Immunization of Early Adolescent Females with Human Papillomavirus Type 16 and 18 L1 Virus-Like Particle Vaccine Containing AS04 Adjuvant

PurposeIn female individuals 15–25-years of age, the AS04-containing human papillomavirus (HPV)–16/18 vaccine is highly immunogenic and provides up to 100% protection against HPV-16/18 persistent infection and associated cervical lesions up to 4.5 years. Optimal cervical cancer prevention will require prophylactic vaccination against oncogenic HPV 16 and 18 before the onset of sexual activity in early adolescent girls. To establish the feasibility of vaccination in girls 10–14 years of age, we compared the immunogenicity and safety in early adolescent female individuals to those 15–25 years in whom vaccine efficacy has been demonstrated.MethodsWe enrolled 773 female participants aged 10–14 years and 15–25 years to receive the HPV-16/18 L1 VLP AS04 vaccine, which was administered at months 0, 1, and 6. Serum samples were collected at months 0 and 7; antibodies to HPV 16 and 18 VLPs were measured by enzyme-linked immunosorbent assay. Vaccine safety was assessed at 7 or 30 days after each dose; serious adverse events were recorded during the entire study period.ResultsBoth age groups achieved 100% seroconversion for HPV 16 and 18. Participants in the group aged 10–14 years were not only noninferior to those 15–25 years in terms of HPV 16 and 18 seroconversion rates but also had approximately twice as high geometric mean titers. The vaccine was generally safe and well tolerated.ConclusionsThese findings suggest that HPV vaccination during early adolescence is generally safe, well tolerated, and highly immunogenic. The observed higher antibody titers in the group 10–14 years of age are likely to result in longer antibody persistence. Overall, these data support the implementation of prophylactic HPV vaccination in this age group.     

Clinical Trial Experience With Prophylactic Human Papillomavirus 6/11/16/18 Vaccine in Young Black Women

PurposeHuman papillomavirus (HPV) is the causative agent of cervical cancer. Black women are disproportionally diagnosed and have higher mortality from cervical cancer in the United States. Here we describe the prophylactic efficacy and safety of a quadrivalent HPV-6/11/16/18 vaccine in black women.MethodsA total of 700 black women from Latin America, Europe, and North America (aged 16–24 years) received the vaccine or placebo in one of two studies. Analyses focused on the efficacy and safety of the vaccine.ResultsBaseline rates of Chlamydia trachomatis infection and history of past pregnancy were more than twice as high in black women compared with the non-black women who were enrolled in these trials. HPV-6/11/16 or 18 DNA was detected in 18% of black women versus 14.6% in non-black women at day 1. For black women, vaccine efficacy against disease caused by HPV-6/11/16/18 was 100% for cervical intraepithelial neoplasia (0 vs. 15 cases; 95% confidence interval, 64.5%–100%) and 100% for vulvar and vaginal intraepithelial neoplasia and condylomata acuminata (0 vs. 17 cases; 95% confidence interval, 69.3%–100%). There were no serious vaccine-related adverse experiences. A similar proportion of pregnancies resulted in live births (75.8% vaccine; 72.7% placebo) and fetal loss (24.2% vaccine; 27.3% placebo).ConclusionsProphylactic quadrivalent HPV-6/11/16/18 vaccination of young black women demonstrated high efficacy, safety, and tolerability. HPV vaccination has the potential to reduce cervical cancer-related health disparities both in the United States and around the world.     

Evaluation of HPV-16 and HPV-18 specific antibody measurements in saliva collected in oral rinses and merocel® sponges

BackgroundCurrent Human papillomavirus (HPV) L1 VLP vaccines protect against HPV-16 and HPV-18-associated cancers, in females and males. Although correlates of protection have not been identified, HPV-specific antibodies at sites of infection are thought to be the main mechanism of protection afforded by vaccination. Oral sampling has gained increased attention as a potential alternative to serum in monitoring immunity to vaccination and understanding local immunity in oral cancers.MethodsSerum was collected via venipuncture, and saliva was collected via oral rinses and Merocel® sponges from healthy volunteers: 16 unvaccinated females, 6 females (ages 24–41) and 6 mid-adult aged males (ages 27–45) recipients of three doses of the HPV-16/18/6/11 vaccine (Gardasil®). Mid-adult male vaccine trial participants were compared to female participants. Samples were tested for anti-HPV-16 and anti-HPV-18 immunoglobulin G levels by an L1 virus-like particle-based enzyme-linked immunosorbent assay (ELISA).ResultsAll vaccinated participants had detectable serum anti-HPV-16 and anti-HPV-18 antibodies. Optimal standard concentration range and sample serial dilutions for oral rinses were determined. The standard curve was not affected by the type of solution examined. Reproducibility of HPV-16 and HPV-18 antibody titers in mouthwash (overall CV < 10%) or in Merocel® extraction buffer was robust (CV < 13%). Excellent assay linearity (R² > 0.9) was observed for sera spiked controls in both solutions. HPV-16 and HPV-18 specific antibodies were detectable in saliva from vaccine recipients, both in mouthwash and in Merocel® sponges but levels were several logs lower than those in serum.ConclusionsThis study confirms the application of HPV-16 and HPV-18 ELISAs currently used in sero-epidemiological studies of immunogenicity of HPV vaccines for use with oral samples. Oral samples may be a useful resource for the detection of HPV-16 and HPV-18-specific antibodies in saliva following vaccination.     

Estimated impact of human papillomavirus vaccines on infection burden: The effect of structural assumptions

Mathematical models have been used to estimate the impact of human papillomavirus (HPV) vaccines on infection burden and cervical cancer. Models assume different mechanisms of naturally acquired immunity against re-infection, but processes of latency and reactivation of latent infection have not been explored. This study uses an individual-based dynamic model to simulate randomised controlled trials (RCTs) for vaccine efficacy, using different assumptions about naturally acquired immunity and viral latency after clearance of HPV infection. Model estimates of vaccine effectiveness are compared to those from published RCTs. We then estimate the impact of the bivalent vaccine on HPV-16 and -18 infection burden in South Africa under these different assumptions. When assuming no latency, simulated vaccine effectiveness overestimates results from RCTs and the model cannot match the observed difference in vaccine effectiveness between total vaccinated cohorts and more HPV-naïve cohorts. The reduction in HPV-16 and -18 burden by 2045, following roll-out of vaccination in 2014, does not depend on assumptions about natural immunity, but models that assume no latency predict ∼25% greater reduction in HPV-16 and -18 burden than models that include reactivation of latent infection for all men and women. Mathematical models that do not allow for reactivation of latent HPV infections may therefore overestimate the long-term impact of HPV vaccines.     

Age-specific human papillomavirus antibody and deoxyribonucleic acid prevalence: a global review

PurposeGlobal data on human papillomavirus (HPV) serological and deoxyribonucleic acid (DNA) prevalence are essential to optimize HPV prophylactic vaccination strategies.MethodsWe conducted a global review of age-specific HPV antibody and studies with both antibody and DNA prevalence for HPV-16, ?18, ?6, and ?11.ResultsOne hundred seventeen studies were included; participants' ages ranged from several hours to >90 years. HPV-16 seroprevalence was generally higher in Africa, Central and South America, and North America, more prevalent among women than among men, and peaked around ages 25–40 years. HPV-18 seroprevalence was generally lower than HPV-16 with a later age peak. Data were limited for HPV-6 and ?11, both of which peaked at ages similar to HPV-18. Among 9–26-year-old females, HPV-16 seroprevalence ranged from 0%–31% in North America, 21%–30% in Africa, 0%–23% in Asia/Australia, 0%–33% in Europe, and 13%–43% in Central and South America. HPV-16/-18 DNA prevalence peaked 10–15 years before corresponding HPV-16/-18 antibody prevalence.ConclusionsFemales within the HPV vaccine-eligible age-group (9–26 years) had a range of dual HPV-16 DNA and serology negativity from 81%–87%, whereas 90%–98% were HPV-16 DNA negative. Serology and DNA data are lacking worldwide for females younger than age 15 years, the prime target group for vaccination.     

Estimation of the potential overall impact of human papillomavirus vaccination on cervical cancer cases and deaths

Background

Human papillomavirus (HPV) vaccination offers potential for primary prevention of HPV-related pre-cancers and cancers as demonstrated in clinical trials. Mathematical models have estimated the potential real-life impact of vaccination on the burden of cervical cancer (CC). However, these are restricted to evaluations in a limited number of countries.

Methods

Potential decline in CC cases and deaths with the AS04-adjuvanted HPV-16/18 vaccine of young girls naïve to HPV, was estimated at steady-state (vaccine coverage: 0–100%) based on clinical trial and country-specific incidence data. Data on vaccine efficacy were taken from the end of study PATRICIA trial of the AS04-adjuvanted HPV-16/18 vaccine. The numbers of cases and deaths due to HPV-16/18 were estimated and compared with those due to any HPV type to estimate the additional cases prevented. This difference estimates CC cases and deaths avoided due to protection against non-vaccine HPV types. Cost-offsets due to reductions in CC treatment were estimated for five countries (Brazil, Canada, Italy, Malaysia and South African Republic) using country-specific unit cost data. Additionally, cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3)-related burden (cases and treatment costs) prevented by vaccination were estimated for two countries (Italy and Malaysia).

Results

HPV vaccination could prevent a substantial number of CC cases and deaths in countries worldwide, with associated cost-offsets due to reduced CC treatment. Cross-protection increased the estimated potential number of CC cases and deaths prevented by 34 and 18% in Africa and Oceania, respectively. Moreover, vaccination could result in a substantial reduction in the number of CIN2/3 lesions and associated costs.

Conclusion

HPV vaccination could reduce the burden of CC and precancerous lesions in countries worldwide, part of disease burden reduction being related to protection against non HPV-16/18 related types.     

Safety and Immunogenicity of the HPV-16/18 AS04-Adjuvanted Vaccine: A Randomized,Controlled Trial in Adolescent Girls

PurposeImmunization of girls against oncogenic human papillomavirus (HPV) types before sexual debut is important for cervical cancer prevention. This phase III blinded, randomized, controlled trial in adolescent girls assessed safety of the HPV-16/18 AS04-adjuvanted vaccine.MethodsGirls (mean age 12 years) in 12 countries received the HPV-16/18 L1 virus-like particle AS04-adjuvanted vaccine (N = 1,035) or hepatitis A virus vaccine as control (N = 1,032) at 0, 1, and 6 months. The primary objective was to compare the occurrence of serious adverse events (SAEs) between groups. HPV-16 and HPV-18 antibody titers were assessed by enzyme-linked immunosorbent assay post-vaccination.ResultsUp to study month 7, 11 girls in the HPV-16/18 vaccine group reported 14 SAEs and 13 girls in the control group reported 15 SAEs. The difference in SAE incidence between groups was .20% (95% CI, ?.78, 1.20). No SAE in the HPV-16/18 vaccine group was considered related to vaccination or led to withdrawal. The incidence of solicited local and general symptoms up to 7 days post-vaccination was moderately higher with the HPV-16/18 vaccine than with control. The incidence of unsolicited symptoms, new onset of chronic diseases, and medically significant conditions was similar between groups. All girls seroconverted for both antigens after three doses of the HPV-16/18 vaccine; geometric mean titers were 19,882.0 and 8,262.0 EU/mL for anti-HPV-16 and -18 antibodies, respectively, in initially seronegative girls.ConclusionsThe HPV-16/18 AS04-adjuvanted vaccine was generally well tolerated and immunogenic when administered to young adolescent females, the primary target of organized vaccination programs.     

Cost-effectiveness of HPV vaccination in the context of high cervical cancer incidence and low screening coverage

BackgroundEstonia has high cervical cancer incidence and low screening coverage. We modelled the impact of population-based bivalent, quadrivalent or nonavalent HPV vaccination alongside cervical cancer screening.MethodsA Markov cohort model of the natural history of HPV infection was used to assess the cost-effectiveness of vaccinating a cohort of 12-year-old girls with bivalent, quadrivalent or nonavalent vaccine in two doses in a national, school-based vaccination programme. The model followed the natural progression of HPV infection into subsequent genital warts (GW); premalignant lesions (CIN 1–3); cervical, oropharyngeal, vulvar, vaginal and anal cancer. Vaccine coverage was assumed to be 70%. A time horizon of 88 years (up to 100 years of age) was used to capture all lifetime vaccination costs and benefits. Costs and utilities were discounted using an annual discount rate of 5%.ResultsVaccination of 12-year-old girls alongside screening compared to screening alone had an incremental cost-effectiveness ratio (ICER) of €14,007 (bivalent), €14,067 (quadrivalent) and €11,633 (nonavalent) per quality-adjusted life-year (QALY) in the base-case scenario and ranged between €5367–21,711, €5142–21,800 and €4563–18,142, respectively, in sensitivity analysis. The results were most sensitive to changes in discount rate, vaccination regimen, vaccine prices and cervical cancer screening coverage.ConclusionVaccination of 12-year-old girls alongside current cervical cancer screening can be considered a cost-effective intervention in Estonia. Adding HPV vaccination to the national immunisation schedule is expected to prevent a considerable number of HPV infections, genital warts, premalignant lesions, HPV related cancers and deaths. Although in our model ICERs varied slightly depending on the vaccine used, they generally fell within the same range. Cost-effectiveness of HPV vaccination was found to be most dependent on vaccine cost and duration of vaccine immunity, but not on the type of vaccine used.     

Cost-effectiveness of human papillomavirus vaccination for prevention of cervical cancer in Taiwan

Background  

Human papillomavirus (HPV) infection has been shown to be a major risk factor for cervical cancer. Vaccines against HPV-16 and HPV-18 are highly effective in preventing type-specific HPV infections and related cervical lesions. There is, however, limited data available describing the health and economic impacts of HPV vaccination in Taiwan. The objective of this study was to assess the cost-effectiveness of prophylactic HPV vaccination for the prevention of cervical cancer in Taiwan.     

Effectiveness of human papillomavirus vaccine against incident and persistent infections among young girls: Results from a longitudinal Dutch cohort study

IntroductionBecause of the long interval between infection with high-risk human papillomavirus (hrHPV) and development of cervical cancer surrogate markers for cancer incidence are necessary to monitor vaccine effectiveness (VE). The aim of this study was to calculate VE of HPV16/18 vaccination by annually assessing incident and persistent infections among (un)vaccinated girls from the general Dutch population up to 3 years after vaccination.MethodsIn 2009, 1668 girls (54% vaccinated) aged 14–16 years were enrolled in a prospective cohort study. Annually, questionnaire data were obtained, and a vaginal swab was tested for type-specific HPV DNA with SPF₁₀-LiPA. VE was estimated by a Poisson model comparing type-specific infection rates in (un)vaccinated girls.ResultsThe adjusted VE (95% CI) was 73% (49–86%) against incident infections with HPV16/18 and 72% (52–84%) against HPV16/18/31/45. VE against persistent HPV16/18 was 100% and 76% (−17 to 95%) against HPV16/18/31/45. This number was lower (36%) when girls who were positive for HPV16 and 18 at baseline were included in the analysis. The overall VE for hrHPV types combined was small. Although 96% of girls were HPV-naïve at baseline, the cumulative 36-month incidence for any HPV was 20%, indicating high sexual activity.DiscussionVaccination is effective against incident and persistent infections with HPV16/18 and HPV16/18/31/45. Low VE against persistent HPV16/18 infection in girls positive at baseline indicates importance of vaccination before sexual debut.     

Smoking and subsequent human papillomavirus infection: a mediation analysis

PurposeSmoking is an established risk factor for a human papillomavirus (HPV) infection advancing to cervical precancer and cancer, but its role earlier in the natural history is less clear. Smoking is inversely associated with possessing HPV antibodies from a past infection suggesting that smoking may influence acquiring subsequent infections.MethodsIn a cohort of 1976 U.S. women, we evaluate whether reduced antibodies to HPV-16 is a mechanism for smoking's role on acquiring a subsequent HPV-16 infection, through the analytic technique of causal mediation analysis. We posit a causal model and estimate two counterfactually defined effects: a smoking impaired antibody-mediated indirect effect and a nonmediated direct effect representing all other potential mechanisms of smoking.ResultsCompared to never smokers, current smokers had increased odds of HPV-16 infection by the antibody-mediated indirect effect (odds ratio [OR] = 1.29; 95% confidence interval [CI]: 1.11, 1.73); the estimated direct effect was very imprecise (OR = 0.57; 95% CI, 0.26–1.13). We observed a stronger estimated indirect effect among women who smoked at least half a pack of cigarettes daily (OR = 1.61, 95% CI, 1.27–2.15) than among women who smoked less than that threshold (OR = 1.09; 95% CI, 0.94–1.44).ConclusionsThis is the first study to directly test the mechanism underlying smoking as an HPV cofactor. The results support current smoking as a risk factor earlier in the natural history of HPV and are consistent with the hypothesis that smoking increases the risk of a subsequent infection by reducing immunity.     

Targeted human papillomavirus vaccination for young men who have sex with men in Australia yields significant population benefits and is cost-effective

BackgroundWe investigated the effectiveness and cost-effectiveness of a targeted human papillomavirus (HPV) vaccination program for young (15–26) men who have sex with men (MSM).MethodsWe developed a compartmental model to project HPV epidemic trajectories in MSM for three vaccination scenarios: a boys program, a targeted program for young MSM only and the combination of the two over 2017–2036. We assessed the gain in quality-adjusted-life-years (QALY) in 190,000 Australian MSM.ResultsA targeted program for young MSM only that achieved 20% coverage per year, without a boys program, will prevent 49,283 (31,253–71,500) cases of anogenital warts, 191 (88–319) person-years living with anal cancer through 2017–2036 but will only stablise anal cancer incidence. In contrast, a boys program will prevent 82,056 (52,100–117,164) cases of anogenital warts, 447 (204–725) person-years living with anal cancers through 2017–2036 and see major declines in anal cancer. This can reduce 90% low- and high-risk HPV in young MSM by 2024 and 2032, respectively, but will require vaccinating ≥84% of boys. Adding a targeted program for young MSM to an existing boys program would prevent an additional 14,912 (8479–21,803) anogenital wart and 91 (42–152) person-years living with anal cancer. In combination with a boys’ program, a catch-up program for young MSM will cost an additional $AUD 6788 ($4628–11,989) per QALY gained, but delaying its implementation reduced its cost-effectiveness.ConclusionsA boys program that achieved coverage of about 84% will result in a 90% reduction in HPV. A targeted program for young MSM is cost-effective if timely implemented.     

Estimating the long-term effects of HPV vaccination in Germany

In Germany, vaccination against the most oncogenic HPV types 16/18 is recommended by the Standing Committee on Vaccination (STIKO) for 12–17 year old girls since March 2007. We developed a dynamic mathematical model for the natural history and transmission of HPV infections to estimate the impact of vaccination on incidence and mortality of cervical cancer and its pre-stages, and on anogenital warts. We focused on an extensive model calibration to epidemiologic data for all stages of the natural history model as well as on a detailed implementation of cervical cancer screening modalities in Germany. Our model predicts first a substantial reduction of cervical cancer incidence and mortality over the next 30 years, which is mainly attributable to an increase in screening participation in the 1990s and not to HPV vaccination, followed by a further reduction attributable to vaccination. Over the next 100 years, HPV vaccination will prevent approximately 37% of cervical cancer cases even if vaccination coverage is only 50% (as currently observed in Germany). Consideration of cross-protection results in a further reduction of approximately 7% of all cervical cancer cases for the bivalent and about 5% for the quadrivalent vaccine in our model. Vaccination of boys was only reasonable if moderate to high vaccination coverage in girls was not achieved. Strategies should be implemented in Germany to increase HPV vaccination coverage among girls thereby making better use of the demonstrated benefits of the vaccine.     

Antibody responses to prophylactic quadrivalent human papillomavirus vaccine at 48 months among HIV-infected girls and boys ages 9–14 in Kenya,Africa

ObjectivesHIV infected children remain at increased risk of HPV associated malignancies as they initiate sexual activity. Though they mount a vigorous immune response to the quadrivalent human papillomavirus (QHPV-6, -11,-16, and -18; Gardasil®) vaccine, durability of the immune response is uncertain. We assessed antibody responses to HPV 6, -11, -16 and -18 for up to 48 months following administration of quadrivalent human papillomavirus vaccine in HIV-infected girls and boys ages 9–14 years in Kenya.DesignOf 178 girls and boys who had previously received three doses of the quadrivalent HPV vaccine, 176 enrolled into extended follow up for 4 years. HPV antibodies to -6, -11, -16 and -18 were measured at 24, 36 and 48 months after the first vaccine dose using the total immunoglobulin G immunoassay (IgG LIA). We evaluated the magnitude and trend in HPV vaccine response and the effect of plasma HIV-1 RNA on HPV vaccine response from month 24 to month 48 of follow up.ResultsAt re-enrollment, 24 months after initial vaccination, median age of participants was 14 years (range 11–17); 167 (95%) were receiving antiretroviral therapy and 110 (66%) had plasma HIV RNA < 40 copies/mL. The rate of HPV seropositivity at 48 months was 83% for HPV-6; 80% for HPV-11; 90% for HPV-16; and 77% for HPV-18. There was a plateau in mean log10 HPV-specific antibody titer between month 24 and 48. The mean log10 HPV-type specific antibody titer for children with undetectable HIV viral load (<40) at the time of vaccination consistently remained higher for the 48 months of follow up compared to children with detectable viral load.ConclusionChildren with HIV infection may retain long term antibody response following HPV immunization. Further work to define whether HIV-infected children are protected from HPV acquisition with low levels of HPV antibodies is needed.     

Introduction of a National HPV vaccination program into Bhutan

BackgroundCervical cancer is the most common cancer in Bhutanese women. To help prevent the disease, the Ministry of Health (MoH) developed a national human papillomavirus (HPV) vaccine program.MethodsMoH considerations included disease incidence, the limited reach of cervical screening, poor outcomes associated with late diagnosis of the disease, and Bhutan's ability to conduct the program. For national introduction, it was decided to implement routine immunization for 12 year-old girls with the quadrivalent HPV6/11/16/18 (QHPV) vaccine and a one-time catch-up campaign for 13–18 year-old girls in the first year of the program (2010). Health workers would administer the vaccine in schools, with out-of-school girls to receive the vaccine at health facilities. From 2011, HPV vaccination would enter into the routine immunization schedule using health-center delivery.ResultsDuring the initial campaign in 2010, over 130,000 doses of QHPV were administered and QHPV 3-dose vaccination coverage was estimated to be around 99% among 12 year-olds and 89% among 13–18 year-olds. QHPV vaccine was well tolerated and no severe adverse events were reported. In the three following years, QHPV vaccine was administered routinely to 12 year-olds primarily through health centers instead of schools, during which time the population-level 3-dose coverage decreased to 67–69%, an estimate which was confirmed by individual-level survey data in 2012 (73%). In 2014, when HPV delivery was switched back to schools, 3-dose coverage rose again above 90%.DiscussionThe rapid implementation and high coverage of the national HPV vaccine program in Bhutan were largely attributable to the strength of political commitment, primary healthcare and support from the education system. School-based delivery appeared clearly superior to health centers in achieving high-coverage among 12 year-olds.ConclusionsBhutan's lessons for other low/middle-income countries include the superiority of school-based vaccination and the feasibility of a broad catch-up campaign in the first year.     

HPV-specific antibodies at the oral cavity up to 30 months after the start of vaccination with the quadrivalent HPV vaccine among mid-adult aged men

BackgroundHPV-16 and HPV-18 cause most oropharyngeal cancers, which are increasing in incidence among males. Although HPV vaccines are highly effective against a number of HPV-associated cancers, efficacy for oropharyngeal cancers has not yet been demonstrated. In addition, the level of antibodies required for protection against oral HPV infection is unknown.Methods150 men ages 27–45 years from Tampa, FL, USA, and Cuernavaca, Mexico, received Gardasil at Day 1, Months 2, and 6. Then, sera and oral gargles were collected one month, 12 months, and 24 months after completion of the three doses (Month 7, 18 and 30 of the study) and tested for anti-HPV-16 and HPV-18 IgG antibody levels by a L1 VLP ELISA.ResultsAll participants developed detectable serum anti-HPV-16 and anti-HPV-18 antibodies and most had detectable antibodies in oral gargles at Month 7 (HPV-16: 93.2%; HPV-18: 72.1%). By months 18 and 30, oral antibodies were detectable in a lower number of participants (HPV-16, 39.8% and 29.6%; HPV-18, 10.7% and 4.6% of individuals, respectively). Overall, oral HPV-16- and 18-specific antibody levels, normalized to total IgG at months 7, 18, and 30, correlated with serum levels (HPV-16, R² = 0.93; HPV-18, R² = 0.91).ConclusionsReduced detectability of oral and serum HPV-16 and HPV-18 antibodies was observed at months 18 and 30 after initiation of the quadrivalent vaccination. However, when detectable, serum and oral HPV-16 and HPV-18 antibody levels were strongly correlated.     

Evaluating human papillomavirus vaccination programs

Human papillomavirus (HPV) has been implicated as the primary etiologic agent of cervical cancer. Potential vaccines against high-risk HPV types are in clinical trials. We evaluated vaccination programs with a vaccine against HPV-16 and HPV-18. We developed disease transmission models that estimated HPV prevalence and infection rates for the population overall, by age group, by level of sexual activity within each age group, and by sex. Data were based on clinical trials and published and unpublished sources. An HPV-16/18 vaccine for 12-year-old girls would reduce cohort cervical cancer cases by 61.8%, with a cost-effectiveness ratio of 14,583 dollars per quality-adjusted life year (QALY). Including male participants in a vaccine rollout would further reduce cervical cancer cases by 2.2% at an incremental cost-effectiveness ratio of 442,039 dollars/QALY compared to female-only vaccination. Vaccination against HPV-16 and HPV-18 can be cost-effective, although including male participants in a vaccination program is generally not cost-effective, compared to female-only vaccination.     

Potential for HPV vaccination and primary HPV screening to reduce cervical cancer disparities: Example from New Zealand

BackgroundCervical cancer rates are over twice as high, and screening coverage is lower, in Māori women compared to other women in New Zealand, whereas uptake of HPV vaccine is higher in Maori females. We aimed to assess the impact of HPV vaccination and the proposed transition to 5-yearly primary HPV screening in Māori and other women in New Zealand, at current participation levels; and additionally to investigate which improvements to participation in Māori females (in vaccination, screening, or surveillance for screening-defined higher-risk women) would have the greatest impact on cervical cancer incidence/mortality.MethodsAn established model of HPV vaccination and cervical screening in New Zealand was adapted to fit observed ethnicity-specific data. Ethnicity-specific models were used to estimate the long-term impact of vaccination and screening (vaccination coverage 63% vs 47%; five-year screening coverage 68% vs 81% in Maori vs European/Other women, respectively).ResultsShifting from cytology to HPV-based screening is predicted to reduce cervical cancer incidence by 17% (14%) in Maori (European/Other) women, respectively. The corresponding reductions due to vaccination and HPV-based screening combined were 58% (44%), but at current participation levels long-term incidence would remain almost twice as high in Māori women (6.1/100,000 compared to 3.1/100,00 in European/Other women). Among strategies we examined, the greatest impact came from high vaccine coverage and achieving higher attendance by Māori women under surveillance for screen-detected abnormalities.ConclusionRelative reductions in cervical cancer due to vaccination and HPV-based screening are predicted to be greater in Maori than in European/Other women. While these interventions have the potential to substantially reduce between-group differences, cervical cancer incidence would remain higher in Maori women. These findings highlight the importance of multiple approaches and the potential influence of factors beyond HPV prevention.     

Immunogenicity and Safety of Human Papillomavirus (HPV)-16/18 AS04-Adjuvanted Vaccine in Healthy Boys Aged 10–18 Years

PurposeThe human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix?) has been shown to be well-tolerated and immunogenic in females aged 10 to 55 years, and up to 100% effective for the prevention of HPV-16/18 infection and associated precancerous cervical lesions in females aged 15 to 25 years. This study is the first to evaluate the immunogenicity and safety of the vaccine in males.MethodsHealthy males aged 10 to 18 years were randomized (2:1 ratio) to receive HPV-16/18 AS04-adjuvanted vaccine (n = 181) or hepatitis B virus (HBV) control vaccine (n = 89) at 0, 1, and 6 months, and were followed for 7 months.ResultsAll initially seronegative subjects in the HPV-16/18 group seroconverted for HPV-16 and 18 (ELISA) at month 2. At month 7, all subjects were seropositive, and the HPV-16 and -18 antibody levels were, respectively, four- and twofold higher than at month 2. The anti-HPV-16 and -18 antibody responses for males aged 10 to 18 years and 10 to 14 years, respectively, were higher than those reported for females aged 15 to 25 years and 10 to 14 years, respectively, in a previous study. The reactogenicity profiles of the HPV-16/18 AS04 and HBV vaccines were similar, except that pain and swelling at the injection site were more common in the HPV-16/18 group. However, vaccine-related symptoms did not affect compliance with the three-dose course, which was equally high (97%) in both groups.ConclusionsThe HPV-16/18 AS04-adjuvanted vaccine is immunogenic and well tolerated in boys aged 10 to 18 years. However, further data on the potential public health benefits of vaccination of boys are required before any recommendations can be made.