This systematic review assessed the global impact and effectiveness of quadrivalent human papillomavirus (HPV) vaccination on HPV infection and disease in real-world settings over a decade of use. Substantial reductions in HPV 6/11/16/18 infection, anogenital warts, and cervical lesions have been achieved.

BackgroundThe role of human papillomavirus (HPV) in malignant and non-malignant genital diseases in women is well known and the corresponding epidemiological burden has been widely described. However, less is known about the role of HPV in anal, penile and head and neck cancer, and the burden of malignant and non-malignant HPV-related diseases in men. The objective of this review is to estimate the epidemiological burden of HPV-related cancers and non-malignant diseases in men in Europe.MethodsThe annual number of new HPV-related cancers in men in Europe was estimated using Eurostat population data and applying cancer incidence rates published by the International Agency for Research on Cancer. The number of cancer cases attributable to HPV, and specifically to HPV16/18, was calculated based on the most relevant prevalence estimates. The annual number of new cases of genital warts was calculated from the most robust European studies; and latest HPV6/11 prevalence estimates were then applied. A literature review was also performed to retrieve exhaustive data on HPV infection at all anatomical sites under study, as well as incidence and prevalence of external genital warts, recurrent respiratory papillomatosis and HPV-related cancer trends in men in Europe.ResultsA total of 72, 694 new cancer cases at HPV-related anatomical sites were estimated to occur each year in men in Europe. 17,403 of these cancer cases could be attributable to HPV, with 15,497 of them specifically attributable to HPV16/18. In addition, between 286,682 and 325,722 new cases of genital warts attributable to HPV6/11were estimated to occur annually in men in Europe.ConclusionsThe overall estimated epidemiological burden of HPV-related cancers and non-malignant diseases is high in men in Europe. Approximately 30% of all new cancer cases attributable to HPV16/18 that occur yearly in Europe were estimated to occur in men. As in women, the vast majority of HPV-positive cancer in men is related to HPV16/18, while almost all HPV-related non-malignant diseases are due to HPV6/11. A substantial number of these malignant and non-malignant diseases may potentially be prevented by quadrivalent HPV vaccination.

IntroductionA second generation HPV vaccine has been developed for the prevention of anogenital cancers and precancerous lesions of the cervix, vulva, vagina, anus and of genital warts due to nine HPV types.We estimated the annual burden of these diseases attributable to the nine HPV types compared to HPV types from first generation vaccines in women and men in Europe.Material and methodsIncidence rates from the IARC database, cancer registries, the literature and Eurostat population data were used.The burden attributable to the HPV types targeted by both vaccines was estimated by applying the relative contribution of the respective HPV types from epidemiological studies.ResultsIn 2013, the number of new anogenital HPV-attributable cancers was 44,480 with 39,494 of these cases related to second vs. 33,285 to first generation vaccine types.Among the 284,373 to 541,621 new HPV-attributable anogenital precancerous lesions 235,364–448,423 and 135,025–256,830 were estimated to be related to second and first generation vaccine types, respectively.The annual number of new genital warts was 753,608–935,318, with 90% related to HPV6/11.ConclusionsThese data demonstrate how the large public health impact that was achieved by the first generation HPV vaccines could be further increased by second generation vaccines.

BackgroundData on the psychosocial burden of human papillomavirus (HPV)-related diseases other than cervical cancer are scarce. The objectives of this study were to measure and compare the psychosocial burden and the impact on health-related quality of life (HRQoL) of HPV-related lower genital tract diseases and genital warts (GW) using several generic and disease-specific instruments.MethodsOverall, 842 individuals with normal cervical cytology (n = 241), borderline nuclear abnormalities and/or mild dyskaryosis (n = 23), cervical intraepithelial neoplasia (CIN)1 (n = 84), CIN2/3 (n = 203), vulval intraepithelial neoplasia (VIN)2/3 (n = 43), GW (n = 186) and a history of GW (non-current) (n = 62) were included. The generic European Quality of Life Index Version 5D (EQ-5D) questionnaire was completed by patients with GW and VIN2/3. Sexual functioning was evaluated using the Change in Sexual Functioning Questionnaire (CSFQ). Psychosocial impact was measured in women using the HPV Impact Profile (HIP) questionnaire. HRQoL was assessed using a GW-specific questionnaire, the Cuestionario Especifico en Condilomas Acuminados (CECA) (completed by patients with GW and history of GW). For each instrument, scores were compared between groups using the Student's t-test. In addition, utility loss due to GW and VIN2/3 was evaluated by comparing mean EQ-5D scores weighted by age and sex with the UK general population normal values.ResultsA significant psychosocial impact was found in women diagnosed with HPV-related genital diseases, particularly in those with GW. The health state of younger adults with GW was significantly impaired compared with UK normal values (mean EQ-5D index score 0.86 vs 0.94, p < 0.001 for 18–24-year-olds; 0.87 vs 0.93, p = 0.030 for 25–34-year-olds). VIN2/3 was found to have a significant negative impact on sexual functioning, and women with VIN2/3 had a highly impaired health state compared with women in the UK general population (weighted mean EQ-5D index score 0.72 vs 0.89, p < 0.001; weighted mean Visual Analogue Scale score 62 vs 85, p < 0.001).ConclusionsHPV-related lower genital tract lesions and GW significantly impair psychosocial wellbeing and HRQoL. The psychosocial aspects of HPV-related diseases need to be considered when evaluating the potential benefit of HPV vaccination.

BackgroundIn addition to cervical cancer, human papillomavirus (HPV) is responsible for a significant proportion of cancers and precancerous lesions of the vulva, vagina, anus, penis, head and neck, as well as genital warts. We estimated the annual number of new cases of these diseases attributable to 9-valent HPV vaccine types in women and men in Europe.MethodsThe annual number of new cancers of the cervix, vulva, vagina, anus, penis, and selected head and neck sites in the population of the European Medicines Agency territory was estimated based on age-specific incidence rates extracted from Cancer Incidence in 5 Continents, Volume X and Eurostat population data for 2015. The annual number of new cancers attributable to 9-valent HPV vaccine types was estimated by applying the HPV attributable fraction from reference publications based on a large European multicenter study. For non-cervical cancers, HPV attributable fractions were based on oncogenically-active HPV infections only (i.e., detection of HPV DNA and either mRNA and/or p16 positivity). For precancerous lesions of the cervix, vulva, vagina, and anus, and for genital warts, previously published estimations were updated for the 2015 population.ResultsThe annual number of new cancers attributable to 9-valent HPV vaccine types was estimated at 47,992 (95% bound: 39,785-58,511). Cervical cancer showed the highest burden (31,130 cases), followed by head and neck cancer (6,786 cases), anal cancer (6,137 cases), vulvar cancer (1,466 cases), vaginal cancer (1,360 cases), and penile cancer (1,113 cases). About 81% were estimated to occur in women and 19% in men. The annual number of new precancerous lesions (CIN2+, VIN2/3, VaIN2/3, and AIN2/3) and genital warts attributable to 9-valent HPV vaccine types was estimated at 232,103 to 442,347 and 680,344 to 844,391, respectively.ConclusionsThe burden of cancers associated with 9-valent HPV vaccine types in Europe is substantial in both sexes. Head and neck cancers constitute a heavy burden, particularly in men. Overall, about 90% of HPV-related cancers, 80% of precancerous lesions, and 90% of genital warts are expected to be attributable to 9-valent HPV vaccine types each year, demonstrating the important preventive potential of the 9-valent HPV vaccine in Europe.Electronic supplementary materialThe online version of this article (doi:10.1186/s13027-017-0129-6) contains supplementary material, which is available to authorized users.