Abstract and Background
Abstract
Background: Recently, provincial health programs in Canada and elsewhere have begun rolling out vaccination against human papillomavirus for girls aged 9–13. While vaccination is voluntary, the cost of vaccination is waived, to encourage parents to have their daughters vaccinated. Adult women who are eligible for the vaccine may still receive it, but at a cost of approximately CAN$400. Given the high efficacy and immunogenicity of the vaccine, the possibility of eradicating targeted types of the virus may be feasible, assuming the vaccination programs are undertaken strategically.
Methods: We develop a mathematical model to describe the epidemiology of vaccination against human papillomavirus, accounting for a widespread childhood vaccination program that may be supplemented by voluntary adult vaccination. A stability analysis is performed to determine the stability of the disease-free equilibrium. The critical vaccine efficacy and immunogenicity thresholds are derived, and the minimum level of adult vaccination required for eradication of targeted types is determined.
Results: We demonstrate that eradication of targeted types is indeed feasible, although the burden of coverage for a childhood-only vaccination program may be high. However, if a small, but non-negligible, proportion of eligible adults can be vaccinated, then the possibility of eradication of targeted types becomes much more favourable. We provide a threshold for eradication in general communities and illustrate the results with numerical simulations. We also investigate the effects of suboptimal efficacy and immunogenicity and show that there is a critical efficacy below which eradication of targeted types is not possible. If eradication is possible, then there is a critical immunogenicity such that even 100% childhood vaccination will not eradicate the targeted types of the virus and must be supplemented with voluntary adult vaccination. However, the level of adult vaccination coverage required is modest and may be achieved simply by removing the cost burden to vaccination.
Conclusion: We recommend that provincial healthcare programs should pay for voluntary adult vaccination for women aged 14–26. However, it should be noted that our model results are preliminary, in that we have made a number of simplifying assumptions, including a lack of age-dependency in sexual partner rates, a lack of sexual activity outside of the vaccine age-range among females and a uniform age of sexual debut; thus, further work is desired to enhance the external generalisability of our results.
Background
Human papillomavirus (HPV) produces epithelial tumors of the skin and mucous membranes. There are over 100 types, many of which are relatively benign. However, some types have emerged as high risk because they produce lesions that may lead to carcinomas. Resulting disease includes genital warts, respiratory papillomatosis, and cancer of the cervix, vulva, vagina, anus and the penis, as well as cancers of the head and neck. Prevalence of HPV in Canada has been estimated at 24% in female university students. In Ontario, 500 women are diagnosed with cervical cancer annually, leading to 140 deaths. Between 30 and 40 types are transmitted through sexual contact. Without condoms, risk of transmission, given contact with an infected partner, is close to 90%; this risk is still high (40%) when condoms are used. No antivirals have been developed for HPV and detection has largely relied on the recommended yearly pap smear, which locates cellular abnormalities that indicate that HPV may be present.
Cervical cancer is the second most common cause of death in women (after breast cancer) and it accounts for 10% of all cancers in women. Progression to malignancy after acquisition of HPV usually takes at least 10 years. Types 16 and 18 account for approximately 70% of these cervical cancers. Merck and GlaxoSmithKline (GSK) have developed commercial vaccines which target types 16 and 18. Merck's vaccine also protects against types 6 and 11, which are responsible for 90% of external genital warts. The combination of a successful vaccine and vaccination strategy, in combination with the yearly pap smear, seems to be the best approach towards preventing cervical cancer. The vaccine has been approved for women aged 9–26. Current studies are showing 90–100% efficacy as well as over 98% immunogenicity rates for existing vaccines, with no loss of immunity for at least 5 years. Current vaccination programs against HPV consider two distinct groups: girls who have not yet begun to be sexually active and women under 26 who are sexually active.
Vaccination programs in Canada have begun in several provinces (Ontario, Nova Scotia, Prince Edward Island) in Fall 2007, targeting school children aged 9–13. The vaccine is covered by Canadian healthcare for girls in this age group, but is voluntary. Sociological research suggests that about 77% of parents would immunize their children with the HPV vaccine. Vaccination of women aged 14–26 is available, but not covered by provincial healthcare, costing approximately CAN$400 for a full course (three doses). State-funded voluntary HPV vaccination for adults has been underway in other countries, such as France and Australia, since early 2007. Possible limitations of a vaccination program include: i) the vaccine may only be delivered to a proportion p of the population, ii) the vaccine may only confer immunogenicity in a proportion ε of the vaccinated population (ie the vaccine may not always take when administered to the patient), iii) the vaccine may have incomplete efficacy ψ (ie the vaccine doesn't always protect against infection during sexual intercourse), iv) the vaccine may wane over time and v) the vaccine does not target all HPV types.
In this paper, we develop a mathematical model to evaluate the effectiveness of supplementing a childhood vaccination program with voluntary adult vaccination. We address the following research questions: 1. Can a childhood-only vaccination program eradicate targeted types of HPV? 2. Should an adult vaccination program supplement childhood vaccination? 3. Is eradication of targeted types possible for vaccines with suboptimal efficacy or immunogenicity?