Burden Of HPV-related Diseases Research Articles

Perception and knowledge of HPV-related and vaccine-related conditions among a large cohort of university students in Italy

ABSTRACT HPV is involved in cervical, anal, penile, vulvar and oropharyngeal cancers, as well as genital warts. It is important to investigate knowledge and attitudes among university students, considering in this age a shift in healthcare decision-making from parents to students themselves. The aim of this study was to estimate knowledge and perception of HPV in terms of potential shame for HPV-related conditions, trust in vaccine efficacy and worry for potential side effects. The study involved students (18–25 years old) from the Universities of Padua and Verona, Italy. Socio-demographic and behavioural characteristics were collected with a questionnaire (n = 9988). Female gender and older age were positively associated with higher knowledge. The adjusted logistic regression showed an association between the set of perceptions investigated and the vaccination status, while a direct connection with knowledge was not found. However, another adjusted linear regression showed that a good set of perceptions could be partially explained by a high level of knowledge. Perceptions seem to fill an intermediate position between the knowledge and the decision to get vaccinated. The potential shame deriving from asking for HPV-vaccination was not identified as a relevant barrier. Having received information from healthcare workers, family and school showed to be positively associated with the adhesion to the vaccination policy. This study identifies university students as a possible target for HPV vaccination and pinpoints specific areas that might be targeted as first to encourage vaccine uptake. Primary prevention together with screening programmes remains essential in further reducing the burden of HPV-related diseases.

Challenges to optimising uptake and delivery of a HPV vaccination programme for men who have sex with men

ABSTRACT Human papillomavirus (HPV) vaccine programmes targeted at men who have sex with men (MSM) may reduce HPV-related disease burden among this at-risk group in countries where uptake of the vaccine among adolescent girls is sub-optimal and where adolescent boys are not routinely vaccinated. There are challenges to optimising the impact of a MSM programme: ensuring good uptake, understanding the effectiveness of the vaccine in this population and considering the longevity of the programme. Furthermore, monitoring of uptake and ensuring that delivery of the programme does not deprive other aspects of sexual health service resources may present challenges to programme evaluation and delivery. We draw on experience from the UK HPV vaccination programme for MSM, delivered in sexual health and HIV clinics, to better understand these challenges with the aim of supporting the implementation of similar programmes elsewhere in the world.

Safety of a quadrivalent human papillomavirus vaccine in a Phase 3, randomized, double-blind, placebo-controlled clinical trial among Chinese women during 90 months of follow-up

BackgroundA quadrivalent human papillomavirus (qHPV) vaccine (HPV6/11/16/18) has demonstrated efficacy and acceptable safety in international studies. However, these studies did not include participants from mainland China, which has a substantial burden of HPV-related disease. This is the first safety report with a follow-up period of up to 90 months from a randomized, double-blind, placebo-controlled trial of qHPV vaccine in Chinese women 20–45 years of age. MethodsParticipants were randomized 1:1 to receive three doses of qHPV vaccine or placebo (Day1, Month 2, and Month 6). Efficacy outcomes are reported elsewhere. Injection-site and systemic adverse events (AEs) were collected using vaccination report cards (VRCs) for 15 days following each vaccination. Serious AEs (SAEs), pregnancy outcomes, new medical conditions, and fetal/infant SAEs were collected during the entire study. ResultsOf 3006 participants randomized, AEs were reported by 926 (61.8%) qHPV vaccine recipients and 856 (57.1%) placebo recipients over the entire study. Four participants (two in each group) discontinued the study vaccination due to AEs that were considered vaccination-related. Within 15 days following any vaccination, injection-site AEs prompted for on the VRC were more frequent among qHPV vaccine recipients (37.6% vs 27.8%), and systemic AEs prompted for on the VRC were similar in frequency between qHPV vaccine and placebo groups (46.8% vs 45.1%). Thirty-eight and 43 participants reported SAEs in qHPV vaccine and placebo groups, respectively. No SAE was considered qHPV vaccine-related. Pregnancy outcomes, fetal/infant SAEs, and new medical conditions were generally similar in frequency between the qHPV vaccine and placebo groups, and within normal ranges. ConclusionThe qHPV vaccine was well tolerated and demonstrated a favorable safety profile in Chinese women 20–45 years of age, consistent with findings from global trials and safety surveillance studies.Trial registration: clinicaltrials.gov; NCT00834106.

The impact of 10 years of human papillomavirus (HPV) vaccination in Australia: what additional disease burden will a nonavalent vaccine prevent?

Background: A National human papilloma virus (HPV) Vaccination Programme for the prevention of HPV infection and associated disease using the quadrivalent HPV vaccine (4vHPV) has been funded and implemented in Australia since 2007, initially for girls only and extended to boys in 2013, with uptake rates among the highest observed worldwide. Aim: We report on the impact of this national programme on HPV prevalence and associated disease burden and estimate the potential impact of adopting a nonavalent HPV (9vHPV) vaccine. Methods: We performed a non-systematic literature review of studies measuring the burden of HPV-associated disease and infection in Australia before and after introduction of HPV vaccination. We also included key national reports with estimates of HPV-related disease burden. Results: Substantial declines in high-grade cervical disease and genital warts among vaccine-eligible women have been observed. Reductions in genital warts incidence and HPV prevalence among heterosexual men of similar age were observed before introduction of the male vaccination programme, indicating a substantial herd effect. 9vHPV vaccine is expected to prevent up to 90% of cervical and 96% of anal cancers. Of an estimated 1,544 HPV-associated cancers in 2012, 1,242 would have been preventable by the 4vHPV vaccine and an additional 187 anogenital cancers by the 9vHPV vaccine. Conclusions: Vaccination using 4vHPV vaccine has had a large demonstrable impact on HPV-related disease in Australia. A switch to 9vHPV could further reduce the HPV-associated cancer burden. With continued high coverage among both males and females, elimination of vaccine-type HPV disease seems achievable in Australia.

A Brief Provider Training Video Improves Comfort With Recommending the Human Papillomavirus Vaccine.

The American Academy of Pediatrics California Chapter 3 created a 20-minute training video targeting barriers to strong provider recommendation of the human papillomavirus (HPV) vaccine. The video included clinical vignettes featuring pediatricians modeling counseling techniques with vaccine-hesitant families. Ninety-six multidisciplinary providers (including pediatric residents) at 6 sites viewed the video and completed baseline and posttest questionnaires assessing their vaccine knowledge, attitudes toward vaccination, and comfort with skills needed to facilitate vaccination. Following the intervention, providers had substantial and statistically significant ( P < .05) improvements in multiple areas assessed, particularly knowledge of the burden of HPV-related disease in males and changes in vaccine response with age; likelihood of "strongly agreeing" that vaccination should not be delayed beyond preadolescence and that HPV vaccine is safe; and feeling "very comfortable" counseling vaccine-hesitant parents and facilitating vaccine completion. This cost-effective and easily disseminated training modality shows promise in increasing provider comfort with HPV vaccine counseling.

Abstract C89: Examining HPV awareness, sexual behavior, and intent to receive the HPV vaccine among racial/ethnic males 18-27

Abstract Background: HPV plays a significant role in cancers and diseases that impact males directly including penile, oral, and anal malignancies, but awareness and positive vaccine intention in males remain problematic. HPV research largely focuses on cervical cancer prevention, ultimately feminizing HPV and erroneously portraying HPV as an infection that does not affect men. Incidence rates of oropharyngeal and anal cancers associated with HPV are increasing, and these cancers disproportionately affect men. Additionally, racial/ethnic minority men are disproportionately affected by HPV-related diseases and cancers. Black and Hispanic men are diagnosed with more HPV-related cancers and HPV-related cancers at later stages compared to other racial/ethnic groups. To date, very few studies have focused on HPV among racial/ethnic minority men and sexual. The purpose of this study is to examine 1) the awareness of men about HPV and their sexual behaviors and 2) the association of their intent to receive the HPV vaccination and sexual behaviors among racial/ethnic men. Methods: Racial/ethnic minority men age 18 to 27 (n=190) attending a large public university in the southeast US completed a 20-minute web-based survey in the fall of 2011. Survey items were adapted from previous research of psychosocial HPV studies among men and women, and were based on constructs from the Health Belief Model and Social Cognitive Theory. This analysis examined self-reported data on participants' sociodemographics, sexual behavior, HPV knowledge, vaccine status, and intent to receive HPV vaccination. Univariate analyses examined the sample distribution; Bivariate analyses were conducted to examine racial/ethnic differences sexual behavior and intent to receive the HPV vaccination, and binomial logistic regression analysis examined associations between intent to receive HPV vaccination and sexual behaviors. Results: The mean age of the sample was 21.31 (SD=2.579) years. The men identified themselves as Hispanic or Latino/a (49.5%), African-American /Black (17.9%), Asian (13.7%), Other (12.1%), and White (6.8%). The majority of the sample was insured (79.5%), unmarried/single (83.7%), heterosexual (91.1%), and completed 2 years of college or less (45.3%). Frequency distributions indicated that 73.2% did not consider themselves to be virgins and 49.5% of the sample was currently sexually active. In addition, 79.5% of the sample had previous knowledge about HPV, 81.6% of the sample had not received a dose of the HPV vaccine, and 77.1% did not plan to receive the HPV vaccine. Bivariate analyses showed that Hispanic and Black men were less likely to identify as virgins (p=0.03), more likely to have had vaginal (p=0.01) and oral (p=0.045) sex, and more likely to have vaginal sex at an earlier mean age compared to Asian, White, and Other men. Men who reported having had vaginal sex (28.6%; p=0.01), not being virgins (28.1%; p=0.008), and who were currently sexually active (31.8%; p=0.06) were more likely to have intentions of getting the HPV vaccination. Binomial logistic regression analysis showed that men who thought the HPV vaccine was of moderate importance were more likely than men who thought the HPV vaccine was of low and high importance to intend to receive the HPV vaccine (p=0.02). Conclusion: Although this mostly racial/ethnic minority sample of men were knowledgeable about the HPV vaccine and reported being sexually active, they were still less likely to intend to receive the vaccine. Providing information about HPV at early ages, particularly for Black and Hispanic men, and that it is transmitted through the different sexual behaviors may increase and emphasize the importance of HPV vaccination. Determining factors associated with HPV vaccine intentions among those at risk for HPV is important in increasing uptake of the vaccine and decreasing the burden of HPV-related diseases. Citation Format: Dexter L. Cooper, Natalie D. Hernandez, Tiffany Zellner-Lawrence. Examining HPV awareness, sexual behavior, and intent to receive the HPV vaccine among racial/ethnic males 18-27 [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C89.

High risk human papillomavirus prevalence and genotype distribution among women infected with HIV in Manaus, Amazonas

BackgroundHuman immunodeficiency virus (HIV)-positive women have a high prevalence of human papillomavirus (HPV), and are infected with a broader range of HPV types than HIV-negative women. We aimed to determine the prevalence of cervical cytologic abnormalities, high-risk (HR)-HPV prevalence, type distribution according to the severity of cervical lesions and CD4 cell count and identify factors associated with HR-HPV infection among women living with HIV in Manaus, Amazonas.MethodsWe enrolled 325 women living with HIV that attended an infectious diseases referral hospital. Each woman underwent a gynecological exam, cervical cytology, HR-HPV detection by Polymerase chain Reaction (PCR) using the BD Onclarity™ HPV Assay, colposcopy and biopsy, when necessary. We assessed the associations between potential risk factors and HR-HPV infection.ResultsOverall, 299 (92.0%) women had a PCR result. The prevalence of HR-HPV- infection was 31.1%. The most prevalent HR-HPV types were: 56/59/66 (32.2%), 35/39/68 (28.0%), 52 (21.5%), 16 (19.4%), and 45 (12.9%). Among the women with HR-HPV infection (n = 93), 43.0% had multiple infections. Women with HPV infection showed higher prevalence of cervical abnormalities than that HPV-negative (LSIL: 22.6% vs. 1.5%; HSIL: 10.8% vs. 0.0%). The prevalence of HR-HPV among women with cytological abnormalities was 87.5% for LSIL and 100.0% for HSIL. Women with CD4 < 200 cell/mm3 showed the highest HR-HPV prevalence (59.3%) although this trend was not statistically significant (p-value = 0.62). The mean CD4 cell count decreased with increasing severity of cervical lesions (p-value = 0.001). The multivariable analysis showed that increasing age was associated with a decreased risk of HR-HPV infection with an adjusted prevalence odds ratio of 0.9 (95.0% CI: 0.9–1.0, p-value: 0.03) for each additional year. The only factor statistically significant associated with HR-HPV infection was CD4 cell count.ConclusionsHR-HPV and abnormal cytology prevalence are high among women in the Amazonas. The low CD4 cell count was an important determinant of HPV infection and abnormal cytological findings. HPV quadrivalent vaccination used in Brazil might not offer protection for an important fraction of HPV-related disease burden in women living with HIV. This is partly explained by the high presence of non targeted vaccine HR-HPVs, such as the HPV genotype groups 56/59/66, 35/39/68 and individually HPV-52 and HPV-45, some of which contribute to high-grade lesion.

PP130 Economic Burden Of Nine Human Papillomavirus Strains (HPV9)-Related Diseases: A Real World Cost Analysis From Italy

Introduction:The objectives of this study were to estimate the economic burden of human papillomavirus (HPV) in Italy, accounting for total direct medical costs associated with nine major HPV-related diseases, and to provide a measure of the burden attributable to HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 infections.Methods:A cost-of-illness incidence-based model was developed to estimate the incidences and costs of invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, oropharyngeal, anogenital warts, and recurrent respiratory papillomatosis (RRP) in the context of the Italian National Health System (NHS). We used data from hospital discharge records (HDRs) of an Italian region and conducted a systematic literature review to estimate the lifetime cost per case, the number of incident cases, the prevalence of HPV9 types. Costs of therapeutic options not included in the diagnosis-related group (DRG) tariffs were estimated through a scenario analysis.Results:The total annual direct costs were EUR 540.7 million, with a range of EUR 338.3 – EUR 789.7 million. These costs could increase considering innovative therapies for cancers treatment (range EUR 16.2 – EUR 37.6 million). The fraction attributable to the HPV9 genotypes without innovative cancers treatment was EUR 329.2 million (range EUR 150.1 – EUR 576.7 million), accounting for sixty-one percent of the total annual burden of HPV-related diseases in Italy. Of this amount, EUR 136.7 million (forty-two percent) was related to men, accounting for sixty-four percent of the costs associated with non-cervical conditions.Conclusions:The infections by HPV9 strains and the economic burden of non-cervical HPV-related diseases in men were found to be the main drivers of direct costs. The fraction of the total direct lifetime costs attributable to infections by HPV9 strains and the economic burden of non-cervical HPV-related diseases in men were found to be the main drivers of direct costs.

Burden of Disease of Human Papillomavirus (HPV): Hospitalizations in the Marche and Veneto Regions. An observational study.

HPV (human papillomavirus) is the virus most often responsible for sexually transmitted infections. The burden of HPV-related diseases on hospital resources represents a major public health problem. The aim of this study was to assess the economic burden of HPV-related diseases (anal cancer, genital cancer, genital warts, oropharyngeal cancer) on hospital resources in two Italian regions. A retrospective, non-randomized, observational study was developed in the Marche and Veneto Regions, based on patients receiving hospitalization between 2008 and 2011. All hospitalizations were identified through administrative archives, according to the International Classification of Diseases (ICD-9 CM) to which a defined tariff was assigned. We identified 5299 hospitalized patients in Veneto and 1735 in the Marche Region. The mean annual hospitalization rate was 49.44 per 100,000 individuals in Veneto and 48.41 in Marche. The total mean annual cost attributable to HPV-related diseases was €5.78 (SD 0.80) million in Veneto and €2.24 (SD 0.17) million in Marche. Costs associated with genital cancer amounted to €1.61 million in Veneto and €1.06 million in Marche (28% and 47% of the total mean annual cost, respectively). Oropharyngeal cancer accounted for 36% in Veneto (€2.08 million) and 28% in Marche (€632,645). Hospitalization costs related to anal cancer were €882,567 in Veneto and €377,719 in Marche; genital warts accounted for €1.19 million in Veneto and €171,406 in Marche. Finally, the mean cost per patient was €4364 in Veneto and €5176 in Marche. The present work estimated the cost of HPV-related diseases for hospitalized patients in two Italian regions. The considerable estimated annual economic burden is a powerful driver for the governance of the public health sector.

Cost analysis of Human Papillomavirus-related cervical diseases and genital warts in Swaziland.

BackgroundHuman papillomavirus (HPV) has proven to be the cause of several severe clinical conditions on the cervix, vulva, vagina, anus, oropharynx and penis. Several studies have assessed the costs of cervical lesions, cervical cancer (CC), and genital warts. However, few have been done in Africa and none in Swaziland. Cost analysis is critical in providing useful information for economic evaluations to guide policymakers concerned with the allocation of resources in order to reduce the disease burden.Materials and methodsA prevalence-based cost of illness (COI) methodology was used to investigate the economic burden of HPV-related diseases. We used a top-down approach for the cost associated with hospital care and a bottom-up approach to estimate the cost associated with outpatient and primary care. The current study was conducted from a provider perspective since the state bears the majority of the costs of screening and treatment in Swaziland. All identifiable direct medical costs were considered for cervical lesions, cervical cancer and genital warts, which were primary diagnoses during 2015. A mix of bottom up micro-costing ingredients approach and top-down approaches was used to collect data on costs. All costs were computed at the price level of 2015 and converted to dollars ($).ResultsThe total annual estimated direct medical cost associated with screening, managing and treating cervical lesions, CC and genital warts in Swaziland was $16 million. The largest cost in the analysis was estimated for treatment of high-grade cervical lesions and cervical cancer representing 80% of the total cost ($12.6 million). Costs for screening only represented 5% of the total cost ($0.9 million). Treatment of genital warts represented 6% of the total cost ($1million).ConclusionAccording to the cost estimations in this study, the economic burden of HPV-related cervical diseases and genital warts represents a major public health issue in Swaziland. Prevention of HPV infection with a national HPV immunization programme for pre-adolescent girls would prevent the majority of CC related deaths and associated costs.

Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence.

In 2014, the Food and Drug Administration approved a new human papillomavirus 9-valent vaccine (9vHPV), targeting nine HPV types: HPV types 6, 11, 16, and 18, which are also targeted by the quadrivalent HPV vaccine (qHPV), plus five additional high cancer risk HPV types (HPV types 31, 33, 45, 52, and 58). The aim of the current study was to systematically retrieve, qualitatively and quantitatively pool, as well as critically appraise all available evidence on 9vHPV from randomized controlled trials (RCTs). We conducted a systematic review of the literature on 9vHPV efficacy, immunogenicity and safety, as well as a systematic search of registered, completed, and ongoing RCTs. We retrieved and screened 227 records for eligibility. A total of 10 publications reported on RCTs' results on 9vHPV and were included in the review. Sixteen RCTs on 9vHPV have been registered on RCT registries. There is evidence that 9vHPV generated a response to HPV types 6, 11, 16 and 18 that was non-inferior to qHPV. Vaccine efficacy against five additional HPV type-related diseases was directly assessed on females aged 16-26 years (risk reduction against high-grade cervical, vulvar or vaginal disease = 96·7%, 95% CI 80·9%-99·8%). Bridging efficacy was demonstrated for males and females aged 9-15 years and males aged 16-26 years (the lower bound of the 95% CIs of both the geometric mean titer ratio and difference in seroconversion rates meeting the criteria for non-inferiority for all HPV types). Overall, 9vHPV has been proved to be safe and well tolerated. Other RCTs addressed: 9vHPV co-administration with other vaccines, 9vHPV administration in subjects that previously received qHPV and 9vHPV efficacy in regimens containing fewer than three doses. The inclusion of additional HPV types in 9vHPV offers great potential to expand protection against HPV infection. However, the impact of 9vHPV on reducing the global burden of HPV-related disease will greatly depend on vaccine uptake, coverage, availability, and affordability.

The burden of HPV-related diseases in Italy, 2001–12

Human papillomavirus (HPV) infection is the main cause of cervical cancer and plays a relevant role in the development of genital warts and of the cancer of penis and anus, head/neck, oropharynx and genitourinary system. The aim of this study is the evaluation of hospitalizations due to HPV-related pathologies in 2001-12 in Italy. The national hospital discharge forms were provided by the Ministry of Health. The HPV-related hospitalizations were identified using specific diagnostic codes, accordingly to the ICD-9-CM coding system. The proportion of hospitalizations of potentially HPV-related pathologies, obtained from the literature, was evaluated as well as the hospitalization rates (hr) and their trend over time. Uterine cervical cancer and CIN III accounted for 40% of hospitalizations (hr: 15.6/100 000 and 17.6/100 000, respectively). Head/neck and oropharynx pathologies accounted for 24.5% of cases (hr: 16/100 000 and 3.9/100 000, in males and females, respectively), followed by genital warts (17.3% of hospitalizations; hr: 7.5/100 000 in males and 8.52/100 000 in females), anal (8.1% of hospitalizations), genitourinary (7.7%) and penis cancers (2.2%). The study, even if limited to the evaluation of hospitalizations, points out how HPV-related pathologies continue to be a relevant public health issue in Italy with a high impact on population.

Human Papillomavirus Vaccination Uptake in Canada: A Systematic Review and Meta-analysis.

Human papillomavirus (HPV) is the most commonly sexually transmitted infection in the world and the primary cause of cervical cancer. Canada introduced publicly funded HPV vaccination programs in 2006. The objectives of this study are twofold and aim to (1) determine the levels and (2) examine the various factors influencing vaccine uptake among the general Canadian population. A literature search was conducted on seven databases, followed by screening, methodological quality review (using modified Newcastle-Ottawa Scale), and data extraction. Pooled meta-analysis and a subgroup analysis were conducted stratifying by a number of variables (age, sex, type of program, and method of payment) determined apriori. A total of 718 peer-reviewed articles were initially identified with 12 remaining after screening and underwent methodological quality review. HPV vaccination uptake in Canada varied from 12.40% (95% confidence interval [CI] 6.77–20.26) to 88.20% (95% CI 85.72–90.39). The pooled random effects model showed the HPV vaccination uptake to be 55.92% (95% CI 44.87–66.65). The subgroup analysis showed that vaccination uptake was 66.95% (95% CI 55.00–77.89) in participants ≤ 18 years as compared to 13.58% (95% CI 10.93–16.46) in participants > 18 years. Uptake for females was higher 57.23% (95% CI: 45.40–68.66) when compared to that of 47.01% (95% CI: 0.82–97.75) in males. HPV vaccine uptake among school-based programs was 69.62% (95% CI 57.27–80.68) as compared to 18.66% (95% CI 6.66–34.92) for community-based programs. Vaccination uptake for publicly funded programs was significantly higher 66.95% (95% CI 55.00–77.89) when compared to 13.58% (95% CI 10.92–16.46) for programs where participants had to pay out of pocket. To prevent infections and reduce the burden of HPV-related diseases (including cervical cancer), communities should be made aware and encouraged to vaccinate their children. There is a documented need to direct effort and focus interventions toward improving HPV vaccination uptake in Canada.

Impact and cost-effectiveness of selective human papillomavirus vaccination of men who have sex with men

Men who have sex with men (MSM) have a high lifetime risk of anogenital warts and cancers related to infection with human papillomavirus (HPV). They also benefit less from herd protection than heterosexual males in settings with female-only HPV vaccination. We evaluated the potential health impact and cost-effectiveness of offering vaccination to MSM who visit genitourinary medicine (GUM) clinics. We used a mathematical model of HPV 6/11/16/18 sexual transmission within an MSM population in England, parameterized with sexual behaviour, GUM attendance, HPV prevalence, HIV prevalence, warts, and cancer incidence data. Interventions considered were offering HPV vaccination to either HIV-positive MSM or MSM regardless of HIV status, for age bands 16-25, 16-30, 16-35, and 16-40 years. Substantial declines in anogenital warts and male HPV-related cancer incidence are projected to occur following an offer of vaccination to MSM. MSM not attending GUM clinics will partially benefit from herd protection. Offering vaccination to HIV-positive MSM up to age 40 is likely to be cost-effective if vaccine procurement and administration costs are below £96.50 a dose. At £48 a dose, offering vaccination to all MSM up to age 40 is likely to be cost-effective. Quadrivalent HPV vaccination of MSM via GUM clinics is likely to be an effective and cost-effective way of reducing the burden of HPV-related disease in MSM.

WOLVES – impact of HPV vaccination in Wolfsburg, Germany

Objectives: In Germany data on the epidemiology of HPV infections and especially on the impact of HPV vaccination are rare. WOLVES (Wolfsburg HPV epidemiology study) is the first population based surveillance study in Germany to measure the impact of HPV vaccination and the burden of HPV related diseases in a two different birth cohorts.

Retrospective analysis of HPV 16/18-related disease burden using archival clinical samples.

Estimation of HPV-related disease burden lies at the core of effective disease management. HPV testing is heavily reliant on its retrospective detection in archival clinical cancer samples, especially in parts of the world where HPV screening is not routinely practiced. During the last decade, valuable insights were gained through regional reports based on occasional screening of cervical smears or biopsy sections for the presence of high-risk HPV. HPV 16 and 18 were found to be predominant high-risk HPV subtypes with some regional differences and incidences of co-infections, detected mostly through PCR-based methods. In cases of multiple infections, the presence of viral DNA may not signify its etiologic involvement. The current study, therefore, combines PCR-based detection method with the immunohistochemical (IHC) detection of early viral protein E6 expression, in order to obtain a reliable read out for the disease causing viral subtype, especially in cases of co-infections with oncogenic subtypes other than HPV 16 and 18. Immunohistochemistry (IHC) and PCR-based methods are routinely used laboratory techniques in local hospitals. The concordance between IHC and PCR-based analyses may be useful for determining effective method for the retrospective testing of HPV 16 and 18 disease-related burden. A total of 49 paraffin-embedded cervical cancer biopsy sections representing patients from the northwest region of the country were collected from the tertiary care hospital for this study. Genotyping for HPV 16 and 18 was carried out through PCR. The HPV 16/18 E6 protein expression was evaluated by IHC and was compared with the clinicopathological features of cervical cancer. Molecular analysis of 33 (67%), E6-expressing paraffin-embedded cervical cancer biopsy sections revealed the presence of HPV 16 (n=23; 47%), HPV 18 (n=6; 12%) and co-infection (n=4; 8%) in 49 tumors through PCR. Despite the PCR-based detection of viral DNA in 37 cervical cancer samples, IHC analysis of E6 expression revealed the etiological involvement of HPV 16/18 in 33 out of 37 cervical cancer samples. Overall, there was 85% concordance in the results of the two techniques. IHC analysis provides more conclusive evidence regarding the etiological involvement of the viral subtypes, especially in the presence of multiple infections. About two-thirds (67%) of cervical cancer samples were found to be caused due to HPV 16/18. Latent occurrence of HPV 16 and 18 is suggested in less than 10% cervical cancer samples which were found to harbor viral DNA without E6 expression. Furthermore, E6 expression was found to be significantly correlated with the tumor grade.

Assessment of the Broader Economic Consequences of HPV Prevention from a Government-Perspective: A Fiscal Analytic Approach.

BackgroundCervical cancer poses a substantial burden in terms of morbidity, mortality, and economic losses, especially in low/middle-income countries. HPV vaccination and/or cervical cancer screening among females may reduce the burden of HPV-related diseases, including cervical cancer. However, limited funds may impede the implementation of population-based programmes. Governmental investments in the prevention of infectious disease may have broader economic and fiscal benefits, which are not accounted in conventional economic analyses. This study estimates the broader economic and fiscal impacts of implementing HPV vaccination and/or cervical cancer screening in Indonesia from the perspective of the government.MethodsA government-perspective quantitative analytic framework was applied to assess the Net Present Value (NPV) of investment on cervical cancer prevention strategies including HPV vaccination, cervical screening and its combination in Indonesia. All monetary values were presented in International Dollars (I$).ResultsBased on a cohort of 10,000,000 Indonesian 12-year-old females, it was estimated that HPV vaccination and/or cervical cancer screening result in a positive NPV for the Indonesian government. The combination of cervical screening and HPV vaccination generated a substantial reduction of cervical cancer incidence and HPV-related mortality of 87,862 and 19,359, respectively. It was estimated that HPV vaccination in combination with cervical screening is the most favorable option for cervical cancer prevention (NPV I$2.031.786.000), followed by HPV vaccination alone (NPV I$1.860.783.000) and cervical screening alone (NPV I$375.244.000).ConclusionIn addition to clinical benefits, investing in HPV vaccination and cervical screening may yield considerable fiscal benefits for the Indonesian governments due to lifelong benefits resulting from reduction of cervical cancer-related morbidity and mortality.

Epidemiology and Burden of Disease Associated with HPV Infection

Infection with certain types of human papillomavirus is associated with approximately 660,000 cancers and over 350 million cases of genital warts annually. This ubiquitous virus is transmitted by skin-to-skin contact, including through sexual contact. Of the 40 types infecting the anogenital tract, approximately 15 are considered carcinogenic, particularly types 16 and 18 which are the commonest types found in women diagnosed with invasive cervical cancer. HPV has oncogenic potential at the cervix, vagina, vulva, penis, anus, and certain head and neck cancers. Benign disease is expressed as genital warts and the very rare condition of laryngeal papillomatosis. Infection with oncogenic types of HPV is considered essential in nearly all invasive cervical cancers and a varying percentage of the other HPV-related cancers. Recently, two HPV vaccines, the bivalent and quadrivalent vaccines, have become commercially available and both have shown high immunogenicity and efficacy. The vaccine is prophylactic, and current recommendations are to administer the vaccines to girls 9–12 years of old and, in settings with increasing resources, to extend the target group to boys and to older girls up to 26 years. The combination of vaccine and screening has the potential to significantly reduce the burden of HPV-related disease.

Can high overall human papillomavirus vaccination coverage hide sociodemographic inequalities? An ecological analysis in Canada

BackgroundHuman papillomavirus (HPV) vaccination programs have been implemented in more than 50 countries. These programs offer tremendous promise of reducing HPV-related disease burden. However, failure to achieve high coverage among high-risk groups may mitigate program success and increase inequalities. We examined sociodemographic inequalities in HPV vaccination coverage in 4 Canadian provinces (Quebec (QC), Ontario (ON), Manitoba (MB), British Columbia (BC)). MethodsWe obtained annual HPV vaccination coverage of pre-adolescent girls at provincial and regional levels, from the start of programs to 2012/2013. Regions refer to administrative areas responsible for vaccine implementation and monitoring (there are 18/36/10/16 regions in QC/ON/MB/BC). We obtained regions’ sociodemographic characteristics from Statistics Canada Census. We used univariate weighted linear regression to examine the associations between regions’ sociodemographic characteristics and HPV vaccination coverage. ResultsProvincial HPV vaccination coverage is generally high (QC:78%; ON:80%; MB:64%, BC:69%, 2012/13). QC had the highest provincial vaccination coverage since the program start, but had the greatest inequalities. In QC, regional HPV vaccination coverage was lower in regions with higher proportions of socially deprived individuals, immigrants, and/or native English speakers (p<0.0001). These inequalities remained stable over time. Regional-level analysis did not reveal inequalities in ON, MB and BC. ConclusionSchool-based HPV vaccination programs have resulted in high vaccination coverage in four Canadian provinces. Nonetheless, high overall coverage did not necessarily translate into equality in coverage. Future work is needed to understand underlying causes of inequalities and how this could impact existing inequalities in HPV-related diseases and overall program success.

Epidemiology and Burden of Disease Associated with HPV Infection

Human papillomavirus (HPV) infection is a carcinogen for the following human sites: cervix, vulva, vagina, penis, anus and oropharynx. Approximately 4.8 % of the global cancer incidence (in 2008) was attributable to HPV infections, although substantial differences were found by geographical region. The large majority (85 %) of the cancers attributed to HPV are cancers of the cervix, which were the fourth most common cancers worldwide among women in 2012. There is a clear correlation between the incidence (and mortality) of cervical cancer and the average level of development. Approximately 84 % (445,000 cases) of the total number of cervical cancer cases occur in the less developed regions (particularly, sub-Saharan Africa, Asia and South/Central America). Uniform declines in cervical cancer incidence rates have been observed in countries where effective screening programmes have been put in place. However, increasing trends in cervical cancer incidence have been observed, e.g., in Eastern Europe, most likely as a consequence of an increased exposure to HPV infection and limited screening. A similar pattern of rising rates emerges in low-resource regions including sub-Saharan African countries (Uganda, Zimbabwe) where high-quality incidence data series are available. Incidence and mortality rates for HPV-related cancers other than cervix are low, but recent increases in anal and oropharyngeal cancers have been observed in some populations. The combined use of HPV vaccination and HPV-based testing in screening programmes should accelerate the decline of cervical cancer to reduce the burden of HPV-related diseases.