Hpv vaccination gpsnew

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Lecture for BSCCP series on HPV vaccination

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Hpv vaccination gpsnew

  1. 1. HPV VACCINATION ANDPREVENTION OF CERVICALCANCERGrainne FlannellyNational Maternity Hospital
  2. 2. Setting the sceneHPV and Cervical cancerWhat are the vaccines and what do we know about their use• Facts• AssumptionsNational immunisation programmes – challenges, effectiveness,cost, impact on screening
  3. 3. <3.9 <7.9 <14.0 <23.8 <55.6Cancer of the cervix (mortality/100,000) Mortality falling developed world Mortality rising in developing world
  4. 4. Relative incidence of cervical cancer Irelandversus England024681012141618ESRper100,000womenIrelandEnglandNCRI, NHSCSP (Includes Wales up to 1994)
  5. 5. Human Papilloma VirusThe link with cervical cancerEpidemiology ofcervical cancer–sexually transmittedagent.HumanPapillomavirus(HPV) is the majorinfectious agentinvolved .99.7% of cervicalcancers contain highrisk HPV DNA
  6. 6. Human Papilloma virusThe virology lessonDoublestranded, tightlycoiled, circularvirusMore than 100typesGenetic structure• Early Late and Upperregulatory areas E(1,2,6,7), L (1,2)Infects basal celllayers of genitalepithelium
  7. 7. HPV and cervical neoplasia –Molecular pathwayIntegration of HPVDNA into hostnucleusGatekeeper gene E2Controls Activity ofE6 and E7.Integration damagesE2Interferes with“Quality controlinspectors” or tumoursupressor genes.•E 6 “takes out” p53•E 7 “takes out” pRBResult - Moreabnormal cells whichlive longer
  8. 8. Natural History of HPV infection•Transmission bysex•Lifetime risk 80% -most within 18monthsExposure•Transient•Most resolve within18 monthsInfection•Less than 20%persist•No antibodiesdetectablePersistence•Virus integratesinto host DNAMalignantTransformation •Loss of tumoursupressor gene E2•Uncontrolled cellsdivisionCIN
  9. 9. HPV and neoplasia the problemA largeproportion ofsexually activewomen will beinfected withHPVA minority willhave persistentinfection withhigh grade CINFewer still willevolve intoinvasive cancerThere must be other factors which interfere with immunity ? Cigarette smoking
  10. 10. Which Human Papillomaviruses to target?Low Risk 6, 11, 40, 42, 43, 44, 54, 61Anogenital wartsHigh risk 16, 18 45, 31, 33, 52, 58, 35,59, 56, 39, 51, 73, 68, 66Anogenital neoplasia6,11,16,18,90%warts70%cervicalcancer
  11. 11. HPV Vaccination• Virus Like Particle• L1 Surface protein asempty shell (no DNA)• 5 years years follow up• Immunogenic and safe
  12. 12. Current VLP VaccinesNo comparitive studies300 Euros for three dosesQuadrivalentSanofi PasteurGardesilSubtypes16/18/6/11BivalentGSK Bivalent VaccineCeverixHPV 16/18Not yet Licenced
  13. 13. Future 2 Study: QuadrivalentVaccine•93% of studypopulation were nonvirgins•Efficacy best in groupof women who wereHPV negative at timezero (PPE)•Efficacy reduced inModified Intention totreat group (MIT)(NEJM, May 2007)
  14. 14. Questions efficacy in non HPVNaive womenTarget PercentageReductionHigh Grade CIN/AISassociated withHPV16/1839%High grade CIN/AISassociated with anyCIN12%Condylomata 68.5
  15. 15. HPV Vaccine – Provisional ACIPRecommendations• Routine vaccination of females 11 or 12 years of age• The vaccination series can be started as young as 9 yearsof age at the clinicians discretion• Vaccination is recommended for females 13-26 years of agewho have not been previously vaccinated (Note notMandated)• Ideally vaccine should be administered before onset ofsexual activityCDC, June 2006
  16. 16. UK• NHS• 27th October 2007• JVCI – Advice• Vaccination programme• Girls aged 12-13• Catch up to 18 yearsdelivered over two years
  17. 17. Questions - Epidemiology• What proportion of cervical cancer and other HPVrelated diseases are caused by subtypes covered byvaccines? – (70%)• What fraction of cervical cancer overall will beprevented by a vaccine against HPV 16 and 18? -(Depends on uptake and durability)• Will immunity induced by vaccines alter thedistribution of other non vaccine HPV types? –(Unknown)(Lowndes, 2006)
  18. 18. Questions – Cost and impact on screeningprogramme• How will a vaccination programme affect currentprogrammes for cervical cancer screening and whenshould screening change?• What is the cost effectiveness of various strategies forvaccination programmes?(Lowndes, 2006)
  19. 19. Effect on screeningWhile 70% of cancersare associated withHPV 16/18 a vaccinewith 98%effectiveness mayreduce cancers byonly 51%Replacement withother high riskvaccines an issue• Cervical Screening willhave to continue forvaccinated women• Potential for Targetedscreening based onvirological tests infuture
  20. 20. HPV Vaccine and Cervical CancerScreening• Cervical cancer screening recommendations have NOTchanged for females who receive HPV vaccine• 30% of cervical cancers caused by HPV types notprevented by the quadrivalent HPV vaccine• Vaccinated females could subsequently be infected withnon-vaccine HPV types• Sexually active females could have been infected prior tovaccinationCDC, June 2006
  21. 21. Cost effectiveness – comparison with othervaccinations• Cost 300 euro per person – most expensive vaccine yetbut… cheaper for countries than individualsVaccination Life expectancy increase(days)HPV 2.8Measles 2.7Mumps 3.0Rubella 0.3Pertussis 3.3
  22. 22. EffectivenessCombining vaccination of 12 year old girls with screeningwould reduce cancer by 90% but would cost $45,000 perQALY gainedInclusion of boys would produce marginal increase inefficacy but would increase the cost per QALY gained bya factor of 10 to $450,000
  23. 23. Modelling study FinlandBritish Journal of Cancer (2007) 96, 514 – 518
  24. 24. Catch up vaccinationBritish Journal of Cancer (2007) 96, 514 – 518
  25. 25. Acceptability of the vaccine• Lack of awarenessShock, Fear,• Before education• Acceptors 55%• Decline 22%• Undecided 23%• Following education• Accept 74%• Decline 18%• Undecided 8%Journal of lower genital tract disease 2004;8(3):188-94
  26. 26. Conclusions• Vaccination before sexual debut maximises the long termimpact of vaccination• Catch up programmes can speed up impact and reducethe number of cumulative cases.• Little evidence in favour of vaccinating women whoalready have had HPV

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