Bioengineering and World HealthOutlineImportance of Early DetectionScreeningHow do we judge efficacy of a screening test?Bioengineering and Cervical CancerStatistics on cervical cancerGlobal Burden of Cervical CancerRisk factorsHuman papilloma virus (HPV)HPV and cervical cancerSlide 12PathophysiologyHPV vaccineHow Do We Detect Early Cervical Cancer?Pap SmearColposcopy and BiopsyColposcopy and TreatmentDetection and TreatmentScreening Guidelines, ACSSlide 21Slide 23New Technologies for Cervical CancerLiquid Based Pap SmearSlide 26Automated Pap Smear ScreeningHPV TestingSlide 29Sensitivity of HPV TestingComparison of Various TechniquesCostsNeedle BiopsySlide 34Slide 35Slide 36Slide 37Summary of CancerSummary of Cervical CancerSlide 40Bioengineering and World HealthLecture ThirteenOutlineThe burden of cancerHow does cancer develop?Why is early detection so important?Strategies for early detectionExample cancers/technologiesCervical cancerOvarian cancerProstate cancerImportance of Early DetectionFive Year Relative Survival RatesScreeningUse of simple tests in a healthy population Goal: Identify individuals who have disease, but do not yet have symptomsShould 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 screeningHow do we judge efficacy of a screening test?Sensitivity/SpecificityPositive/Negative Predictive ValueBioengineering and Cervical CancerStatistics on cervical cancerUS data (2007)Incidence: 11,150Mortality: 3,670World data (2004)Incidence: 510,000 (80% developing world)Mortality288,000 deaths per year worldwideGlobal Burden of Cervical CancerRisk factorsHPV infectionHPV infection is the central causative factor in squamous cell carcinoma of the cervix Sexual behaviors Sex at an early ageMultiple sexual partnersCigarette smokingHuman papilloma virus (HPV)Most common STD>70 subtypesAsymptomatic infections in 5-40% of women of reproductive ageHPV infections are transientHPV and cervical cancerWhat Initiates Transformation?PathophysiologyHPV vaccineVirus-like particles (VLP) made from the L1 protein of HPV 16approved for use in girls and women aged 9 to 26 years in the USnot effective to women already exposed to HPVEffective on 4 HPV isotypesRecombinant technologyAlternative prevention technique to screening?How Do We Detect Early Cervical Cancer?Pap Smear 50,000-300,000 cells/per slideCytotechnologists review slides (<100/day)Se = 62% 3%Sp = 78% $6BColposcopy and Biopsy Se = 95%Sp = 44%ColposcopeBiopsy sectionsColposcopy and TreatmentCIN 1/LGSILCIN 1/LGSILCIN 2/HGSILCIN 2/HGSILCIN 3/HGSILCIN 3/HGSILMicroinvasive CAMicroinvasive CAInvasive CAInvasive CAInvasive CAInvasive CADetection and TreatmentScreening: Pap smearDiagnosis: Colposcopy + biopsyTreatment:Surgery, radiotherapy, chemotherapy5 year survivalLocalized disease: 92% (56% diagnosed at this stage)Screening Guidelines, ACSAll women should begin cervical cancer screening about 3 years after they begin having vaginal intercourse, but no later than when they are 21 years old. Screening should be done every year with the regular Pap test or every 2 years using the newer liquid-based Pap test.Beginning at age 30, women who have had 3 normal Pap test results in a row may get screened every 2 to 3 years with either the conventional (regular) or liquid-based Pap test.Option for women over 30 is to get screened every 3 years with either the conventional or liquid-based Pap test, plus the HPV DNA test.Trends in Screening Cervical CancerChallengeDeveloped and developing worldCost and infrastructure requirements for screeningNeed for appropriate technologiesNew Detection TechnologiesAims:Reduce the false positive and false negative ratesGive instantaneous resultsReduce the costsNew Technologies for Cervical CancerLiquid Based Pap testingAutomated Pap smear screeningHPV TestingVIAHPV VaccineLiquid Based Pap SmearRinse collection device in preservative fluid Process suspension of cells to deposit a monolayer of cells on a microscope slide Conventional PapLiquid Based Paphttp://www.prlnet.com/ThinPrep.htmLiquid 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 slideAutomated Pap Smear ScreeningTriPath Care Technologieshttp://www.tripathimaging.com/usproducts/index.htmhttp://www.tripathimaging.com/images/cutaway.gifHPV TestingThe DNAwithPap Test is FDA-approved for routine adjunctive screening with a Pap test for women age 30 and older. Digenehttp://www.digene.com http://www.digene.com/PapXYLC-5301-30%20VER%20X.mpgNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN NNNNNNNNNNNNNNNNNNNNNNNNNNNNNN NNNNNNNNNNNNNNNNNNNNNNNNNNNNNN NNNNNNNNNNNNNNNNNNNNNNNNNNNNNN NNNNNNNNNNNNNNNNNNNNNNNNNNNNNN N1. Release Nucleic Acids NClinical specimens are combined with a base solution which disrupts the virus or bacteria and releases target DNA. No special specimen preparation is necessary. N2. Hybridize RNA Probe with Target DNA NTarget DNA combines with specific RNA probes creating RNA:DNA hybrids. N3. Capture Hybrids NMultiple RNA:DNA hybrids are captured onto a solid phase coated with universal capture anbtibodies specific for RNA:DNA hybrids. N 4. Label for Detection NCaptured RNA:DNA hybrids are detected with multiple antibodies conjugated to alkaline phosphatase. Resulting signal can be amplified to at least 3000-fold. N5. Detect, Read and Interpret Results NThe 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).Sensitivity of HPV TestingStudy of 5,671 women age >30 years http://www.digene.com/images/sens.gifComparison of Various TechniquesSensitivity SpecificityPap smear 60-80% 45-70%Colposcopy 90-100% 20-50%Digene HPV Test80-90% 57-89%VIA 67-79% 49-86%CostsPap Test
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