HPV Infections in children & ado’s

1. HPV Infections in children & ado’s What are children? What are ado’s?

2. HPV epidemiology and infections in childhood • Etiology • Perinatal • Sexual abuse • Hetero or auto inoculation • Fomites • Clinic • 1-4 months old babies (from HPV positive mothers) are 50-70% HPV positive • Oropharynx- JORRP • Genital condylomata • Lichen sclerosus

3. Genital warts in childhood What do they mean? • Sexual transmission? • If abuse: 3.4 % - 33% positive HPV • If abuse: 0.3 % - 2% genital warts • But abuse is no must 2) Perinatal transmission? • Intrapartu • Placenta & trophoblast • Amniocentesis • Anal condylomata • Umbilical cord

4. Genital warts in childhood 3) Auto-hetero inocculation • Non genital warts in the genital region • HPV types 2-27-57 in skin lesions 4) Fomites • Clinical impact?

5. Genital warts in children • Management • Multidisciplinary & non judgmental • Anamnesis (child & family) • Trauma? • Physical examination (SOA?) • Behavior? • Judicial authorities • Emotional & psychological support with positive reassurance • Follow-up & risk evaluation

7. HPV epidemiology and infections in adolescents • 13-38 % HPV infected between 12 & 20 years old • 15% currently • 40% abnormal cytology • 1% genital warts • Ado’s are very susceptible to viral infections, just as their videogames • HPV is the most frequent SOA

8. GENITAL: Spiked Vaginal Condyloma

9. 800 Males 700 Females 600 500 400 Rate per 100,000 population 300 200 100 0 13–15 16–19 20–24 25–34 35–44 45–64 65+ Age (years) HPV infections: Kids & Ado’sGenital warts – Age specific incidence (European data) • The highest incidence of genital warts is in people aged 16 to 24 years1 • The high incidence observed in females aged 16 to 19 years may reflect the age of sexual debut2 and their selection of male partner (typically older) 1. PHLS. CDR Weekly 2001;11(35). 2. Bozon M. A quel âge les femmes et les hommes commencent-ils leur vie sexuelle? Comparaisons mondiales et évolutions récentes. Population et Sociétés 2003;391:1–4.

10. 700 7 Males 600 6 Females 500 5 400 4 Rate per 100,000 person years 300 3 200 2 100 1 0 <10 10–14 15–19 20–24 25–29 30–34 35–39 40–44 45–49 50–54 55–59 60–64 >65 Age (years) HPV infections: Kids & Ado’sGenital warts – Age specific prevalence (US data) • The highest prevalence of genital warts is in men and women aged 20 to 29 years Adapted from Insinga RP, Dasback EJ and Myers ER. The health and economic burden of genital warts in a set of private of health plans in the United States. Clin Infect Dis 2003;36:1397–1403.

11. HPV infections: Kids & Ado’s Incidence of genital warts in the UK (1993–2002)* 800 700 • In the UK, the incidence of genital warts is increasing in both males and females 600 Males (16–19 years) 500 Males (20–24 years) Females (16–19 years) Rate per 100,000 population 400 Females (20–24 years) 300 200 100 0 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 Year *1995 data not available for Northern Ireland, 2001 and 2002 data not available for Scotland. Graph: PHLS. CDR Weekly 2003;13(44)

12. HPV infections: Kids & Ado’s • HPV infection: evaluation & management • Sex & abuse? • Number of partners? • Age partners? • Tobacco use? • Condoms? • Immunosupression? • Biological factors? • Demography?

13. HPV infections: Kids & Ado’s • HPV infection: evaluation & management • Sex & abuse? • Number of partners? • Age partners? • Tobacco use? • Condoms? • Immunosupression? • Biological factors? • Demography?

14. Sexual activity and age Q: Is your (12 to 18-year-old) daughter sexually active? + Exactly how old is/are your 12 to18 year old daughter(s)? N = 497 Filter: none

16. Number of partners linked to age Q: With how many partners have you had sexual relations? N = 810 Filter: only women 15-26 who had sexual relations in the past Mean

17. HPV infections: Kids & Ado’s • HPV infection: evaluation & management • Sex & abuse? • Number of partners? • Age partners? • Tobacco use? • Condoms? • Immunosupression? • Biological factors? • Demography?

18. APPENDIX

19. Management of HPV in Kids & Ado’s Current therapies for genital warts • Antiproliferative agents • Podophyllin • Podophyllotoxin (1st line) over 8 weeks cure rate = 70- 80 % • 5 FU • Cidofovir Active on cellular factors involved in HPV replication

20. Management of HPV in Kids & Ado’s • Destructive / excision therapies • Cryotherapy (multiple sessions) • Excision: scalpel – curette – electrosurgery – laser • Local or general anesthesia

21. Management of HPV in Kids & Ado’s • Immunomodulators / therapeutic vaccines • Imiquimod macrophage (cytokine production stimulator) after 4 – 12 weeks: 60-77% result → expensive but useful • Vaccine therapy in animal models are promising

22. Juvenile onset recurrent respiratory papillomatosis (JORRP) Juvenile onset recurrent respiratory papillomatosis 1. Kosko JR and Derkay CS. Role of cesarean section in prevention of recurrent respiratory papillomatosis – Is there one? Int J Pediatr Otorhinolaryngol 1996;35:31–38.

23. Management of JORRP • Cause of respiratory papillomatosis • Rare condition • Most common in the larynx • JORPP (juvenile onset < 4 years) • AORPP (adult onset peak : 21 – 30 years) • Hoarseness of voice & respiratory obstruction • Surgery frequency is highest in children • Complications: • Spread in trachea & bronchi • Malignant conversion • Increase after tracheotomy

24. Management of JORRP • Respiratory papillomatosis • Rarely fatal • Burden on patients & family • Is 100 % due to HPV 6/11 • HPV11 more malignant conversion • JORPP transmission from mother to child during birth • Mothers with active condyloma child : risk < 1 % • AORPP: sexual & non sexual contact with infected lesion • Caesarean delivery might protect but probably not completely • Resection & Adjuvant therapy • Cidofovir injection • Alfainterferon therapy • Intralesional mumps vaccine • Therapeutic HSP-E7 vaccine

25. HPV Infections & VLP’s Ian Frazer, Australia , 1992

26. The strongest defense against a common form of sexual transmitted disease now better than ever is prevention

27. Prevention of HPV • Reduce risk factors • Vaccination strategy : • HPV types multiple (> 200) • No HPV vaccination protects against all types • But: partial cross protection is confirmed • Target group: preteens (girls? boys?)

28. Cervical cancer vaccination is complementary to screening and should start with those who would benefit most Screening 70 PRE-EXPOSURE PEAK EXPOSURE 60 70% life time risk to become infected, often as adolescent or young adult**2-4 50 Proportion of females (new cases) Harbouring Human Papillomavirus (any type) [%]*,1 40 30 20 Cannot screen adolescents 10 0 Age (years) 15-17 20 22 25 30 35 40 45 0 ROUTINE CATCH UP Vaccination 11-15 16-26

29. HPV vaccination strategy “ Do we dream” • Implementation • Sexual activity timing? • Postponing means no lifetime protection? • Urge? • Target group: preteens? Catch-up? • How about parents & culture? • Communication? • High risk population -low income? • Cost/benefit?

30. Sexual activity daughter Q: Is your (12 to 18-year-old) daughter sexually active? N = 401 Filter: only mothers with daughters 12-18

31. Sexual activity daughter Q: Is your (12 to 18-year-old) daughter sexually active? + Exactly how old is/are your 12 to18 year old daughter(s)? N = 401 Filter: only mothers with daughters 12-18

32. HPV vaccination strategy • Europe? • Developed countries? • 3rd world?

33. Recommendation and funding for Human Papillomavirus vaccination are moving forward quickly in most countries Norway Portugal Germany UK Spain Switzerland Belgium Netherlands Finland Ireland France Italy Austria Luxemburg Sweden Denmark Greece NA Recommended Funded Official Planned in 2007 >2007 or uncertain

34. HPV vaccination strategy Pitfalls? • Public & professional education • Cultural • Knowledge • Awareness • Willingness • School projects

35. APPENDIX

36. HPV vaccination strategy 2) Health strategy • Obstetrician/gynecologists • Pediatricians • General physician • Cost benefit • Underdeveloped countries

37. HPV vaccination strategy 3) Myths: Once HPV infected ≠ no indication for vaccination? 4) Long term prevention? Boosters? How long will it take to see results?

38. Physicians in Europe are well aware of * Proportion of awareness of HPV vaccine among physicians according to quantitative study (IPSOS), July 2007

39. Physicians in Europe are willing to vaccinate young girls and women (9-25 years) against cervical cancer Proportion of physicians willing to vaccinate young girls and women (9-25 years) against cervical cancer or to prescribe the vaccine according to quantitative study (IPSOS)

40. Mothers in Europe become aware of cervical cancer vaccination Mothers (of girls aged 9-17 years) Proportion of mothers (of girls aged 9-17 years) aware of the existence of a cervical cancer vaccine according to quantitative study (IPSOS) in selected European countries, July 2007

41. Willingness of mothers to vaccinate daughters Mothers (daughters 9-17)

42. 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 • Is viral status needed before vaccination? • NO - Not under nay circumstance with any currently available method • Screening following HPV vaccination • Continue now and PROPABLY WILL BE MODIFIED • Monitoring HPV vaccines • Not on an individual basis but collectively by public health authorities • Different in developed (record linkage) and delivering countries (sentinel surveys) • Monitoring is necessary but should not prevent vaccine introduction

43. Gardasil & Cervarix