach slide: 50,000-300,000 cellsCytotechnologists review < 100 slides per day10% of "normal" slides re-screened
Se = 62%Sp = 78%False negative smears account for 3% of U.S. Cervical Cancer cases/year http://www.gayfamilyoptions.org/imag
es/hpv3.jpg
http://www.geocities.com/HotSprings/Sauna/2329/image3.jpg
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Detecting Cervical Pre-Cancer
Se = 95%Sp = 44%
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New Technologies for Cervical Cancer
Liquid Based Pap testingAutomated Pap smear screeningHPV TestingVIAHPV Vaccine
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Liquid Based Pap Smear
Rinse collection device in preservative fluid Process suspension of cells to deposit a monolayer of cells on a microscope slide
Conventional Pap Liquid Based Pap
http://www.prlnet.com/ThinPrep.htm
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Liquid Based Pap SmearGentle dispersion breaks up blood, mucous, non-diagnostic debris, and mixes sampleNegative pressure pulse draws fluid through filter to collect a thin, even layer of cellsMonitor flow through filter during collection to prevent cells from being too scant or too dense Cells then transferred to a glass slide
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Automated Pap Smear Screening
TriPath Care Technologieshttp://www.tripathimaging.com/usproducts/index.htm
http://www.tripathimaging.com/images/cutaway.gif
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HPV TestingThe DNAwithPap Test is FDA-approved for routine adjunctive screening with a Pap test for women age 30 and older. Digene
http://www.digene.com
http://www.digene.com/PapXYLC-5301-30%20VER%20X.mpg
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1. Release Nucleic Acids
Clinical specimens are combined with a base solution which disrupts the virus or bacteria and releases target DNA. No special specimen preparation is necessary.
2. Hybridize RNA Probe with Target DNA
Target DNA combines with specific RNA probes creating RNA:DNA hybrids.
3. Capture Hybrids
Multiple RNA:DNA hybrids are captured onto a solid phase coated with universal capture anbtibodies specific for RNA:DNA hybrids.
4. Label for Detection
Captured RNA:DNA hybrids are detected with multiple antibodies conjugated to alkaline phosphatase. Resulting signal can be amplified to at least 3000-fold.
5. Detect, Read and Interpret Results
The bound alkaline phosphatase is detected with a chemiluminescent dioxetane substrate. Upon cleavage by alkaline phosphatase, the substrate produces light that is measured on a luminometer in Relative Light Units (RLUs).
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Sensitivity of HPV Testing
Study of 5,671 women age >30 years http://www.digene.com/images/s
ens.gif
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Comparison of Various Techniques
Sensitivity SpecificityPap smear 60-80% 45-70%
Colposcopy 90-100% 20-50%
Digene HPV Test 80-90% 57-89%
VIA 67-79% 49-86%
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Needle Biopsy
Dichroic Mirror
LED Source
10X UPLAPO Objective
Image Guide
Tube Lens
CCD Camera
Frame Grabber
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Needle Biopsy
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Needle Biopsy
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Summary of Cancer
The burden of cancerContrasts between developed/developing world
How does cancer develop?Cell transformation Angiogenesis Motility
Microinvasion Embolism Extravasation
Why is early detection so important?Treat before cancer develops Prevention
Accuracy of screening/detection testsSe, Sp, PPV, NPV
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Summary of Cervical CancerCervical cancer
2nd Leading cause of cancer death in women in worldCaused by infection with HPVPrecancer cancer sequencePrecancer is very common
Screening & DetectionPap smear; colposcopy + biopsyReduces incidence and mortality of cervical cancerInsufficient resources to screen in developing countries
New technologiesAutomated reading of Pap smears reduce FN rateHPV testingVIA
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0%
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$0 $500 $1,000 $1,500 $2,000 $2,500 $3,000Lifetime Screening Cost
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Cer
vica
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isk
South AfricaScreening 1X/LifeCost saving to <$50/YLS
South AfricaScreening 2X/Life$50-$250/YLS
South AfricaScreening 3X/Life$250-$500/YLS
United StatesPap + HPV Every 3 yrs.
$60,000/YLSUnited States
Pap + HPV Every 2 yrs.$174,000/YLS
United StatesPap + HPV Every Year
$795,000/YLS
15 Weeks
1,000 Years!
Global Inequities in Cancer Prevention
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Assignments Due
Tuesday, October 21Project 6
Thursday, October 23Project 7: Preliminary Project Proposals7 minute presentation, 3 minute Q&A Background, problem definition, design requirements, decision matrix, proposed solutionPlan of action and timeline!