Karen Canfell

The predicted effect of changes in cervical screening practice in the UK: results from a modelling study.

In 2003, the National Health Service Cervical Screening Programme (NHSCSP) announced that its screening interval would be reduced to 3 years in women aged 25–49 and fixed at 5 years in those aged 50–64, and that women under 25 years will no longer be invited for screening. In order to assess these and possible further changes to cervical screening practice in the UK, we constructed a mathematical model of cervical HPV infection, cervical intraepithelial neoplasia and invasive cervical cancer, and of UK age-specific screening coverage rates, screening intervals and treatment efficacy. The predicted cumulative lifetime incidence of invasive cervical cancer in the UK is 1.70% in the absence of screening and 0.77% with pre-2003 screening practice. A reduction in lifetime incidence to 0.63% is predicted following the implementation of the 2003 NHSCSP recommendations, which represents a 63% reduction compared to incidence rates in the UK population if it were unscreened. The model suggests that, after the implementation of the 2003 recommendations, increasing the sensitivity of the screening test regime from its current average value of 56 to 90% would further reduce the cumulative lifetime incidence of invasive cervical cancer to 0.46%. Alternatively, extending screening to women aged 65–79 years would further reduce the lifetime incidence to 0.56%. Screening women aged 20–25 years would have minimal impact, with the cumulative lifetime incidence decreasing from 0.63 to 0.61%. In conclusion, the study supports the 2003 recommendations for changes to cervical screening intervals.

The burden of cervical cancer in China: Synthesis of the evidence

The burden of cervical cancer in China has not been characterized in detail. We reviewed cervical cancer data from national mortality surveys and registries, and conducted a meta‐analysis to estimate the prevalence of high‐grade lesions (HSIL) and high‐risk human papillomavirus (HR‐HPV) infections in rural Shanxi Province. We found that a national survey in the 1970s estimated age‐standardized cervical cancer mortality rates as ∼15 and ∼83/100,000 women nationally and in Xiangyuan, Shanxi; but the latest survey (2004–2005) found much lower rates of ∼3 and ∼7/100,000, respectively. IARC registries record age‐standardized cervical cancer incidence in China as <5/100,000 (1998–2002); but the five registry sites cover <2% of the population, and the gross domestic product per capita at each of the registry sites is higher than Chinas average (by a factor ranging from 1.3 to 3.9). The pooled estimate of the prevalence of HSIL and HR‐HPV in women aged 30–54 years in Shanxi was 3.7%(95%CI:2.7–4.8%) and 17.2%(95%CI:13.1–21.3%), respectively. Based on a feasible range informed by the incidence data for China and other unscreened populations, the predicted indicative annual number of new cervical cancer cases nationally, in the absence of any intervention, ranges from ∼27,000 to 130,000 (2010) to 42,000 to 187,000 (2050). In conclusion, recent data suggest comparatively low rates of cervical cancer incidence in China, which may be partly explained by the location of registry sites in higher socioeconomic status areas. However, the evidence is consistent with considerable heterogeneity within China, with a higher disease burden in some rural areas such as Shanxi. Therefore, the lower reported rates of cervical cancer in China should be interpreted cautiously.

Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study

Summary.  Background:  Current use of menopausal hormone therapy (HT) increases the risk of venous thromboembolism (VTE) and the formulations used may affect risk.

Injectable and oral contraceptive use and cancers of the breast, cervix, ovary, and endometrium in black South African women: case-control study.

A case-control study conducted in South Africa provides new estimates of the risk of specific cancers of the female reproductive system associated with use of injectable and oral contraceptives.

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 >