Co přinesly 2 roky HPV očkování? Marek Pluta 2. lékařská fakulta Karlovy univerzity Praha Fakultní nemocnice Motol, Praha

Uterine cervix cancer - absolute numbers

PREVENCE RAKOVINY DĚLOŽNÍHO HRDLA HPV infection Převzato a upraveno Franco et al., 2006

Klíčové výsledky studií fáze III HPV vakcín Doba sledování Zahrnuté HPV typy Účinnost na CIN2+ vyvolaných HPV 16 nebo 18 Účinnost HPV 16 CIN 2+ Účinnost HPV 18 CIN 2+ Účinnost HPV 16 or 18 CIN 2 Účinnost HPV 16 or 18 CIN 3 Terapeutická účinnost Účinnost na VIN 2/3, VaIN 2/3 Účinnost na genitální bradavice SILGARD 36 měsíců (advanced) 6, 11, 16, 18 Prokázáno Ne Cervarix 15 měsíců (interim) 16, 18 Prokázáno Dosud neprokázánoa Ne Dosud neprokázáno Nestudováno 1/Bosch/p. 16/ Table 1 aProven in combined analysis of Phase II and III trials. bIn postlicensing evaluation (http://www.who.int/vaccine_safety/en/). cIn clinical trials. dCorresponds to duration of trials in 2007. Reprinted with permission from Bosch FX, Castellsagué X, de Sanjosé S. Br J Cancer. 2008;98:1521.

Očekávané přínosy vakcinace? očekávaný pokles (HPV16/18) desetiletí KDH 73% HSIL 57% roky LSIL 24% We can have an effect not only on cervical cancer but also precancerous lesions – a tremendous impact. ASCUS 19% měsíce

Efficacy Against Any Abnormal Pap Tests Regardless of Causal HPV Type -20 -40 % Reduction 23% (9.4, 34.0) 16% (8.1, 23.5) 35% (8.9, 54.2) 43% (2.9, 66.9) (95% CI) -60 ASC-US HR + LSIL ASC-H HSIL Cases Placebo 359 1000 89 41 Cases Vaccine 285 864 59 24 ASC-US = atypical squamous cells of undetermined significance; LSIL = low-grade squamous intraepithelial lesion; ASC-H = atypical squamous cells, cannot exclude HSIL; HSIL = high-grade squamous intraepithelial lesion Huh WK. Data presented at: Society of Gynecologic Oncologists 39th Annual Meeting on Women’s Cancer™; March 9-12, 2008; Tampa, FL.

Efficacy Against Any Cervical Procedure Regardless of Causal HPV Type -20 -40 22% (13.9, 29.1) 42% (27.7, 53.5) % Reduction (95% CI) -60 Colposcopy with Biopsy Definitive Therapy Cases Placebo 950 230 Cases Vaccine 741 132 Huh WK. Data presented at: Society of Gynecologic Oncologists 39th Annual Meeting on Women’s Cancer™; March 9-12, 2008; Tampa, FL.

Proporce karcinomů asociovaných s HPV typy Cross protektivita 20 40 60 80 100 6.7 2.9 2.6 2.3 2.2 1.4 1.3 1.2 1.0 0.7 0.6 0.5 0.3 4.4 16 +18 +45 +31 +33 +52 +58 +35 +59 +56 +51 +39 +68 +73 +82 +Other +X Proporce karcinomů asociovaných s HPV typy 70.7% 80-82% 80-82% Cervarix™ target As shown in this slide, high-risk (oncogenic) types, HPV 16 and HPV 18* are responsible for approximately 70% of the women worldwide that are diagnosed with cervical cancer1. Among the 2 billion women in the world over the age of 15, there are approximately 470,000 cases of cervical cancer. Within those cases, we estimate that over 330,000 can be prevented with a vaccine to prevent HPV 16 and/or HPV 18 infections. It was vital, therefore, for GSK to develop the first generation of HPV vaccine to address these two most significant types. Currently research is being conducted within GSK to determine the benefit of adding additional high-risk types in the next generation of vaccine. The question potential cross-protection (beyond 16 and HPV 18 induced recognition and protection against other types through vaccination with HPV 16/HPV 18) is still being investigated, using data from HPV 001 (pivotal evidence of efficacy), HPV 007, HPV 008 and HPV 009. * Refer back to the the ‘Virus’ (section 4) and the ‘Epidemiology’ (section 5) sections of this slide set to review the various oncogenic (high-risk) types if necessary. Refer to question 3 in the ‘Questions on the vaccines’ section of the FAQs. Core reference: Munoz N et al. Int J Cancer 2004; 111: 278–85.

Cross-protekce HPV vakcín Bivalentní vakcína „Naivní“ populace 6 měsiců trvající infekce HPV 45 – 83% HPV 31/45 – 60% HPV 31/33/45/52/58 – 41% Harper DM, Therapy (2008) 5(3), 313-324

Number of cases Placebo Účinnost v prevenci CIN 2/3 a AIS díky cross-protekci u HPV-negativní populace (N=17 599) Kvadrivalentní vakcína CIN 2/3 or AIS* (N=17 599) Number of cases Number of cases Placebo Efficacy 95% CI HPV 31/45 8 21 62% 10, 85 HPV 31/33/45/52/58 27 48 43% 7, 66 31/33/35/39/45/51/52/56/58/59 38 62 38% 6, 60 Composite endpoints were analyzed (primary endpoints). In analyses for the individual components of the endpoints, efficacy was variable, and there was no evidence of efficacy with respect to HPV 35 and 45-related disease. Data presentována na ICAAC kongresu, Chicago Sept 07.

Výskyt persistentní infekce a CIN, VIN a VaIN vyvolaných HPV typy 6/11/16/18 PPE Population 1/Luna/p. 1/col 2/Results/Table: Primary Efficacy Results (Cont). TM 91% Reduction (P < 0.001) Počty případů 92% Reduction (P < 0.001) 89% Reduction (P < 0.001) Key Point Quadrivalent HPV vaccine (GARDASIL) provided a similarly high level of efficacy among women 24 to 34 years of age and those 35 to 45 years of age. Background This slide shows the efficacy of GARDASIL on the combined incidence of persistent infection or cervical/vulvar/vaginal disease related to HPV types 6/11/16/18 for all subjects 24 to 45 years of age in the per-protocol efficacy population and separately for women 24 to 34 years of age and 35 to 45 years of age. Compared with placebo, GARDASIL prevented 91% (95% CI: 74% to 98%) of the combined incidence of persistent infection or cervical/vulvar/vaginal disease caused by HPV Types 6, 11, 16 and 18 in women 24 to 45 years of age. Similar efficacy rates were seen in women 24 to 34 years of age (92%; 95% CI: 67% to 99%) and in women 35 to 45 years of age (89%; 95% CI: 52% to 99%). Reference Luna J, Saah A, Hood S, Bautista O, Barr E, for the FUTURE III Investigators. Safety, efficacy, and immunogenicity of quadrivalent HPV vaccine (GARDASIL™) in women aged 24-45. Poster presented at the 24th International Papillomavirus Congress; November 3-9, 2007; Beijing, China. Presentation No. PA1-04. N = 792 N = 792 N = 823 1/Luna/p. 1/col 2/Results/Table: Primary Efficacy Results (Cont). N = 815 1/Luna/p. 1/col 2/Results/Table: Primary Efficacy Results (Cont).

Cohort of Colombian Women Ženy jsou během svého života vystaveny riziku HPV infekce a souvisejících onemocnění Cohort of Colombian Women N = 1610 Years 10 20 30 40 50 1 2 3 4 5 Age at Baseline 15–19 20–24 25–29 30–44 45+ 1/Muñoz/p. 2081/Figure 2. Cumulative Risk of HPV Infection (%) Key Point The highest risk of HPV infection occurs in adolescents 15–19 years of age, but the risk of infection remains throughout life. Background In this study, a cohort of 1610 HPV-negative Colombian women 15–85 years of age with normal cytologic results at baseline was monitored every 6 months for an average of 4.1 years. Information on risk factors and cervical samples for cytologic testing and HPV DNA detection and typing were collected at each visit.1 This slide shows the lifetime risk of acquiring an infection with any HPV type grouped according to age. For any HPV infection, the highest 5-year cumulative risk (42.5%) was observed among women 15–19 years of age; incidence thereafter decreased monotonically with age, but the lowest level (in women 45 years of age and older) was still 12.4%.1 Reference Muñoz N, Méndez F, Posso H, et al. Incidence, duration, and determinants of cervical human papillomavirus infection in a cohort of Colombian women with normal cytological results. J Infect Dis. 2004;190:2077–2087. 1/Muñoz/p. 2077/ abstract/col 2/¶2/p. 2078/col 1/¶1,2. Adapted from Muñoz N, et al. J Infect Dis. 2004;190:2077–2087. Reprinted with permission from The University of Chicago Press. Copyright © 2004 by the Infectious Diseases Society of America. All rights reserved. 1/Muñoz/p. 2081/Figure 2; p. 2082/col 2/¶5.

perzistentní infekce - kvadrivalentní vakcína První důkaz účinnosti HPV vakcíny u žen starších 26 let Profylaktické podání kvadrivalentní vakcíny bylo vysoce efektivní v prevenci persistentní infekce vyvolané HPV typy 6/11/16/18 cervikálních, vulvárních a vaginálních onemocnění vyvolaných HPV typy 6/11/16/18 abnormálních výsledků onkologické cytologie vyvolaných HPV typy 16/18 Kvadrivalentní vakcína vyvolala ochranné imunitní odpovědi u žen do 45 let věku Key Point GARDASIL is the only HPV vaccine that has been shown to significantly reduce the incidence of persistent infection and clinical disease in women above age 26. Prezentováno na kongresu IPV, China, Peking, Nov 07

Co přinesly 2 roky HPV očkování? Účinnost u vakcinovaných typů je vysoká a dlouhodobá Vysoká imunitní odpověď u obou typů vakcín - i když odlišného typu Pozitivní dopad na lehké preca děložního hrdla Evidence based cross-protektivita účinnost vakcinace je zásadně ovlivněna HPV statutem ženy ideální je podat „naivním“ dívkám…

Co přinesly 2 roky HPV očkování? SOUČASNOST A BUDOUCNOST oportunní podání ženám 26-45 let off label – evidence based - kvadrivalentní vakcína Podání chlapcům 9-15 let(SPC) – již možno Podání mužům High risk populace – gay komunita - anální ca, kondylomata, penilní ca HIV pozitivní, imunodeficitní pacienti nové režimy skríningu - vakcinované x nevakcinované Ideální model z hlediska plošné, primární prevence - plošně ročník 11 až 13-letých - 50 000 dívek skríning musí být i při plošném podávání - cca 20-25% mimo vakcínu - kompletní změny skríningových strategií - perspektivní pozitivní dopad vakcíny - dekády - nutná politická vůle

Co přinesly 2 roky HPV očkování? Děkuji za pozornost marek.pluta@lfmotol.cuni.cz