OBJECTIVES: To review incidence rate and burden of illness associated with Human Papillomavirus (HPV) related female genital (cervical, vulvar and vaginal) cancers in Spain. METHODS: Databases and registries searched for data retrieval included EMBASE, PUBMED, Cochrane, Globocan, WHO, SEER and relevant grey literature. Studies reporting epidemiology and costs associated with HPV-related genital cancers in females were of interest. RESULTS: In 2008, age standardized incidence rate of cervical cancer per 100,000 females was 6.3 in Spain compared to 5.7, 7.2, 10.6 and 15.3 in US, UK, Europe and worldwide, respectively (Globocan 2008). The incidence of cervical cancer was highest among Spanish women aged 45-54 years. Incidence rate of vulvar and vaginal cancers ranged from 1.6-4.0 and 0.3-0.7 per 100,000 females, respectively. Additionally, vulvar and vaginal cancers were most common among older women (≥70 and ≥65 years, respectively). In the same year (2008), mortality rate due to cervical cancer was 1.9 per 100,000 females (WHO 2010). Mortality rate for vulvar-vaginal cancer was 9.34% from 1997-2008 (Gil-prieto 2011). Annually, 7.6 million pap smear tests were performed in Spain at the cost of €622 million (Castellsague 2009). Average number of hospitalizations per year was 4151 due to cervical cancer and 17,883 due to vulvar-vaginal cancers. Mean (SD) length of hospital stay due to cervical cancer was 8.7 (15.2) days and 8 (10) days due to vulvar-vaginal cancer (Gil 2007, Gil-prieto 2011). Estimated annual cost of hospitalization due to cervical cancer and carcinoma in situ was €19 million (Gil 2007). Indirect costs (productivity loss) associated with mortality related to cervical cancer were €1.1 million (Oliva 2006).  CONCLUSIONS: HPV-related genital cancers have significant incidence and mortality rate in Spanish women with higher risk in elderly female population. The direct and indirect costs incurred due to genital cancers are substantial and reflect considerable economic burden.