Cytologi, HPV infeksjon og vaksinasjon. Hammerfest

Transkript

1 Cytologi, HPV infeksjon og vaksinasjon Hammerfest OE Iversen Dept. of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway

2 Kasuistikk okt -10 Q 24 år: Frykt for cervixcancer pga familieanamnese. Cyt 20 år gml: N Cyt 23 år: N 24 år: blødningsforstyrrelse. Ville ha ny cyt fastlege avslo skiftet GU: suspekt tumor på cervix Biopsi: Adenocarcinom (I b) Lærdom/Poeng Screening <25 virker dårlig Adenocarcinom oversees Vaksinasjon? Kunne hun fått den?

3 Rate per 100,000 Age-specific incidence With/without screening 120 Age-specific incidence rates of cervical cancer in Brazil and the UK Brazil UK Age Ferlay J et al. Globocan IARC 2004.

4 Early stop of FUTURE I and II Based on recommendations from the Data Safety Monitoring Board, it was decided for ethical reasons to stop the trials early in order to not delay vaccination of the placebo group. December 2005

5 Fra: Kampen mot cervix cancer: Utvikling Observasjon av naturlig forløp via Terapi og Sekundærprofylakse Til: Primærprofylakse HPV vaksinasjon

6 Milepeler i norsk screening Før forts 2013/4??? 2023 Opportunistisk Organisert Organisert + HPV triage HPV primærscreening (Fase IV) Screening av vaksinerte

7 NRK Relativ ja! Absolutt nei!

8 Best? Behandling eller forebygging? Dagbladet

9 Hva er målet med screeningprogrammene? (1995) Cervix 1. Redusere insidens - 2. Redusere dødelighet Mamma Redusere insidens Redusere dødelighet (målbar etter > 10 år) 3. Rasjonell bruk av prøver (ressurser) Nye tiltak (HPV) må dokumentere eller sannsynliggjøre bedret måloppnåelse!! Tidlig vurdering av surrogatmål ( downstaging, tumorstørrelse) Finne de 3000 blant > som må coniseres!

10 HPV - DNA virus Artspesifikk, infiserer plateepitel i hud og slimhinner Predeliksjonssted: transformasjonssonen akl 2004

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12 Bethestad nomenklatur innført i Norge 2005 HPV test

13 HPV related resources - cervix Norway 2005 (pop. 4,5 mill) gynecological exam. and smears controls for abnormal smears (?) biopsies 3000 conizations 300 cx cancers xxxxx exstra pregnancy visits because of conizations xxx extra late abortions and premature deliveries treatments for condylomas

14 Resultater - cytologi ( n= ) HPV triage av ASCUS/LSIL Normal 93,0 % Uegnet 2,5 % ASCUS 2,2 % LSIL 1,4 % HSIL 0,7 % Cancer 0,03 %* * = 3 pr

15 Screening in Norway Quality asurance manual 2005

16 Norwegian Cervical Cancer Screening Program from 1995 Every third year, ages Standardised follow-up routines One cytology form One classification system (Bethesda from 2005) One coding system (SNOMED) One reporting system One national database Mandatory reporting system National advisory group National QA Manual

17 The co-ordinated screening program in Norway from 1995 has resulted in: Fewer Pap-smears (decreased expenses) Increased coverage (80 % years) Decreased incidence of SCC (25-69 years) years: Coverage increased from 43,5 to 67,5% and incidence rate decreased from 30,0 to 15,1

18 Incidence of SCC and ACC

19 Hva er potensialet for cervix cancer screening

20 Regression of LSIL in young women They are a minority, but...

21 Oppfølging av ASCUS + LSIL Vi skal finne de 3000 av > som skal behandles for CIN 2+ Normal Ny cyt om 3 år ASCUS LSIL. HPV test 6 mnd - + HSIL Kolposkopibiopsi.

22 HPV testing brukes til kliniske veivalg Anbefalt fra 3/2005: Gyn.onk Veileder, Kreftregisteret Cytologi uegnet/normal høyrisiko HPV negativ Cytologi om 3 år Uegnet, uavklart og lavgradig cytologi Cytologi HPV-test 6 måneder Cytologi lavgradig/uavklart høyrisiko HPV negativ CIN2/3 behandling Normal/CIN 1 HPV 6 måneder Cytologisk høygradig HPV-test utgår Cytologi lavgradig/uavklart høyrisiko HPV positiv Cytologi uegnet/normal høyrisiko HPV positiv Kolposkopi umiddelbart HPV test 6 måneder Høyrisiko HPV positiv Høyrisiko HPV negativ. Vilkårlig valg av HPV test

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24 IMPLEMENTERINGSSTUDIE I 4 FYLKER: HPV-TEST I PRIMÆRSCREENING MOT LIVMORHALSKREFT 2. desember 2010 Utvalgsmedlemmer: Olav K. Vintermyr Björn Hagmar Mari Nygård Ivar Sønbø Kristiansen Ole-Erik Iversen Bente Kristin Johansen Jannicke Berland Bjørn Hagen Christine M. Jonassen Kari Hilde Juvkam Tore Gutteberg (frem til aug 2010) Sveinung W. Sørbye (fra sep 2010) Trude Andreassen

25 Why do we still have a problem with Invasive Cervical Cancer in countries with organized screening programmes? 60 % of the cancers occur in the 15 % of the women who do not attend the programme!! (Cannot be reached by any screening test, but possibly by Primary prophylaxis) (Norwegian Cancer Registry ) Adenocarcinoma unaffected by Screening Conlusion: Primary prophylaxis better than secondary!

26 And for those who do not attend: self sampling for HPV testing «Quick and simple selfsample kit followed by DNA analysis that detects 13 highrisk strains of HPV. «

27 The Nobel Prize in Physiology or Medicine 2008 Harald zur Haussen "for his discovery of human papilloma viruses causing cervical cancer" October 6th 2008

28 HPV - Main areas of development 1983 Zur Haussen Diagnostics Prophyl. Vaccines Therapeutic Vaccines

29 Number of HPV related papers/5 y (Total ) > 20 fold increase! (The pill: ca 5000 in 50 years) PubMed

30 Cervix cancer by HPV type Munoz N: Int J Cancer 2004;111: Other +X Proportion of cancers associated with HPV types 70.7% 332,

31 Rate per 100,000 Rates of Diagnoses of Genital Warts (U.K.) 300 CDR Weekly 2001; Vol 11(35) Samme for HPV 16/18 ++ som 6/11? 250 Males Females oei 35

32 1. Jansen KU, Shaw AR. Annu Rev Med. 2004;55: Koutsky L. Am J Med. 1997;102: Franco EL, Villa LL, Richardson H, Rohan TE, Ferenczy A. In: Franco EL, Monsonego J, eds. Oxford, UK: Blackwell Science; 1997: Tortolero-Luna G. Hematol Oncol Clin North Am. 1999;13: , x. HPV and Anogenital Warts Images top left and top right: Reprinted with permission from NZ DermNet ( HPV 6 and 11 responsible for >90% of anogenital warts 1 Clinically apparent in ~1% of sexually active US adult population 2 Estimated lifetime risk of developing genital warts ~10% 3,4

33 Stanley M, Lancet Conference: HPV and cancer Nov 12, 2010

34 Chaturvedi A, Lancet Conference: HPV and cancer Nov 12, 2010

35 Lassen P, Lancet Conference: HPV and cancer Nov 12, 2010

36 HPV vaccines - types: First published studies Monovalent (HPV 16) Koutsky NEJM 2002 Bivalent #(HPV 16/18) Harper Lancet 2004/6 Quadrivalent* (6, 11, 16, 18) Villa LL Lancet 2005 Polyvalent (8 and 9) in phase III trials from 2007 * Gardasil # Cervarix

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38 Adult Women (24-45 years) negative to the relevant vaccine HPV type (P 019)

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40 Young men (16-26 years) negative to the relevant Vaccine HPV type (P 026)

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42 Donovan B et al. Lancet Infect Dis 2011, updated with person communication on Real-life of women of impact free vaccine - on eligible genital age warts (GW) ital warts, by resident status, Proportion of women of free vaccine eligible age with new episodes of genital warts, by resident status, p-trend=0.96 p-trend=0.84 Pre-vaccine period p-trend=0.06 p-trend<0.001 Vaccine period -25% -73%

43 Most Frequently Asked Questions about HPV- vaccines Are the vaccines safe and monitored? How long will the protection demonstrated by HPV vaccines last?

44 Post licensure: Health authorities reaffirm the positive safety profile of GARDASIL 1. EMEA statement on the safety of GARDASIL. EMEA/37479/ last accessed on Centers for Disease control website. Available at: last accessed on RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE, No 5, 30 JANVIER Press release Spain MINISTERIO DE SANIDAD Y POLÍTICA SOCIAL

45 Har vi valgt feil kjønn for vaksinasjon? Hva om bare gutter? Ville beskytte jenter Ville beskytte MSM Redusere mannlige HPV cancere Hva med lesbiske? OBS vaksinedekning

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47 Hvor mye HPV vaksine tilbys i Skandinavia? (årskull): Norge: 11/12 år 1 Sverige*: år 14 Danmark: år 14 *+ Blå resept ordning UK: 6 Årskull

48 HPV morbiditet et årskull uvaksinerte kvinner (30.000) 3000 koniseringer (10%) 300 cx cancere (1 %) 100 cx cancer dødsfall XX Ekstra senaborter og premature fødsler 3000 condylomer (10 %)

49 Viktige spørsmål i debatten: Ikke testet på 12-åringer Ikke vist beskyttelse mot kreft Kjenner ikke varighet av vaksinen Andre HPV typer tar over

50 All 12 years old girls to be Research rabbits

51 20 girls died Re HPV vaccine

52 Assault on girls Professor in ethics Would not vaccinate my daughter + Editorial against vaccine Week before budget

53 HPV vaccine for the rich only!

54 Scenario when vaccination started 2009 of all girls at 12 years: cumulative proportion vaccinated Vaccinated cohort starts screening % % vaccinated years % NOT vaccinated years 2023: Vaccinated women needs new HPV based screening algorithm

55 Takk for oppmerksomheten