Cost-effectiveness of the prophylactic HPV vaccine: an application to the Netherlands taking non-cervical cancers and cross-protection into account.

Despite an effective screening programme, 600-700 women are still diagnosed with cervical cancer in the Netherlands each year. In 2009 a prophylactic vaccine against HPV-type 16 and 18 was implemented in the national immunisation programme to decrease the incidence of cervical cancer. There is evidence that infections with several oncogenic HPV types other than the vaccine types 16 and 18 are also prevented by vaccination, also known as cross-protection. Besides cervical cancer, HPV can also cause cancers at other sites such as the oropharynx, vulva, vagina and the anus/anal area. In this study we estimated the maximum health and economic benefits of vaccinating 12-year old girls against infection with HPV, taking cross-protection and non-cervical cancers into account. In the base-case, we found an incremental cost ratio (ICER) of €5815 per quality adjusted life year (QALY). Robustness of this result was examined in sensitivity analysis. The ICER proved to be most sensitive to vaccine price, discounting rates, costs of cervical cancer and to variation in the disutility of cervical cancer.

Cost-effectiveness of prophylactic vaccination against human papillomavirus 16/18 for the prevention of cervical cancer: adaptation of an existing cohort model to the situation in the Netherlands.

Cervical cancer is one of the most prevalent cancers among women worldwide. Implementation of an HPV-vaccination strategy targeting the major oncogenic types 16 and 18 that cause cervical cancer is generally expected to significantly reduce the burden of cervical cancer disease. Here we estimate the costs, savings and health gains with the addition of HPV-16/18 vaccination to the already existing Dutch screening programme. In the base-case analysis, it was estimated that implementation of an HPV-16/18 vaccine would result in an incremental cost-effectiveness ratio (ICER) of euro22,700 per life-year gained (LYG). In sensitivity analysis, the robustness of our finding of favourable cost-effectiveness was established. The ICER appeared sensitive to the vaccine price, discount rate and duration of vaccine-induced protection. From our results, it validly follows that immunization of 12-year-old Dutch girls against HPV-16/18 infection is a cost-effective strategy for protecting against cervical cancer.

Towards an oral influenza vaccine: comparison between intragastric and intracolonic delivery of influenza subunit vaccine in a murine model.

In this paper we investigated to which part of the gastro-intestinal (GI) tract, the upper or lower part, an oral influenza vaccine should be targeted to result in an effective immune response in mice. Our study demonstrates that without adjuvant substantial systemic but low respiratory mucosal immune responses were induced in mice after delivery of influenza subunit vaccine to the upper GI-tract (intragastric) as well as the lower GI-tract (intracolonically). When the vaccine was adjuvanted with Escherichia coli heat-labile enterotoxin (LT) these responses were significantly enhanced. Interestingly, intracolonic administration of vaccine with adjuvant also resulted in enhanced cellular immune responses and the desired Th1-skewing of these responses. Intragastric administration of the adjuvanted vaccine also increased T-helper responses. However, Th1-skewing was absent. In conclusion, the right combination of strong mucosal adjuvant (e.g. LT) and antigen delivery site (e.g. the lower part of the gastro-intestinal tract) might result in effective vaccination via the oral route.