سود بالینی و مقرون به صرفه ی واکسن ویروس پاپیلومای انسانی برای زنان بزرگسال در هلند

Background The use of human papillomavirus (HPV) vaccines has been universally approved for women from age 12 to 25 years, but those older than 16 years receive no reimbursement for the cost of the vaccine in the Netherlands. Reductions in the vaccine price as well as new insights in the efficacy of HPV vaccines offer renewed arguments to consider HPV vaccination in adult women. We calculated the clinical benefit and cost-effectiveness of vaccinating women aged 17–25 years in 2010. Methods The calculations were based on an individual-based simulation model for cervical carcinogenesis, with HPV infection risks obtained from a type-specific HPV transmission model. The indirect protective effect from vaccinating 12 to 16 year-old girls was adjusted for. Cervical screening in the model was incorporated according Dutch screening guidelines, i.e. 7 cytology-based rounds at 5-year intervals from the age of 30. As base-case, we assumed the vaccine to offer full protection against HPV16/18 only if no prior exposure to that type had occurred before vaccination. In sensitivity analyses, we considered partial cross-protection against types 31/33/45/58 and efficacy against all future infections, irrespective of previous or current infection status. Results In base-case analyses, vaccinating 17 year-olds reduced their lifetime risk of treatment for precancerous lesions from 7.77% to 3.48% and their lifetime cervical cancer risk from 0.52% to 0.24%. These risks were 6.12% and 0.45%, respectively, for a 25 year-old vaccinee. The incremental cost-effectiveness ratio (ICER) for vaccinating 17–25 year-olds was €22,526 per quality-adjusted life-year (QALY) at a vaccine price of €65 per dose, a 50% reduction of the 2010 pharmacy price in the Netherlands. If cross-protection against types 31/33/45/58 was included, the ICER decreased to €14,734 per QALY. Results were robust to efficacy assumptions with respect to previous or current infection status. Conclusion The clinical benefit of HPV vaccination of women up to 25 years moderately depends on cross-protection to non-vaccine types. Refunding the cost of the vaccine to 17–25 year-old women in the Netherlands can be considered cost-effective at anticipated price reductions.

Cervical cancer is the second most common cancer among women worldwide [1]. Cytological screening has greatly reduced the burden of cervical disease in countries that have implemented wide-scale screening programmes [2]. In the Netherlands, the age-standardised incidence rate of cervical cancer has dropped from around 15 per 100,000 women in the 1960s to around 5 per 100,000 women since 2000 [3] and [4]. In 2008, 699 women were diagnosed with invasive cervical cancer and 244 women died from cervical cancer according to the Dutch cancer registry [www.ikcnet.nl]. Several analyses have suggested that the age-standardised incidence and mortality rate of cervical cancer will not be reduced further by cytological screening alone [5], [6] and [7]. The availability of human papillomavirus (HPV) vaccines, however, offering protection against the two most prevalent HPV types in cervical cancer, is expected to contribute to a substantial decrease in the cervical cancer incidence in the next thirty years [8] and [9]. The use of HPV vaccines in women has been universally approved from age 12 up to 25 years (EMEA; FDA). So far, Australia has been the only country to publicly fund a vaccination programme for all women in this age group [10]. In other countries, inclusion into national HPV immunization programmes is restricted to (pre-)adolescent girls, mainly because HPV vaccine trials have demonstrated greatest immunogenicity and efficacy in preventing vaccine-type infections among women without evidence of (prior) type-specific infection at the time of vaccination [11] and [12]. As vaccine-type HPV is highly transmissible [13], the clinical benefit of vaccination after initiation of sexual activity is still uncertain. In the Netherlands, vaccinating girls older than 16 years was not considered feasible from an economic viewpoint – given that the two available HPV vaccines (Gardasil® and Cervarix®) were rather expensive following licensure – and from a clinical point of view, since HPV DNA was detected in cervical smears and HPV16/18 antibodies were found in blood from 16 years off; indicating that these women were not always HPV naïve [14]. New insights in HPV transmission, in the efficacy of HPV vaccines, and reductions in the vaccine price offer renewed arguments to consider HPV vaccination in adult women. In this study, we evaluate the clinical benefit and cost-effectiveness of vaccinating women from age 17 to 25 years compared to no vaccination in these age groups. In all analyses, we include vaccination of 12–16 year-old girls and screening from 30 to 60 years of age – i.e. the current HPV vaccination and cervical screening programmes in the Netherlands. The presented estimates are obtained from a simulation model for cervical carcinogenesis that is linked to a dynamic HPV transmission model [9]. An earlier version of this model has been used for assessing the cost-effectiveness of vaccinating 12 year-old girls in the Netherlands [15].

The clinical benefit of HPV vaccination of women up to 25 years moderately depends on cross-protection to non-vaccine types. Refunding the cost of the vaccine to 17–25 year-old women in the Netherlands can be considered cost-effective at anticipated price reductions.