Human papillomavirus (HPV) is the most common sexually transmitted infection and is a well-established cause of anogenital cancers (responsible for over 70% of cervical cancers). Vaccines that target the HPV strains responsible for such cancers elicit virus-neutralising antibody responses, thus preventing the initial infection and some re-infections associated with the same HPV types. Research also suggests that HPV is a risk factor in cancers originating in the upper aero-digestive tract, known as head and neck (H+N) cancers.  OBJECTIVES: To estimate the prevalence, incidence and associated costs of HPV-related anogenital and H+N cancers in England. METHODS: The Hospital Episode Statistics (HES) database was used to estimate the prevalence and incidence of anogenital and head and neck cancers in England from 2002 to 2011. An in-house epidemiologic study and published sources were used to estimate the proportions of these cancers attributable to HPV . Cost estimates using Healthcare Resource Groups (HRGs) in combination with the most recent UK National Tariff will be applied to the data. Estimates for costs outside the scope of the National Tariff (such as rehabilitation costs which, for example, are a key component of H+N cancer treatment pathways) will be derived from expert opinion using resource use surveys. Results will be validated by clinical experts in each cancer included in the analysis. RESULTS: The analyses will highlight key areas of the broader burden of HPV-related cancers and quantify the associated healthcare costs falling on the NHS in England. A proportion of HPV-related cancers can be prevented through vaccination, as such, the analysis aims to capture overall costs and, in turn, the potential for cost offsets through the implementation of preventative healthcare pathways.  CONCLUSIONS: The use of HPV vaccines has the potential to reduce the incidence of a proportion of HPV-related cancers, improving patient quality of life in a cost-effective manner.