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Highlights of the congress

Highlights of the congress. L. Ameryckx. EUROGIN 2007: conclusions ROADMAP on cervical cancer prevention. Age of HPV vaccination: 9 to 14: YES - collectively Up to 18: YES - if resources allow collectively 15 to 26: POSSIBLE on an individual basis > 26: NO current support

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Highlights of the congress

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  1. Highlights of the congress L. Ameryckx

  2. EUROGIN 2007: conclusions ROADMAP on cervical cancer prevention • Age of HPV vaccination: • 9 to 14: YES - collectively • Up to 18: YES - if resources allow collectively • 15 to 26: POSSIBLE on an individual basis • > 26: NO current support sexual activity is NOT a criterion that is easy to use in setting public health policies

  3. Prior exposure by age group to HPV 16/18

  4. Efficacy in seropositive women • Cervarix phase III trial • 16612 women • Seropositive or seronegative for HPV 16/18 • DNA PCR negative • Nl/low grade pap • Efficacy against CIN2+ • Results: 91% effective • Regardless of exposure prior to vaccination; there is still a high level of protection against CIN2+

  5. EUROGIN 2007: conclusions ROADMAP on cervical cancer prevention • Is viral status needed before vaccination? • NO Not under any circumstance with any currently available method • Screening following HPV vaccination? • Continue now • PROBABLY WILL BE MODIFIED

  6. Screening in a vaccinated population • Cytology: PPV will  (~  lesion prevalence) • HPV test: unlikely to be as effected • Recommended: • HPV test • Pap cytology triage • Problem: cost: BUT longer screening intervals • Benefits: self test  workforce cytology detection glandular lesions monitoring vaccine protection

  7. Screening in a vaccinated population • Research: • Cost effectiveness • Age of 1st screening • Screening interval? • RCT!!

  8. EUROGIN 2007: conclusions ROADMAP on cervical cancer prevention • Monitoring HPV vaccination: • Collectively by public health authorities • Different in developed & developing countries • Monitoring is necessary but should not prevent vaccine introduction

  9. Cross-protection against CIN/AIS caused by non vaccine types? • First analysis FUTURE I/II study group: Gardasil • HPV naïve population, nl pap test • > 20000 women aged 16-26 • Follow up: 4 years • Results: • vaccination reduced combined incidence of HPV 31/33/35/39/45/51/52/56/58/59-related CIN2/3 & AIS by 38% • especiallydisease related to HPV 31/45: 62 % • Cross neutralising antibodies to HPV 31/45 have beendemonstrated

  10. Cross-protection against CIN/AIS caused by non vaccine types? • Phase IIb RCT: Cervarix • Infection with HPV 45  by 90 % • HPV 31  by 50%

  11. Cross-protection against CIN/AIS caused by non vaccine types? • Some level of cross protection against infection and infection related disease • Especially to HPV 31/45 • Results = promising • ?? Duration of protection • Priority = second generation vaccines that cover the other oncogenic HPV types

  12. Molecular markers • Cytology: poor sensitivity high FPR: 8.7 % • HPV-test: high sensitivity increase FPR • Histopathology: over- underdiagnosis CIN2+ • Need new markers to overcome limitations

  13. Molecular markers:p16 • ASCUS/LSIL : HPV test • BUT: LSIL: 83% = HPV-HR + only 25%  CIN 2/3 ? Which lesions will persist, progress, regress?

  14. Molecular markers: • HPVexpr E6/E7 neoplastic progression • E6  p53 • E7  pRb  overexpr p16  cell proliferation • HPV E6/E7 m-RNA • P16-INK4A antigen •  expr ~ risk of progression LSIL/ASCUS •  expr ~ CIN 2/3

  15. Molecular markers:p16 • Immunohistochemistry on cytology/biopsy • Overall sensitivity for CIN 2+ : 96% specificity : 83% ASCUS sensitivity : 95% specificity : 84% LSIL sensitivity : 100% specificity : 81%

  16. STOP presentatie

  17. EUROGIN 2007: conclusions ROADMAP on cervical cancer prevention • Age of vaccination • Is viral status needed before vaccination? • Screening following HPV vaccination • Monitoring HPV vaccination

  18. Age and vaccination • Prim target: girls prior to sexual contact:9-12y • Catch up vaccination till age 26? • Older women?

  19. HPV vaccines: unresolved issues • How long will protection last? • Is there any therapeutic efficacy? • Will virus type replacement occur in an immune population? • Will the vaccine viruses mutate? • How will we redesign our screening programs? • Should women who had Rx be offered vaccination? • Is it cost effective to immunise men?

  20. HPV vaccines: unresolved issues • Protection against other HPV related cancers? • Pregnant mothers with HPV associated disease? • Will vaccination reduce HIV transmission? • Effectivity in immunosuppressed patients? • Combination with other vaccines? • Can we immunise young children? • How can we make the vaccines available in the developing world? • How can we introduce new genotypes in future vaccines?

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