HUMAN PAPILLOMAVIRUS INFECTION

Transcription

1 HUMAN PAPILLOMAVIRUS INFECTION

2 Virological aspects DNA virus with doublestranded circular genome (ca base-pairs) Late-proteins (L1, L2) make up the viral capsid 6 early (functional) proteins (replication, transcription and release of viral particles) 2

3 Phylogenetic classification 3

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5 Epidemiology Common viral infection of the reproductive tract % of all sexually active adults go through an HPV infection sometime Peak incidence at around years of age (correlates with sexual debut) Point prevalence: 10% bis 50% (depending on the study region, the test method etc) 5

6 Annual incidence of invasive anal cancer (US) HPV-ASSOZIIERTE KARZINOME Estimates from IARC 6

7 Gender-neutral vaccination 7

8 Conceptual model of HPV infection leading to cancer

9 HPV-Replikation und Pathogenese 9

10 Transformation/oncogenesis Integration of viral genome with the host genome Total or partial loss of the regulatory E2 protein Deregulated expression of E6 and E7 proteins (oncoproteins) 10

11 Low level immune response to HPV infection Low profile replication in the early phase Replication coupled with cellular differentiation No lysis, viral release coupled with desquamation of the upper epithelial cells No viremia M Stanley 2006 (vaccine) 11

12 Immune response to HPV natural infection versus HPV vaccination Antibody avidity one year after HPV infection and vaccination. Antibody avidity (%) for HPV16 (A) and HPV18 (B) of HPV- specific single-seropositive and multi-seropositive naturally derived antibodies and HPV vaccine-derived antibodies are shown. The dark grey line indicates the mean antibody avidity. *** p< Scherpenisse M 2013 (PLOS One) 12

13 HPV vaccine 13

14 Cervarix vs Gardasil-9 Cervarix showed higher immunogenicity Better cross-protection through Cervarix 14

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16 Mechanism of action 16

17 HPV success stories 17

18 An example from Australia Government-funded vaccine program initiated 2007 with Gardasil Initially girls between 12 and 13 Since 2013: also boys same age School-based vaccination program 18

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20 HPV DNA prevalence pre and post vaccine (6 years after the initiation of the HPV vaccination programme) 20

21 Lower prevalence of vaccine-targeted types in unvaccinated women 21

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23 Impact in Australia Cervical high-grade abnormalities (HGA) % p= Start of vaccination programme (mid-2007) 2010 A relative reduction of ~50% was observed in this age group, post vaccination vs. pre vaccination, barely 3 years after the introduction and the trend continues¹ 1. Brotherton J et al. Lancet

24 Impferfolg in Österreich? Wo sind wir? 24

25 HPV vaccination in Austria A free-of-charge school-based programme since the autumn of 2014 Gender-neutral from the onset 4th grade elementary school children 25

26 Lack of data on HPV prevalence in the prevaccine era in Austria 26

27 HPV prevalence among HG CIN HERACLES Study (HPV Epidemiology Research Applied to Cervical Lesions: a European Study) Tjalma W et al

28 Aged : years Annual screening 28

29 Study partners Dr. Peter Mayr (Kufstein) Dr. Elisabeth Marth Innsbruck Dr. Norman Ruth (Kitzbühl) Dr. Karl-Heinz Kraxner Landeck Dr. Jörg Meier (Imst) 29

30 Discrepant distribution of invasive cervical cancer in tyrolean districts (based on data from ) Incidence Mortality 30

31 Any type: 21,2% 31

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34 Aim of the survey To identify factors associated with HPV vaccine acceptance/refusal 34

35 Study method Cross-sectional study, spring elementary schools The questionnaire: anonymized, self-administered Sociodemographic factors Level of awareness on HPV infection and vaccine HPV immunization status Reasons for refusal of the vaccine 35

36 Table 2. Data on HPV infection and vaccination status (n=439) Characteristics n (%) Heard about HPV 380 (85.4) HPV causes cancer, n (%) Only in women 106 (23.8) Only in men 0 Men and women 297 (66.7) HPV causes no cancer 22 (4.9) HPV in the family 66 (14.8) Source of HPV vaccine information Child s school 415 (93.3) GP/paediatrician 145 (32.6) Vaccine eligible children (n=449) Vaccine eligible boys 195 (41.7) Vaccine eligible girls 254 (57.9) Vaccinated children*, (n=251) Vaccinated boys 101(51.8) Vaccinated girls 150 (59) *erste Dosis (Herbst 2015) 36

37 Factors associated with parents decision to have child receive vaccine Odds ratio (95% CI) Factors Overall Girls (n=254) Boys (n=195) Respondents age (years) > ( ) 1.11 ( ) 0.92 ( ) Number of Children One or two Three or more 0.95 ( ) 0.62 ( ) 1.50 ( ) Marital status Single/divorced Married/partnership 0.89 ( ) 0.99 ( ) 0.69 ( ) Educational status Basic/vocation school High school and above 1.25 ( ) 1.37 ( ) 1.20 ( ) Educ. status (partner) Basic/vocation school High school and above 1.75 ( ) 1.31 ( ) 2.45 ( ) Employment status Non-employed Employed/own business 1.21 ( ) 1.62 ( ) 0.90 ( ) Empl. Status (partner) Non-employed Employed/own business 1.43 ( ) 1.71 ( ) 1.18 ( ) Immigration status Non-immigrant Immigrant 0.57 ( ) 0.83 ( ) 0.91( ) 37

38 Factors associated with parents decision to have child receive vaccine Odds ratio (95% CI) Factors Vaccinated for other school-based vaccines Overall Girls (n=254) Boys (n=195) No yes 15.8 ( ) 15.5 ( ) 18.5 ( ) Heard of HPV No yes 1.74( ) 1.79( ) 1.45 ( ) Respondent s estmation of HPV prevalence HPV infection is rare HPV infection is common 1.80( ) 1.71 ( ) 1.69 ( ) Family history of HPV related diseases No Yes 1.73( ) 1.40 ( ) 2.20 ( ) 38

39 Main reasons for NOT having child receive HPV vaccine (n=185) Reasons, n (%) Fear of debilitating/permanent side effects 56 (30.2) Child too young for the vaccine 54 (29.2) Fear of side effects although temporary 49 (26.5) Not being adequately informed 42 (22.7) Discouraging information about the vaccine from internet 40 (21.6) Generally against all vaccines 37 (20) Other reasons /Vaccine too new (majority) 33 (17.8) The vaccine is just a publicity ploy by pharmaceutical 31(16.8) company Child missed school at the day of vaccination 18 (9.7) Vaccine unnecessary due to low disease risk 18 (9.7) Vaccine not effective 15 (8.1) Child is afraid of needles 14 (7.6) Wait for vaccine which covers more HPV types 12 (6.5) Child afraid of getting vaccinated at school 12 (6.5) Child has allergy 11(5.9) GP/Pediatrician does not believe it is necessary 10 (5.4) 39

40 (Voralberg, Tirol and Salzburg) 40

41 MSM main mode of transmission of HIV infection in Austria (Austrian HIV/AIDS cohort study) 41

42 Significantly higher risk of anal cancer incidence among HIV positive MSM (as compared to women and hetrosexual men) Annual incidence of invasive anal cancer (Data from USA) 42

43 Prevalence (95% CI) of HPV infection among healthy (n= 522) women and HIV positive MSM (n=277) * * * * * * * * * * * * * * * * * * * Cervical samples (healthy women) * Anal samples (HIV positive MSM)

44 Frequency (n) Disparity in the distribution of HPV genotypes between HIV positive MSM and screening women HIV positive MSM (n=263) Screening women (n=522) 44

45 Prevalence of HPV Infection by demographic and behavioural characteristics among HIV positive MSM (n=286) Variables Variable categories Any HPV type (n=238) OR (95% CI) HrHPV (n=73) OR (95% CI) mhpv (n=200) OR (95% CI) Age <45 years (n=148) 45 years (n=129) ( ) ( ) ( ) Marital status Married/Partnershaft (n=106) Single/divorced (n=146) ( ) ( ) ( ) Educational status High school and more (n=142) Basic schooling (n=111) ( ) ( ) ( ) Smoking non-smoker(n=133) smoker (n=133) ( ) ( ) ( ) Age at first sexual contact <16 years (n=100) 16 years (n=74) ( ) ( ) ( ) LSP <10 (n=63) 10 (n=118) ( ) ( ) ( ) BMI= body mass index, LSP= number of life time sexual partners p-value =statistically significant 45

46 No significant association between HIV progression markers (CD+4 count,viral load) and HPV prevalence Good control of HIV Progression markers (n=286) Viral load n (%) detectable 252 (88.1) undetected 18 (6.3) Current CD4+count Mean (SD) 709 (317) Median (IQR) 668 ( ) Lowest ever CD4+ count Mean (SD) 298 (191) Median (IQR) 290 ( )

47 Conclusion HPV is a common infection with a non-negligible global public health consequences Prevention is best achieved through immunisation prior to sexual debut Barrier-free vaccine-access to men/boys and particularly to non-immunized MSM (HIV positive or negative) Work needed on increasing public awareness on the safety of HPV vaccine (particulrly through frontline physicians) 47

48 Thank you! 48

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50 Distribution of invasive cervical cancer in tyrolean districts (based on data from ) 50

51 From: Human papillomavirus-related oropharyngeal cancer Ann Oncol. 2017;28(10): doi: /annonc/mdx304 Ann Oncol The Author Published by Oxford University Press on behalf of the European Society for Medical O All rights reserved. For Permissions, please journals.permissions@oup.com.