Megan A. Smith

The predicted impact of HPV vaccination on male infections and male HPV-related cancers in Australia.

Australia implemented a National HPV Vaccination Program in 2007, with routine vaccination of 12-13 year old females and catch-up in females aged 13-26 years to 2009. The aim of this study was to estimate the impact of the current female-only national vaccination program on males, and then to estimate the incremental benefits to males from being included in the program. We used preliminary data to estimate vaccination coverage in females. We then fitted a dynamic model of sexual behaviour and HPV transmission in Australia to local data on female pre-vaccination age-specific HPV prevalence, predicted the corresponding pre-vaccination prevalence in males due to heterosexual transmission, and modelled the short and long term impact of female-only versus female-and-male vaccination programs. The estimated 3-dose female coverage rates were 78% (range 70-80%) for ongoing coverage in 12-13 year old girls; and from 74% (range 70-80%) in 14 year olds, to 25% (range 15-35%) for women aged 26 years old in 2007. The median estimate for age-standardised pre-vaccination HPV 16 prevalence in females and males aged 15-59 years was 3.2% (95% range: 2.4-4.1%) and 3.1% (95% range: 2.2-4.2%), respectively. The current program in females is predicted to result in a 68% reduction in male HPV 16 infections by 2050, leading to an estimated long term reduction of 14% in rates of cancers of the head, neck and anogenital area. The estimated proportion of the maximum possible vaccine-conferred benefit to males from a female-and-male program which will be achieved by female-only vaccination is 73% (range in probabilistic sensitivity analysis: 53-78%). In conclusion, up to three-quarters of the maximum possible vaccination-conferred benefit to males due to reduced heterosexual transmission will be achieved by the existing female-only program.

The predicted impact of vaccination on human papillomavirus infections in Australia

Vaccines based on human papillomavirus (HPV) 16 and 18 virus‐like particles have the potential to prevent ∼70% of cervical cancers. In Australia, public vaccination against HPV commenced in April 2007, and includes routine vaccination of females aged 12–13 years, and a 2‐year school and GP‐based catch‐up in females aged 12–26 years. The objectives of this study were to estimate initial vaccination coverage rates, to describe current patterns of sexual behavior in young females, and to predict the impact of vaccination on HPV16 infections. We reviewed early coverage data, estimating that coverage in 2007/2008 will reach 86% (feasible range 67–90%) for 12‐ to 13‐year‐old girls, with lower rates attained in older females. A review of survey data found that the median age of first intercourse in Australian females is 16 years, with ∼90% of women sexually active at 22 years. Using these data, we performed an analysis of HPV transmission to predict the impact of vaccination on HPV infection rates. The public program is predicted to result in a reduction in the age‐standardized incidence of HPV16 infections of 56% by 2010 (feasible range 48–61%), and 92% by 2050 (feasible range 76–95%). Elective vaccination of older women and vaccination of males may provide some incremental gains, but the benefits to women of vaccinating males will be less if coverage of females remains high. In conclusion, the current vaccination program is expected to result in a substantial and rapid reduction in the incidence of HPV16 in Australia.

Fall in Genital Warts Diagnoses in the General and Indigenous Australian Population Following Implementation of a National Human Papillomavirus Vaccination Program: Analysis of Routinely Collected National Hospital Data

BACKGROUND Human papillomavirus (HPV) vaccination targeting females aged 12-13 years commenced in Australia in 2007, with catch-up vaccination of females aged 13-26 years continuing to 2009. Whole-population analyses, including effects on the Indigenous population, have not previously been reported. METHODS All hospital admissions between 1999-2011 involving a diagnosis of genital warts were obtained from a comprehensive national database. We compared the age-specific rates before to those after implementation of the vaccination program, according to sex and other characteristics. RESULTS Admission rates decreased from mid-2007 in females aged 12-17 years (annual decline, 44.1% [95% confidence interval {CI}, 35.4%-51.6%]) and from mid-2008 in females and males aged 18-26 years (annual declines, 31.8% [95% CI, 28.4%-35.2%] and 14.0% [95% CI, 5.1%-22.1%], respectively). The overall reductions from 2006-2007 to 2010-2011 were 89.9% (95% CI, 84.4%-93.4%) for females aged 12-17 years, 72.7% (95% CI, 67.0%-77.5%) for females aged 18-26 years, and 38.3% (95% CI, 27.7%-47.2%) for males aged 18-26 years. Compared with the average annual number before program implementation, about 1000 fewer hospital admissions involved a warts diagnosis during 2010-2011. Reductions after program implementation were similar for Indigenous (86.7% [95% CI, 76.0-92.7]) and non-Indigenous (76.1% [95% CI, 71.6%-79.9%]) females aged 15-24 years (P(heterogeneity) = .08). CONCLUSIONS National population-based hospital data confirm previous clinic-based reports of a marked decline in genital warts diagnoses among young people in Australia after program implementation, including indirect benefits to males. The impact of HPV vaccination appears to be similar in young Indigenous and non-Indigenous females.

Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic models

Summary Background Modelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination. Methods We searched MEDLINE and Embase for transmission-dynamic modelling studies published between Jan 1, 2009, and April 28, 2015, that predicted the population-level impact of vaccination on HPV 6, 11, 16, and 18 infections in high-income countries. We contacted authors to determine whether they were willing to produce new predictions for standardised scenarios. Strategies investigated were girls-only vaccination and girls and boys vaccination at age 12 years. Base-case vaccine characteristics were 100% efficacy and lifetime protection. We did sensitivity analyses by varying vaccination coverage, vaccine efficacy, and duration of protection. For all scenarios we pooled model predictions of relative reductions in HPV prevalence (RRprev) over time after vaccination and summarised results using the median and 10th and 90th percentiles (80% uncertainty intervals [UI]). Findings 16 of 19 eligible models from ten high-income countries provided predictions. Under base-case assumptions, 40% vaccination coverage and girls-only vaccination, the RRprev of HPV 16 among women and men was 0·53 (80% UI 0·46–0·68) and 0·36 (0·28–0·61), respectively, after 70 years. With 80% girls-only vaccination coverage, the RRprev of HPV 16 among women and men was 0·93 (0·90–1·00) and 0·83 (0·75–1·00), respectively. Vaccinating boys in addition to girls increased the RRprev of HPV 16 among women and men by 0·18 (0·13–0·32) and 0·35 (0·27–0·39) for 40% coverage, and 0·07 (0·00–0·10) and 0·16 (0·01–0·25) for 80% coverage, respectively. The RRprev were greater for HPV 6, 11, and 18 than for HPV 16 for all scenarios investigated. Finally at 80% coverage, most models predicted that girls and boys vaccination would eliminate HPV 6, 11, 16, and 18, with a median RRprev of 1·00 for women and men for all four HPV types. Variability in pooled findings was low, but increased with lower vaccination coverage and shorter vaccine protection (from lifetime to 20 years). Interpretation Although HPV models differ in structure, data used for calibration, and settings, our population-level predictions were generally concordant and suggest that strong herd effects are expected from vaccinating girls only, even with coverage as low as 20%. Elimination of HPV 16, 18, 6, and 11 is possible if 80% coverage in girls and boys is reached and if high vaccine efficacy is maintained over time. Funding Canadian Institutes of Health Research.

Prevention of cervical cancer in rural China: evaluation of HPV vaccination and primary HPV screening strategies.

Comprehensive evaluation of the cost-effectiveness of HPV vaccination in China has not previously been performed. The objective of this study was to evaluate vaccination as an alternative or addition to primary HPV screening with careHPV (Qiagen, Gaithersburg, USA), and to assess the threshold total cost per vaccinated girl (CVG) at which strategies involving vaccination would become viable compared to screening-only strategies in rural China. We used data from field studies in Shanxi Province to support modelling of HPV vaccination and screening, including local information on sexual behaviour, HPV prevalence, test accuracy, treatment protocols and costs. We evaluated several strategies involving screening once or twice per lifetime or at regular 5-yearly intervals, with or without vaccination of young females at age 15 years, assuming 70% coverage for both screening and vaccination. We also predicted cross-sectional cancer incidence each year to the year 2050 for a range of strategies. We found that strategies involving vaccination would be cost-effective at CVGs of US

Evaluation of primary HPV-DNA testing in relation to visual inspection methods for cervical cancer screening in rural China: an epidemiologic and cost-effectiveness modelling study

50-54 or less, but at CVGs >

Cervical cancer screening in Australia: modelled evaluation of the impact of changing the recommended interval from two to three years.

54, screening-only strategies would be more cost-effective. If vaccination of young cohorts is combined with two rounds of careHPV screening for women aged 30-59 years in 2012 and 2027, a predicted indicative 33% reduction in cervical cancer incidence by 2030 would be sustained until 2050, with incidence rates decreasing thereafter. In conclusion, taking into account estimated vaccine delivery costs (for 3 doses), a per-dose HPV vaccine cost of approximately <

Is expanding HPV vaccination programs to include school-aged boys likely to be value-for-money: a cost-utility analysis in a country with an existing school-girl program

9-14 would be required for strategies involving vaccination to be cost-effective. Overall, combined screening and vaccination approaches are required to maximise outcomes in rural China.

Will cervical screening remain cost-effective in women offered the next generation nonavalent HPV vaccine? Results for four developed countries.

BackgroundA new lower-cost rapid-throughput human papillomavirus (HPV) test (careHPV, Qiagen, Gaithersburg, USA) has been shown to have high sensitivity for the detection of high grade cervical intraepithelial neoplasia.MethodsWe assessed the outcomes and cost-effectiveness of careHPV screening in rural China, compared to visual inspection with acetic acid, when used alone (VIA) or in combination with Lugols iodine (VIA/VILI). Using data on sexual behaviour, test accuracy, diagnostic practices and costs from studies performed in rural China, we estimated the cost-effectiveness ratio (CER) and associated lifetime outcomes for once-lifetime and twice-lifetime screening strategies, and for routine screening at 5-yearly, 10-yearly and IARC-recommended intervals. The optimal age range for once-lifetime screening was also assessed.ResultsFor all strategies, the relative ordering of test technologies in reducing cervical cancer incidence and mortality was VIA (least effective); VIA/VILI; careHPV@1.0 pg/ml and careHPV@0.5 pg/ml (most effective). For once-lifetime strategies, maximum effectiveness was achieved if screening occurred between 35-50 years. Assuming a participation rate of ~70%, once-lifetime screening at age 35 years would reduce cancer mortality by 8% (for VIA) to 12% (for careHPV@0.5) over the long term, with a CER of US

Cost effectiveness of human papillomavirus test of cure after treatment for cervical intraepithelial neoplasia in England: economic analysis from NHS Sentinel Sites Study

557 (for VIA) to