Cervical screening in HPV-vaccinated populations

Cervical screening with cytology has been the basis for substantial reductions in cervical cancer incidence and mortality in most high-income countries over the last few decades. More recently, there have been two key, parallel developments which have prompted a major re-consideration of cervical screening. The first is the emergence of evidence on the improved sensitivity of human papillomavirus (HPV) DNA testing compared to cytology, and the second is the large-scale deployment of prophylactic vaccination against HPV. A key challenge to be overcome before HPV screening could be introduced into national cervical screening programs was the specificity of an infection, for detection of precancerous lesions. This has been done in three ways: (1) by considering the appropriate age for starting HPV screening (30 years in unvaccinated populations and 25 years in populations with mature vaccination programs and high vaccine uptake) and the appropriate screening interval; (2) via development of clinical HPV tests, which are (by design) not as sensitive to low viral loads; and (3) by introducing effective triaging for HPV-positive women, which further risk-stratifies women before referral for diagnostic evaluation. This review discusses these major developments and describes how the benefits of HPV screening are being optimized in both unvaccinated and vaccinated populations

Impact of the National Cervical Screening Programme in New Zealand by age: analysis of cervical cancer trends 1985-2013 in all women and in Māori women

Background New Zealand is an example of a country with a well-established cytology-based screening program. New Zealand’s National Cervical Screening Programme (NCSP) commenced in 1990, and recommends three-yearly cytology-based screening for women aged 20–69 years. In 2018, the NCSP will transition to five-yearly HPV-based screening for women aged 25–69 years. The aim of this study was to assess the impact of the program to date in different groups, to provide a benchmark for the new program. Methods Analysis of cervical cancer trends in New Zealand by age and ethnicity over the period 1985–2013, and by morphology over the period 1997–2013, using data from the New Zealand Cancer Registry was conducted. Results The overall incidence of cervical cancer was 56% (95% CI 51–60%) lower in 2009–2013 than in 1985–1989, and significant reductions were observed in women aged 25–49, 50–69, and 70 + years. Relative reductions in cervical cancer were very similar for Māori and non-Māori women aged 25–49 (50% in Māori; 52% in non-Māori) and 50–69 years (65% in Māori; 69% in non-Māori). In contrast, incidence appeared to increase after around 1996 in women aged 20–24. The increasing trend was significant for women aged 20–24 overall and for non-Māori women (p < 0.01 in both cases). Conclusion There have been substantial reductions in cervical cancer among women aged 25 + years in New Zealand since the inception of the NCSP, and these reductions are similar in Māori and non-Māori women. Cervical cancer incidence among women 20–24 years has not declined since the NCSP began, and appears to be increasing.NZ MOHNZ MO

Participation in Cervical Screening by Older Asian and Middle Eastern Migrants in New South Wales, Australia

Background: There is little information on the detailed patterns of cervical screening uptake in older migrant women in Australia. This linkage study was performed to assess cervical screen-ing participation in older migrants.Methods: We linked year 2000-2001 records for 14,228 Middle Eastern/Asian-born women 40-64 years of age, and an age and area matched random sample of 13,939 Australian-born wom-en in the New South Wales (NSW) Admitted Patients Data Collection (APDC), which records country of birth, to screening register records. Screening behaviour after 1st July 2001 was as-sessed in women without a recorded prior cervical abnormalityResults: Compared to Australian-born women, women born in South Central Asia had a low-er screening participation rate (odds ratio for being screened at least once within a 3 year period 0.78, 95% CI 0.70-0.88). However, participation appeared relatively higher (17%-25%) in women born in the Middle East or other parts of Asia. Screening increased with increasing socioeconom-ic status (SES) in Australian-born women, but this trend was not observed in the migrant wom-en. When we broadly corrected for hysterectomy, the apparent excess of screening in women from the Middle East and other parts of Asia was substantially eliminated and in contrast, the apparent deficiency in screening in women from South Central Asia increased.Conclusions: Older women from the Middle East, and North East and South East Asian countries appeared to have similar overall screening participation to that of Australian-born women. Women from South Central Asia appeared less likely than Australian-born women to participate in cervical screening at the recommended interval

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

Background Cervical 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. Methods An 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). Results Shifting 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. Conclusion Relative 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

Vulvar cancer in high-income countries: Increasing burden of disease

The aim of this study was to assess trends in the age-specific incidence of vulvar cancer in 13 high-income countries satisfying a priori conditions regarding the availability of cancer registry data over a 20-year period; these were Canada, the United States, nine European countries, Australia and Japan. Five-yearly incidence and population at risk were obtained from the International Agency for Research on Cancer's Cancer Incidence in Five Continents for the years 1988-1992 (Volume 7) to 2003-2007 (Volume 10). The 5-yearly average percent change (AvPC) over the period and standardised rate ratios (SRRs) for 2003-2007 versus 1988-1992 were used to assess changes in the age-standardised incidence rates of vulvar cancer for all ages, and for <60 years and 60+ years. During the study period, the 5-yearly AvPC across the 13 countries increased by 4.6% (p = 0.005) in women of all ages, and 11.6% (p = 0.02) in those <60 years. No change was observed in women aged 60+ years (5-yearly AvPC = 0.1%, p = 0.94). The SRR for 2003-2007 versus 1988-1992 was significantly elevated in women <60 years of age (SRR = 1.38, 95% CI: 1.30-1.46), but not in women of 60+ years (SRR = 1.01, 95% CI: 0.97-1.05). The increase in incidence in women <60 years of age drove a significant increase in the overall SRR in women of all ages (SRR = 1.14, 95% CI: 1.11-1.18). Some differences in the specific findings at the individual country level were observed. The findings are consistent with changing sexual behaviours and increasing levels of exposure to human papillomavirus (HPV) in cohorts born around/after about 1950, but younger cohorts offered HPV vaccination are likely to receive some protection against developing vulvar cancer in the future

A revision of sexual mixing matrices in models of sexually transmitted infection

Two sexual mixing matrices previously used in models of sexually transmitted infections (STIs) are intended to calculate the probability of sexual interaction between age groups and sexual behaviour subgroups. When these matrices are used to specify multiple criteria for how people select sexual partners (such as age group and sexual behaviour class), their conditional probability structure means that they have in practice been prone to misuse. We constructed revised mixing matrices that incorporate a corrected conditional probability structure and then used one of them to examine the effect of this revision on population modelling of STIs. Using a dynamic model of human papillomavirus (HPV) transmission as an example, we examined changes to estimates of HPV prevalence and the relative reduction in age-standardised HPV incidence after the commencement of publicly funded HPV vaccination in Australia. When all other model specifications were left unchanged, the revised mixing matrix initially led to estimates of age-specific oncogenic HPV prevalence that were up to 11% higher than our previous models at certain ages. After re-calibrating the model by modifying unobservable parameters characterising HPV natural history, the revised mixing matrix yielded similar estimates to our previous models, predicting that vaccination would lead to relative HPV incidence reductions of 43% and 85% by 2010 and 2050, respectively, compared with 43% and 86% using the unrevised mixing matrix formulation. Our revised mixing matrix offers a rigorous alternative to commonly used mixing matrices, which can be used to reliably and explicitly accommodate conditional probabilities, with appropriate re-calibration of unobservable model parameter

Quantifying the impact of dissimilar HPV vaccination uptake among Manitoban school girls by ethnicity using a transmission dynamic model

BACKGROUND: Gardasil, a human papillomavirus (HPV) vaccine, began among grade 6 girls in Manitoba, Canada in 2008. In Manitoba, there is evidence that First Nations, Metis, and Inuit women (FNMI) have higher HPV prevalence, lower invasive cervical cancer (ICC) screening, and higher ICC incidence than all other Manitoban (AOM) women. We developed a mathematical model to assess the plausible impact of unequal vaccination coverage among school girls on future cervical cancer incidence. METHODS: We fit model estimated HPV prevalence and ICC incidence to corresponding empirical estimates. We used the fitted model to evaluate the impact of varying levels of vaccination uptake by FNMI status on future ICC incidence, assuming cervical screening uptake among FNMI and AOM women remained unchanged. RESULTS: Depending on vaccination coverage, estimated ICC incidence by 2059 ranged from 15% to 68% lower than if there were no vaccination. The level of cross-ethnic sexual mixing influenced the impact that vaccination rates among FNMI has on ICC incidence among AOM, and vice versa. The same level of AOM vaccination could result in ICC incidence that differs by up to 10%, depending on the level of FNMI vaccination. Similarly, the same level of FNMI vaccination could result in ICC incidence that differs by almost 40%, depending on the level of AOM vaccination. CONCLUSIONS: If we are unable to equalize vaccination uptake among all school girls, policy makers should prepare for higher levels of cervical cancer than would occur under equal vaccination uptak

Patterns of care and emergency presentations for people with non-small cell lung cancer in New South Wales, Australia: A population-based study

Introduction Little is known about population-wide emergency presentations and patterns of care for people diagnosed with non-small cell lung cancer (NSCLC) in Australia. We examined patients’ characteristics associated with presenting to an emergency department around the time of diagnosis (“emergency presenters”), and receiving anti-cancer treatment within 12 months of diagnosis. Materials and Methods Participants in the 45 and Up Study who were newly diagnosed with NSCLC during 2006–2010 were included. We used linked data from population-wide health databases including Medicare and pharmaceutical claims, inpatient hospitalisations and emergency department presentations to follow participants to June 2014. Patients’ characteristics associated with being an emergency presenter and receiving any anti-cancer treatment were examined. Results A total of 647 NSCLC cases were included (58.6% male, median age 73 years). Emergency presenters (34.5% of cases) were more likely to have a high Charlson comorbidity index score, be an ex-smoker who had quit in the past 15 years and to be diagnosed with distant metastases. Almost all patients had visited their general practitioner ≥3 times in the 6 months prior to diagnosis. Nearly one-third (29.5%) of patients did not receive any anti-cancer treatment, however, there were no differences between emergency and non-emergency presenters in the likelihood of receiving treatment. Those less likely to be treated were older, had no private health insurance, and had unknown stage disease recorded. Conclusion Our results indicate the difficulties in diagnosing lung cancer at an early stage and inequities in NSCLC treatment. Future research should address opportunities to diagnose lung cancer earlier and to optimise treatment pathways

Estimating the Cost-Effectiveness of Lung Cancer Screening with Low-Dose Computed Tomography for High-Risk Smokers in Australia

Introduction Health economic evaluations of lung cancer screening with low-dose computed tomography (LDCT) that are underpinned by clinical outcomes are relatively few. Methods We assessed the cost-effectiveness of LDCT lung screening in Australia by applying Australian cost and survival data to the outcomes observed in the U.S. National Lung Screening Trial (NLST), in which a 20% lung cancer mortality benefit was demonstrated for three rounds of annual screening among high-risk smokers age 55 to 74 years. Screening-related costs were estimated from Medicare Benefits Schedule reimbursement rates (2015), lung cancer diagnosis and treatment costs from a 2012 Australian hospital–based study, lung cancer survival rates from the New South Wales Cancer Registry (2005–2009), and other-cause mortality from Australian life tables weighted by smoking status. The health utility outcomes, screening participation rates, and lung cancer rates were those observed in the NLST. Incremental cost effectiveness ratios (ICER) were calculated for a 10-year time horizon. Results The cost-effectiveness of LDCT lung screening was estimated at AU$138,000 (80$84,700–AU$353,000)/life-year gained and AU$233,000 (80% confidence interval: AU$128,000–AU$1,110,000)/quality-adjusted life year (QALY) gained. The ICER was more favorable when LDCT screening impact on all-cause mortality was considered, even when the costs of incidental findings were also estimated in sensitivity analyses: AU$157,000/QALY gained. This can be compared to an indicative willingness-to-pay threshold in Australia of AU$30,000 to AU$50,000/QALY. Conclusions LDCT lung screening using NLST selection and implementation criteria is unlikely to be cost-effective in Australia. Future economic evaluations should consider alternative screening eligibility criteria, intervals, nodule management, the impact and cost of new therapies, investigations of incidental findings, and incorporation of smoking cessation interventions

Hormonal contraceptive use and smoking as risk factors for high-grade cervical intraepithelial neoplasia in unvaccinated women aged 30–44 years: A case-control study in New South Wales, Australia

Background Human papillomavirus (HPV) vaccines protect against HPV types 16/18, but do not eliminate the need to detect pre-cancerous lesions. Australian women vaccinated as teenage girls are now entering their mid-thirties. Since other oncogenic HPV types have been shown to be more prevalent in women ≥30 years old, understanding high grade cervical lesions in older women is still important. Hormonal contraceptives (HC) and smoking are recognised cofactors for the development of pre-malignant lesions. Methods 886 cases with cervical intraepithelial neoplasia (CIN) 2/3 and 3636 controls with normal cytology were recruited from the Pap Test Register of NSW, Australia. All women were aged 30–44 years. Conditional logistic regression was used to quantify the relationship of HC and smoking to CIN 2/3 adjusted for various factors. Results Current-users of HC were at higher risk for CIN 2/3 than never-users [odds ratio (OR) = 1.50, 95%CI = 1.03–2.17] and risk increased with increasing duration of use [ORs:1.13 (0.73–1.75), 1.51 (1.00–2.72), 1.82 (1.22–2.72) for <10, 10–14, ≥15 years of use; p-trend = 0.04]. Ex-users had risks similar to never-users (OR 1.08, 95%CI = 0.75–1.57) regardless of duration of use. Current smoking was significantly associated with CIN 2/3 (OR = 1.43, 95%CI = 1.14–1.80) and risk increased with increasing number of cigarettes/day (p-trend = 0.02). Among ex-smokers, the risk of CIN 2/3 decreased with increasing time since quitting (p-trend = 0.04). Conclusions In this benchmark study, current, long term users of HC and current smokers of ≥5 cigarettes/day were each at increased risk of developing CIN 2/3. Findings support smoking cessation in relation to decreasing the risk of pre-cancerous lesions and reinforce the continuing need for cervical screening for cancer prevention in vaccinated and unvaccinated populations