The HPV immunisation programme was introduced in 2008 at which time the vaccine used was Cervarix

Transcription

1 The HPV immunisation programme was introduced in 2008 at which time the vaccine used was Cervarix In September 2012 the vaccine used changed to Gardasil Following a review of the immunological evidence the Joint Committee on Vaccination and Immunisation (JVCI) concluded that the immunogenicity of a twodose schedule was likely to be the same as the three-dose schedule. This resource is designed to facilitate immunisers already participating in the HPV immunisation programme to update their knowledge in respect of the two-dose schedule. It is not designed for healthcare workers who have no previous experience of the HPV immunisation programme. Such staff should consult with their line manager regarding how best to meet their knowledge needs. 0

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7 There are 13 high risk types of HPV that have been associated with cancer. HPV 16 and 18 together cause over 75% of cervical cancers, along with HPV type 31 they account for the majority of cases. Low risk types, particularly 6 and 11, are thought to cause over 90% of cases of genital warts. Other HPV types are the cause of warts on other parts of the body. 6

8 Median time for clearance is eight months. 7

9 For further information see: Syrjanen K, Syrjanen S. Epidemiology of human papilloma virus infections and genital neoplasia. Scand J Infect Dis Suppl. 1990;69:7-17. The 79% is an estimated lifetime risk based on their long term study of a cohort of Finish women and from the abstract In unselected Finish female population at the age of 22 years, the prevalence of clinical (i.e. detectable by PAP smear) HPV infections was about 3%, and the adjusted annual incidence was 8.0%. According to the estimates for the life-time risk, up to 79% of the Finnish females would contract at least one HPV infection within ages 20 to 79 years This is variously reproduced as the statement at least 75% of wmen2, or at least 80% sexually active women by the age of 50. Jit M, Vyse A, Borrow R, Pebody R, Soldan K, Miller E. Prevalence of human papillomavirus antibodies in young female subjects in England. Br J Cancer. 2007:97: Based on our sample, less than 5% of girls under the age of 14 years were seropositive for any HPV type. From age 14 years onwards, the seroprevalence increased sharply until the early 20s, and then stabilised or declined The Scottish data are from the National HPV surveillance programme. A poster publication shows the baseline figures: 8

10 hpv-scotland.pdf 49% had any HPV type, 23. Two had HPV types 16 and/or 18, and 20. Eight had another High Risk Type other than 16/18. Most of these infections will be transient, HPV 16 is associated with persistent infection. 8

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13 The precise proportion of cervical cancers attributed to each HVP type varies by world region and by individual studies. HPV 16 is consistently responsible for the majority of cases and HPV 18 the second most common. A 2007 meta-analysis by Smith and others provided combined figures from studies in Europe: Ref: Smith JS et al, 2007; Int J Cancer 121(3): Link: There is emerging evidence that the vaccines provide a degree of cross protection against other High Risk HPV types that are closely related to the vaccine types. Cervarix - Wheeler et al. Lancet Oncology, January 2012 Gardasil - Brown et al. J Infec Dis

14 The precise proportion of cervical cancers attributed to each HVP type varies by world region and by individual studies. HPV 16 is consistently responsible for the majority of cases and HPV 18 the second most common. A 2007 meta-analysis by Smith and others provided combined figures from studies in Europe: Ref: Smith JS et al, 2007; Int J Cancer 121(3): Link: There is emerging evidence that the vaccines provide a degree of cross protection against other High Risk HPV types that are closely related to the vaccine types. Cervarix - Wheeler et al. Lancet Oncology, January 2012 Gardasil - Brown et al. J Infec Dis

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16 Every year in the UK, over 3000 women will be diagnosed with cervical cancer. Cervical cancer is the most common cancer in women ages 35 and under. Breast cancer is the most common type of cancer diagnosed in women in Scotland and the second in terms of female cancer deaths. New cases of and deaths from breast cancer are 10-fold those of cervical cancer. Cervical screening is credited with saving the lives of 1 in 65 women in the UK born since Peto 2004, The Lancet In Scotland the incidence decreased by 47% between the baseline year of 1986 and Scottish statistics are available at the following links: Cervical cancer: Statistics/Female-Genital-Organ/ Cervical screening: Topics/Cancer/Publications/ / Cervical-Screeningreport.pdf?

17 This figure demonstrates very clearly that the highest number of cases are in young women, as is the highest occurrence. The incidence rises in older women because the population is smaller. 15

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19 This slide illustrates the not inconsiderable burden of genital warts on sexual health services. In Australia where the national HPV immunisation programme was implemented using Gardasil there appears to have been a substantial effect in reducing the clinical burden of genital warts. See: Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data. Basil Donovan, Neil Franklin, Rebecca Guy, Andrew E Grulich, David G Regan, Hammond Ali, Handon Wand, Christopher K Fairley. Lancet Infect Dis 2011; 11: Published Online November 9, 2010 DOI: /S (10)

20 Over 90% of genital warts are caused by the low risk HPV types 6 and 11. The majority of genital HPV infections are asymptomatic; the diagnosis of genital warts is based on clinical examination when warts are visible. Over 7000 new cases are diagnosed in GUM clinics in Scotland each year; numbers of new diagnoses have increased over the past ten years Genital warts can recur, causing significant distress and requiring repeated clinical visits for treatment; in 2007, an additional 4191 episodes f care were provided for people attending GUM clinics for treatment with recurrent infection. Overall there are more new diagnoses in men than women but there are age differences in the distribution of new cases notably a younger age of acquisition in women; two thirds of new diagnoses in women are in those aged compared to 50% in young men. In recent years, the largest increase in diagnoses was observed in those aged Almost 50% of women infected with HPV 6 or 11 will develop genital warts within 12 months, and 64% within 36 months. Winer et al (2005) development and duration of human papillomavirus lesions, after initial infection. J Infect Dis. 191:

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22 As Scotland is one of the only countries to screen women for their first cervical cancer smear at age 20, it is now possible to ascertain the impact of the vaccine on HPV infections in the cervix. This figure shows how those women vaccinated with the three doses of the HPV vaccine have reduced Geno prevalence of infection with HPV 16 and 18. The vaccine is also associated with a reduction in the prevalence of HPV 31, 33 and 45, which suggests that Cerarix offers cross-protection against these other high-risk HPV types. There has been a small increase in HPV 51 in vaccinated women compared with unvaccinated women. * Reference: Kavanagh K, Pollock KGJ et al. Introduction and sustained high coverage of the HPV bivalent vaccine leads to a reduction in the prevalence of HPV 16/18 and closely related HPV types. Brit J Cancer 2014:110(11):

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24 From Cervarix manufactured by GlaxoSmithKlein was the vaccine used in the national HPV immunisation programme. Cervarix is Bivalent vaccine (HPV types 16 and 18). From September 2012 the vaccine used is Gardasil 22

25 The Summary of Product Characteristics (SPC) is available at 0.5ml suspension is a pre-filled syringe (glass) with plunger stopper (siliconized FluroTec-coated bromobutyl elastomer or non-coated chlorobutyl elastomer) and tip cap (bromobutyl). Using the pre-filled syringe Shake well before use. Attach the needle by twisting in a clockwise direction until the needle fits securely on the syringe. Administer the entire dose as per standard protocol. 23

26 Gardasil is not a live vaccine it cannot cause infection. Gardasil does not contain thiomersal Gardasil is latex free Gardasil does not contain porcine gelatin 24

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28 Gardasil must be stored and transported between +2 o C and +8 o C. There is no other stability data for Gardasil routinely. Across the UK, if vaccine wastage is even only 1%, it will cost 2million. Reinforce message to take good care of it! Validated cool boxes and related items such as cool packs should be used when transporting and storing vaccine for use in situations such as school immunisations sessions. Cool boxes should be used in accordance with manufacturer s guidelines to ensure that vaccines are stored at the correct temperature. A realistic calculation of how much vaccine is needed for a particular immunisation session should be made prior to transporting vaccine to a session. During the session, care should be taken to remove only the required amount of vaccine from the cool box in order that unused stock may be returned to pharmacy. 26

29 In 2014, the JCVI considered data concerning a potential move to a two-dose schedule in adolescent girls. JVCI noted that the immunological evidence supported a move to a two-dose schedule. JVCI noted the duration of protection in adolescents vaccinated using a two-dose schedule with the second dose given at least six months after the first was likely to be the same as a three-dose schedule ( 4856/Minutes_HPV_Subcommittee_meeting_Jan_20014_final.pdf) The modelling and cost effectiveness analysis comparing a two-dose schedule to a three-dose schedule indicated a third dose would no longer be cost-effective provided that the duration of protection of a two-dose schedule lasted for twenty years. The minimum time between the first and second dose should be six months with 24 months as the upper limit. The two-dose schedule should be used in adolescent females who commence the HPV vaccination course before they reach 15 years of age, i.e. the first dose must be given before the 15 th birthday. Adolescent females who start a course of HPV vaccination from the age of 15 years should be offered a three-dose schedule. 27

30 There are no data with two-dose schedules for immunocompromised individuals. Therefore a three-dose schedule should be offered to individuals who are HIV positive or are known to be immunocompromised at the time of vaccination. This recommendation is endorsed by WHO SAGE ( Revaccination should be considered after treatment is finished and/or recovery has occurred. Specialists advice may be required. 27

31 The three-dose schedule should be used in adolescent females who commence the HPV vaccination course from 15 years of age, i.e. where the first dose is given after the 15th birthday. There are no data with two-dose schedules for immunocompromised individuals. Therefore a three-dose schedule should be offered to individuals who are HIV positive or are known to be immunocompromised at the time of vaccination. This recommendation is endorsed by WHO SAGE (see Green Book). Revaccination should be considered after treatment is finished and/or recovery has occurred. Specialist advice may be required. For planning purposes, a schedule of 0, 1, 4 to 6 months is appropriate. With regard to any variations, please always consult the latest version of the Green Book chapter online at If there is any discrepancy between the SPC and the Green Book, remember the advice on page 38 of the latter: Healthcare professionals are reminded that in some circumstances the recommendations regarding vaccines given in the Green Book chapters may differ from those in the Summary of product Characteristics (SPC) for a particular vaccine. 28

32 When this occurs, the recommendations in the Green Book are based on current expert advice received from the JCVI and should be followed. 28

33 Please refer to Chapter 18a v2.0 of Green Book for further detail. This advice applies to both Cervarix and Gardasil 29

34 If more than one vaccine is given in same limb, they should be given at least 2.5cm apart. The site at which each vaccine was given should be noted in the individual s records. 30

35 There are very few individuals who cannot receive HPV vaccine. Where there is any doubt advice should be sought from Immunisation Co-ordinator on the circumstances under which vaccine could be given. Gardasil is latex free. (This is contrast to Cervarix in which the rubber plunger and tip cap may contain some latex and therefore Cervarix should not be given to individuals with a history of severe (anaphylactic) allergy to latex). Yeast allergy is not a contraindication to Gardasil Even through Gardasil is grown in yeast cells, the final vaccine product does not contain any yeast. There is no known risk associated with giving inactivated/recombinant viral or bacterial vaccines or toxoids in pregnancy or whilst breast feeding. Since inactivated vaccines cannot replicate they cannot cause infections in either mother or foetus. However, on a precautionary basis HPV vaccine is not advised in pregnancy. If a women finds out she is pregnant after she has started a course of HPV vaccine, she should complete her pregnancy before finishing the three-dose schedule. Termination of pregnancy following inadvertent immunisation is not recommended. In order to follow up any cases where HPV vaccine is inadvertently given in pregnancy all such cases should be reported to Health protection Scotland on

36 Individuals with immunosuppression or with HIV infection (regardless of CD4 counts) should be considered for HPV vaccines in accordance with the recommendations in the national programme. However, individuals who are immunosuppressed may not develop a full antibody response. Specialist advice may be required on reimmunisation when treatment is finished and/or recovery has occurred. 32

37 For a full list of adverse reactions associated with Gardasil refer to the Marketing Authorisation holders Summary of Product Characteristics. Anaphylaxis is a very rare, recognised slide effect of most vaccines and facilities for its recognition and management must be available. 33

38 As with all vaccines and other medicines, healthcare professionals and patients/parents/carers are encouraged to report suspected adverse reactions to the Medicines and Healthcare products Regulatory Agency (MHRA) using the yellow card reporting scheme. 34

39 Presented at EUROGIN 2011, Lisbon Susanne K. Kjaer for the HPV Vaccine Nordic Follow-Up Team 1 Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark 3 Gynaecologic Clinic, Rigshospitalet, University of Copenhagen, Denmark Background The Gardasil long term follow up (LTFU) study is an ongoing extension of a pivotal randomized, placebo-controlled, double-blind, 4 year study to investigate the safety, immunogenicity, and effectiveness of quadrivalent Human Papillomavirus (qhpv) on the incidence of HPV 16/18-related cervical intraepithelial neoplasia (CIN) 2 or worse in 16 to 23 year old women (Protocol 015). Methods Follow-up of subjects will be accomplished in two ways: 1) registry-based follow up for effectiveness data as well as safety data including but not limited to deaths, cancer, and hospitalisation; 2) active follow-up for blood collection for immunogenicity assessments at years five and 10 of the LTFU study. Effectiveness and safety analyses will occur approximately two years following completion of Protocol 015 and approximately every two years thereafter for 10 years. The current report represents the first of these efficacy and safety analyses. Cohort 1 included approximately 2,700 subjects who receive qhpv vaccine at the 35

40 start of Protocol 015. Cohorts 2 consists of approximately subjects who received placebo at the start of Protocol 015 and qhpv vaccine prior to entry into the LTFU. Vaccine effectiveness against HPV 16/18-related CIN 2 or worse was estimated by calculating the expected incidence of CIN 2/3 or worse in an unvaccinated (placebo) cohort using historical data. The primary analysis approach was per-protocol. Results There were 1,080 subjects that contributed to the follow up period out of total of 2,195 eligible subjects in the per-protocol population in Cohort 1. In these subjects there were no cases of HPV vulvar cancer, and vaginal cancer observed. However, the follow up time in persons-years is still insufficient to make a definitive statement about the effectiveness of the HPV vaccine for the current time period. Conclusions The HPV vaccine shows a trend of continued protection in women who were vaccinated up to seven years previously, although there is as yet insufficient data to confirm that protection is maintained. The HPV vaccine continues to be generally safe and well tolerated up to seven years following vaccination. 35

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42 CHSP-S will be populated with data supplied from LA Education departments CHSP-Schools system is updated in Oct/Nov and the class lists are generated from the previous year. It will also be populated with information requested from GPs re girls who may already have received HPV vaccine. 37

43 Leaflets To order more copies of the materials, please contact For alternative formats, including an easy-read version, please These leaflets were distributed to school health teams in June Online Video The online video detailed in the slides replaces the DVD Together we can fight cervical cancer which was produced by NHS Health Scotland for the last campaign. This DVD is no longer current and should be withdrawn from use. 38

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