Strategies for the introduction of human papillomavirus vaccination: modelling the optimum age- and sex-specific pattern of vaccination in Finland

Abstract

Phase III trials have demonstrated the efficacy of human papillomavirus (HPV) vaccines in preventing transient and persistent high-risk (hr) HPV infection and precancerous lesions. A mathematical model of HPV type 16 infection and progression to cervical cancer, parameterised to represent the infection in Finland, was used to explore the optimal age at vaccination and pattern of vaccine introduction. In the long term, the annual proportion of cervical cancer cases prevented is much higher when early adolescents are targeted. Vaccinating against hr HPV generates greater long-term benefits if vaccine is delivered before the age at first sexual intercourse. However, vaccinating 12 year olds delays the predicted decrease in cervical cancer, compared to vaccinating older adolescents or young adults. Vaccinating males as well as females has more impact on the proportion of cases prevented when vaccinating at younger ages. Implementing catch-up vaccination at the start of a vaccination programme would increase the speed with which a decrease in HPV and cervical cancer incidence is observed. Human papillomavirus (HPV) is a common sexually transmitted agent (Trottier and Franco, 2006) and persistent infection with high risk (hr) types of HPV, most notably types 16 and 18, is the most important risk factor for cervical cancer (Ho et al, 1998). Rates of invasive cervical cancer (ICC) in fertile aged women in Finland declined significantly from 1960 to 1990 (Figure 1), mostly as a result of the national screening programme. However, cervical cancer incidence in Finnish women aged 30 -39 years is now four times higher than 15 years ago (2.9/100 000 in 1986 -1990; 9.8/ 100 000 in 2000: Finnish Cancer Registry, 2006. This is probably due to an increase in incidence and prevalence of hr HPV types in young (23 -28 year old) Finnish women (Laukkanen et al, 2003;Lehtinen et al, 2006).In phase III trials, two HPV virus-like particle vaccines have been shown effective in preventing incident and persistent HPV16 and 18 infection and associated precancerous lesions, with reported efficacies in the region of 90 -100% (Koutsky et al, 2002;Harper et al, 2004Harper et al, , 2006Villa et al, 2005;Mao et al, 2006). The vaccines could prevent around 70% of all cervical cancer (Munoz et al, 2003). One vaccine has recently been licensed for use in the US and in Europe. However, there remain important questions about how a HPV vaccine should be used at a population level (Lowndes and Gill, 2005). These include: the age chosen for vaccination, whether the vaccine is given to female subjects only or to female and male subjects and whether a catch-up vaccination campaign should accompany the introduction of routine vaccination. As mathematical models provide a framework for exploring these questions (Garnett, 2002), we have examined these questions with a model of single-type HPV using the observed epidemiology of HPV in Finland (Barnabas et al, 2006). MATERIALS AND METHODSIn earlier work, we used sexual behaviour data along with HPV seroprevalenc...

Estimating the number needed to vaccinate to prevent diseases and death related to human papillomavirus infection

“…Previous modelling studies have predicted that, if coverage rates are high, vaccination will produce positive herd-immunity effects. 18,19,27 Hence, if high coverage rates are attained (which would be expected in Canada with routine immunization), the population-based number needed to vaccinate will likely be lower than the estimates in our study. On the other hand, if coverage rates are low or if our esti- Canadian data specific to human papillomavirus (HPV) type for infection, cervical intraepithelial neoplasia, cervical cancer and genital warts.…”

“…These assumptions are based on results from clinical trials that showed that prophylactic HPV vaccines were highly effective for at least 5 years, that there is no evidence of waning efficacy and that the vaccine induces robust immune memory, which is the hallmark of long-term protection. 16,17 Similar to other HPV vaccine modelling studies, [18][19][20][21] we assumed that the duration of vaccine protection in the base case is lifelong. However, given the substantial uncertainty around this parameter, we varied the mean duration of protection between 30 years (assuming vaccine protection wanes at 3% per year) and life (previous antibody decay models, based on trial data for HPV type 16, have predicted that the median duration of detectable vaccineinduced serum anti-HPV-16 levels following vaccination range from 32 years to life…”

The value of including boys in an HPV vaccination programme: a cost-effectiveness analysis in a low-resource setting

“…Extending previous work by others (Hughes et al, 2002;Taira et al, 2004;Elbasha and Galvani, 2005;Barnabas et al, 2006;Dasbach et al, 2006;French et al, 2007), we developed a flexible dynamic model of HPV-16 and -18 sexual transmission between males and females. We linked this model to our stochastic model of cervical carcinogenesis that includes nonvaccine targeted (i.e., non-16, -18) high-and low-risk HPV types to assess the cost-effectiveness of including boys in a pre-adolescent vaccination programme in Brazil.…”

Update on Human Papillomavirus (HPV) Vaccines

“…(72) The second model explores the optimal age at vaccination and pattern of vaccine introduction in Finland. (73) The authors find that, once the full impact of vaccination is reached, the annual proportion of HPV type 16-associated cervical cancer cases prevented is expected to be 67% if vaccination of girls occurs at age 15 years, and/or 68% if it occurs at age 12 years, assuming 70% coverage. If vaccination occurs at age 12 years, vaccinating males as well as females is found to prevent an additional 15% of cases annually, if male coverage is 30%.…”