Background: Since the introduction of HPV vaccines, several studies have been conducted in different countries to assess HPV knowledge and vaccine acceptance. The aim of this study was to perform a systematic literature review to summarize results and identify factors associated with HPV knowledge and vaccine acceptance in adolescents and their parents and to compile the measurement tools used in the published research studies performed in European countries where HPV is licensed. Methods: A systematic literature review was conducted for studies published between January 1st 2006 and December 31st 2017. Results: Seventy non-interventional studies performed in 16 European countries met the inclusion criteria. Thirty-eight of them reported data on HPV knowledge and 40 reported data on HPV vaccine acceptance. Further, 51.8% of adolescents (range 0% to 98.6%) and 64.4% of parents (range 1.7% to 99.3%) knew about HPV infection. Insufficient information and safety concerns were the main barriers to vaccination acceptance. Conclusion: HPV knowledge and vaccine acceptance are still modest and vary widely between studies across EU countries. Coordinated efforts should be made to provide the relevant population with information for informed decision-making about HPV vaccination.

Human papillomavirus (HPV) is one of the main causes of infection-related cancer. The bivalent vaccine (2vHPV) (16/18) and quadrivalent (6/11/16/18) HPV vaccine (4vHPV) have been included in the Spanish vaccination calendar since 2007. The new nonavalent HPV vaccine (9vHPV), approved in Europe in 2015, includes nine HPV types 6/11/16/18/31/33/45/52/58 and has been available in Spain since May 2017. Our study aims to estimate the epidemiological impact and the cost-effectiveness of a girls-only and a gender-neutral vaccination program with 9vHPV compared to the current vaccination program in Spain. A dynamic transmission model simulating the natural history of HPV infections was calibrated to the Spanish setting and applied to estimate costs and quality-adjusted life years (QALYs) associated with vaccination strategies using a payer perspective and a 100-year time horizon. A girls-only vaccination strategy at age 12 years with 9vHPV was found to be a cost-effective strategy compared with 4vHPV (incremental cost-effectiveness ratio (ICER) of €7,718 per QALY). Compared with girls-only vaccination with 4vHPV, gender-neutral vaccination with 9vHPV was associated with further reductions of up to 28.5% in the incidence of cervical intraepithelial neoplasia (CIN) 2/3 and 17.1% in the incidence of cervical cancer, as well as with a 14.0% reduction in cervical cancer mortality. Furthermore, a gender-neutral vaccination program with 9vHPV could potentially be cost-effective considering some parameters as head and neck protection or discount rates, leading to a reduction in the burden of HPVrelated diseases in both sexes in the Spanish population.

BackgroundA new nonavalent human papillomavirus (HPV) vaccine that includes genotypes 6/11/16/18/31/33/45/52/58 has been recently approved in Spain. A previous study has shown that attributable fraction of HPV related diseases in Spain is consistent with that reported in European and global studies. The aim of the present study was to estimate the annual direct costs associated to the following HPV-related diseases: genital warts, high grade precancerous lesions and cancer of cervix, vulva, vagina, anus and penis and head and neck cancer, caused by genotypes included in the nonavalent (9vHPV) and quadrivalent vaccines (4vHPV), in Spanish men and women.MethodsCancer registries and epidemiological studies were used to estimate the number of new annual cases of genital warts, anogenital precancerous lesions and cancer of cervix, vulva, vagina, anus, penis and head and neck, as well as the fraction attributable to HPV infection and to genotypes targeted by both vaccines in Spain. Costs per patient for each disease were obtained from the literature. In addition, 142 specialists were surveyed to estimate cost per patient of vulvar, vaginal, anal and penile precancerous lesions. The annual burden of diseases attributable to types targeted by both vaccines was estimated and compared. All results were validated by a panel of experts.ResultsIn 2016, new genital warts, precancerous lesions and cancers attributable to types targeted by the 9vHPV were estimated at 49,251, 29,405 and 3381, respectively. Among them, 12,597 new precancerous lesions and 530 new cancers were related to the 5 additional types covered by the 9vHPV. Annual cost of new cases of these diseases associated to types targeted by the 4vHPV and 9vHPV were estimated at 116.7 and 150.9 million € for the Spanish National Health Service (NHS), respectively (2017 €).ConclusionsHPV-related diseases represent a major burden for the Spanish NHS. Annual new cases and costs related to the 5 additional types from the 9vHPV represent a significant burden compared with that associated to types included in the 4vHPV.Electronic supplementary materialThe online version of this article (10.1186/s13027-018-0187-4) contains supplementary material, which is available to authorized users.

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Background: Cervix uteri cancer is the 4th most common cancer among women worldwide and the second most frequent cancer in women under 45 years old in Spain. We aimed to describe the burden of hospital admissions by malignant neoplasia (MN) and in situ carcinoma (ISC) of the cervix in Spain from 2003 to 2014, a 12-year period that included the first years after introduction of an HPV vaccination program.Methods: This epidemiological study reviewed data from the Ministry of Health National Surveillance System, which includes more than 98% of Spanish hospitals. Hospitalization rate, mortality rate, and case fatality rates were calculated per year and age group.Results: We found 74,933 hospitalizations due to MN and ISC of the cervix. The average age at hospitalization increased significantly during the study period. The average length of hospital stay decreased significantly (p<0.001), while hospitalization costs increased. The mean hospitalization rate was 27.532 cases per 100,000 women (95% CI: 27.335-27.729). This rate decreased significantly during the study period. The mean mortality rate was 1.418 deaths per 100,000 women (95% CI: 1.373-1.463) and the mean case-fatality rate was 5.150% (95% CI: 4.992-5.308).Conclusion: Our study showed a substantial decrease in the hospitalization burden due to cervical disease. This decrease could be attributable to different causes including cervical cancer prevention measures, and changes in disease management. Further research is needed to confirm the cause. This information could contribute to further evaluations of the impact and cost effectiveness analysis of HPV vaccination in Spain.

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