What factors have most influence on the estimated

In document Human papillomavirus and HPV vaccines: technical information for policy-makers and health professionals (Page 32-42)

benefits from HPV vaccination?

• The magnitude of benefit from HPV vaccination in a country will depend on:

− the burden of HPV disease attributable to the genotypes against which the vaccines protect or, if confirmed, cross-protect;

− vaccine efficacy;

− achievable vaccine coverage;

− duration of protection.

• These factors may differ in different age groups and in populations with high HIV prevalence.

• Both direct protection of those vaccinated and indirect protection of others as a result of reduced HPV transmission in the community need to be considered when different vaccination strategies are evaluated.89, 92, 94

• The introduction of HPV vaccines may affect – positively or negatively – the effectiveness of screening programmes, which may have important consequences.94

• Poorly understood features of HPV epidemiology and natural history (e.g. age- and sex-specific transmission rates, duration of natural immunity, whether reactivation occurs, HPV genotype interaction, natural history of CIN2 and CIN3) hinder modelling work; better data are urgently required.

In general, the most important determinant of overall programme effectiveness will be the cov- erage of pre-adolescent girls with three doses of HPV vaccine. Direct protection of individuals would be expected to decline as age at vaccination increases, since HPV vaccines are prophylactic and

older women will be more likely to have had prior exposure to HPV. However, catch-up campaigns (sometimes used at the start of routine vaccination with a new vaccine) can hasten the decline in inci- dence and result in indirect protection of the popu- lation. Mathematical models can help to determine the costs and benefits of catch-up campaigns; these are likely to depend on the age-specific rates of HPV infection in different countries.

The potential gains from vaccinating males also need to be considered from a population perspec- tive, including indirect (reduced HPV transmission) and direct effects (e.g. prevention of genital warts, penile cancer, anal cancer, RRP, and certain head and neck cancers). The direct cancer prevention effect in boys will be less than in girls, as the inci- dence of HPV-related cancer is lower in men than in women. Results of dynamic simulation models of HPV transmission suggest that, if high coverage of females can be achieved, little additional reduc- tion in cervical cancer is gained by vaccinating males.94, 95 At lower coverage, vaccination of boys may contribute to controlling infection. However, because vaccination directly protects women, more gains may be derived per girl vaccinated than per boy vaccinated. Whether any additional benefits are worth the costs of vaccinating males can be evaluated further in different settings using math- ematical models. Validation of predictions based on these complex models will require long-term implementation studies. Furthermore, consider- ations of the acceptability and likely coverage of a strategy targeting girls only, against one including both sexes, will also be relevant in determining the usefulness of vaccinating boys.

The most important risk period for acquisition of HPV appears to be late adolescence and early adulthood. To obtain maximum benefit from vac- cines, protection must cover this period. The clini- cal trials have shown that efficacy is sustained for at least 4–5 years, and it seems likely that protection may last longer. Thus, declining vaccine efficacy is unlikely to be a major determinant of the benefits of a pre-adolescent programme, though data to confirm this are clearly required.

In countries with organized screening, it will be important to evaluate the effect of HPV vaccination on the screening programme. If those who have been vaccinated no longer attend for screening, because they (wrongly) believe that they are fully protected against cervical cancer, the number of deaths could even increase, especially if vac- cine protection wanes over time.94 It is important, therefore, to use the opportunity presented by the introduction of HPV vaccine to increase awareness of the need for screening.

15. What factors have most

influence on the estimated

costs of HPV vaccination?

• The cost of HPV vaccines is likely to be the major determinant of the cost of a vaccination programme.

• Delivery costs for HPV vaccines are likely to be much higher than for existing vaccines given to infants, since in most developing countries a new programme will be needed.

• Data on costs and coverage of different vac- cination strategies will be obtained from dem- onstration projects planned in four developing countries over the next 1–2 years.

The licensed vaccine is not yet widely available, but where it has been licensed, its current price is over US$100 per dose (i.e. over US$300 for the full course). Manufacturers have declared that they are willing to set different prices for countries with different economic conditions. The price of the vaccine is almost certainly going to be a major determinant of the cost and affordability of any vaccine programme.

Administration costs are likely to vary by country and region. Very few countries have universal programmes for delivering health care to pre- adolescents, so the costs of establishing and maintaining a new system for HPV vaccination are likely to be considerable.96 Demonstration projects

planned by the Program for Appropriate Technology in Health (PATH) in India, Peru, Uganda, and Viet Nam, will help to gather data on the costs of HPV vaccination programmes. If a two-dose schedule could be used, or if vaccines could be given at an earlier age, together with other vaccines (e.g. at school entry or even in infancy), the costs could be reduced. Evaluation of these options is therefore urgently needed.

In developing countries, cervical cancer is the leading cause of cancer death in women; it is estimated that 91% of all HPV-related cancer deaths in the world are due to cervical cancer. HPV vaccines are very effective in preventing infection and disease resulting from vaccine- related HPV genotypes in women who are negative for both HPV DNA and serum antibodies at the time of first vaccination. Protection lasts for at least 5 years and probably much longer. Data are not yet available on the safety and efficacy of HPV vaccines in Africa, or in populations with high HIV prevalence. HPV vaccines will reduce, but not eliminate, the risk of cervical cancer. Screening programmes will still be needed to prevent cervical cancer, even after HPV vaccines are introduced, although the procedures used for screening may need to be adapted.97 The primary target group for HPV vaccines is likely to be pre- adolescent girls (e.g. aged 9–12 years), but the cost-effectiveness of vaccinating other groups needs to be evaluated. Further data on regional and country variations in HPV epidemiology, the


natural history and transmission of HPV infection, the mechanism and duration of protection by HPV vaccines, and the costs and effectiveness of different strategies for vaccination and screening will improve predictions of the benefits to come from these new vaccines.98, 99 More information on the cost-effectiveness of different strategies will become available to guide policy-makers once the price of the vaccine itself is known for countries at different income levels, and when associated delivery costs have been assessed. If a two-dose schedule could be used, or if HPV vaccines could be given at an earlier age with other vaccines (e.g. at school entry or even in infancy), vaccine delivery could be greatly facilitated. Innovative methods will be needed to finance the introduction of HPV vaccines.100 The introduction of HPV vaccines will create opportunities to strengthen health systems. Such opportunities should be taken through the rapid establishment of new partnerships for vaccine delivery, financing and monitoring of impact.7

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