Kate T. Simms

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

A next generation nonavalent human papillomavirus (HPV) vaccine (“HPV9 vaccine”) is being introduced in several countries. The aims of this study were to evaluate whether cervical screening will remain cost‐effective in cohorts offered nonavalent vaccines and if so, to characterize the optimal number of screening tests. We used a dynamic model of HPV vaccination and cervical screening to evaluate the cost‐effectiveness of strategies involving varying numbers of primary HPV tests per lifetime for cohorts offered the nonavalent vaccine as 12 year‐olds. For each of four countries—the USA, New Zealand (NZ), Australia and England—we considered local factors including vaccine uptake rates (USA/NZ uptake ∼50%; Australia/England uptake >70%), attributable fractions of HPV9‐included types, demographic factors, costs and indicative willingness‐to‐pay (WTP) thresholds. Extensive probabilistic sensitivity analysis was performed. We found that, in the USA, four screens per lifetime was the most likely scenario, with 34% probability of being optimal at WTP US

Primary HPV testing versus cytology-based cervical screening in women in Australia vaccinated for HPV and unvaccinated: effectiveness and economic assessment for the National Cervical Screening Program

50,000/LYS, increasing to 84% probability at US

Effectiveness Modelling and Economic Evaluation of Primary HPV Screening for Cervical Cancer Prevention in New Zealand.

100,000/LYS. In New Zealand, five screens per lifetime was the most likely scenario, with 100% probability of being optimal at NZ

Impact of HPV sample self-collection for underscreened women in the renewed Cervical Screening Program

42,000/LYS, given the assumptions used. In Australia, two screens per lifetime was the most likely scenario, with 62% probability of being optimal at AU

Cost-effectiveness of the next generation nonavalent human papillomavirus vaccine in the context of primary human papillomavirus screening in Australia: a comparative modelling analysis

50,000/LYS. In England, four screens per lifetime was the most likely scenario, with 32% probability of being optimal at GB£20,000/LYS, increasing to 96% probability at GB£30,000/LYS. We conclude that some cervical screening will remain cost‐effective, even in countries with high vaccination coverage. However, the optimal number of screens may vary between countries.

Projected future impact of HPV vaccination and primary HPV screening on cervical cancer rates from 2017–2035: Example from Australia

BACKGROUND Australias National Cervical Screening Program currently recommends cytological screening every 2 years for women aged 18-69 years. Human papillomavirus (HPV) vaccination was implemented in 2007 with high population coverage, and falls in high-grade lesions in young women have been reported extensively. This decline prompted a major review of the National Cervical Screening Program and new clinical management guidelines, for which we undertook this analysis. METHODS We did effectiveness modelling and an economic assessment of potential new screening strategies, using a model of HPV transmission, vaccination, natural history, and cervical screening. First, we evaluated 132 screening strategies, including those based on cytology and primary HPV testing. Second, after a recommendation was made to adopt primary HPV screening with partial genotyping and direct referral to colposcopy of women positive for HPV16/18, we evaluated the final effect of HPV screening after incorporating new clinical guidelines for women positive for HPV. Both evaluations considered both unvaccinated and vaccinated cohorts. FINDINGS Strategies entailing HPV testing every 5 years and either partial genotyping for HPV16/18 or cytological co-testing were the most effective. One of the most effective and cost-effective strategies comprised primary HPV screening with referral of women positive for oncogenic HPV16/18 direct to colposcopy, with reflex cytological triage for women with other oncogenic types and direct referral for those in this group with high-grade cytological findings. After incorporating detailed clinical guidelines recommendations, this strategy is predicted to reduce cervical cancer incidence and mortality by 31% and 36%, respectively, in unvaccinated cohorts, and by 24% and 29%, respectively, in cohorts offered vaccination. Furthermore, this strategy is predicted to reduce costs by up to 19% for unvaccinated cohorts and 26% for cohorts offered vaccination, compared with the current programme. INTERPRETATION Primary HPV screening every 5 years with partial genotyping is predicted to be substantially more effective and potentially cost-saving compared with the current cytology-based screening programme undertaken every 2 years. These findings underpin the decision to transition to primary HPV screening with partial genotyping in the Australian National Cervical Screening Program, which will occur in May, 2017. FUNDING Department of Health, Australia.

How will transitioning from cytology to HPV testing change the balance between the benefits and harms of cervical cancer screening? Estimates of the impact on cervical cancer, treatment rates and adverse obstetric outcomes in Australia, a high vaccination coverage country

Background New Zealand (NZ) is considering transitioning from 3-yearly cervical cytology screening in women 20–69 years (current practice) to primary HPV screening. We evaluated HPV-based screening in both HPV-unvaccinated women and cohorts offered HPV vaccination in New Zealand (vaccination coverage ~50%). Methods A complex model of HPV transmission, vaccination, cervical screening, and invasive cervical cancer was extensively validated against national population-based datasets. Sixteen potential strategies for HPV screening were considered. Results Most primary HPV strategies were more effective than current practice, for both unvaccinated women and cohorts offered vaccination. The optimal strategy for both groups was 5-yearly HPV screening in women aged 25–69 years with partial genotyping for HPV 16/18 and referral to colposcopy, and cytological triage of other oncogenic types. This is predicted to reduce cervical cancer incidence and mortality by a further 12–16% and to save 4–13% annually in program costs (excluding overheads). The findings are sensitive to assumptions about future adherence to initiating screening at 25 years. Conclusion Primary HPV screening with partial genotyping would be more effective and less costly than the current cytology-based screening program, in both unvaccinated women and cohorts offered vaccination. These findings have been considered in a review of cervical screening in NZ.

The projected timeframe until cervical cancer elimination in Australia: a modelling study

Objectives: In 2017, the National Cervical Screening Program in Australia will transition to 5‐yearly primary HPV screening for all women, irrespective of human papillomavirus (HPV) vaccination status. As an adjunct to the mainstream program, HPV testing on self‐collected samples will be offered under practitioner supervision to all unscreened and underscreened women aged 30–74 years. We quantified how different screening decisions affect the future risk of cervical cancer.

Cost-effectiveness estimates: the need for complete reporting – Authors' reply

BACKGROUND First generation bivalent and quadrivalent human papillomavirus (HPV) vaccines have been introduced in most developed countries. A next generation nonavalent vaccine (HPV9) has become available, just as many countries are considering transitioning from cytology-based to HPV-based cervical screening. A key driver for the cost-effectiveness of HPV9 will be a reduction in screen-detected abnormalities and surveillance tests. We aimed to evaluate the cost-effectiveness of HPV9 in Australia, a country with HPV vaccination of both sexes that is transitioning to 5-yearly HPV-based screening. METHODS We used Policy1-Cervix and HPV-ADVISE-two dynamic models of HPV transmission, vaccination, and cervical screening-to estimate the cost-effectiveness of HPV9 versus quadrivalent vaccine (HPV4), assuming lifelong vaccine protection, two vaccine doses, and that additional costs were incurred in girls only. Policy1-Cervix was used to estimate the lifetime risk of cervical cancer diagnosis and death. Probabilistic sensitivity analysis of the cost-effectiveness outcomes was done with both models, and results are presented as the median and 10th to 90th percentiles of simulation runs (referred to as 80% uncertainty intervals [UIs]). FINDINGS Compared with cytology-based screening, HPV screening is predicted to reduce lifetime risk of cervical cancer diagnosis by 18% and of death by 20%, even in unvaccinated cohorts. Under base-case assumptions (lifelong protection, full efficacy at two doses), HPV4 will provide a further reduction in diagnosis of 54% and in death of 53% and HPV9 will provide a further reduction in both diagnosis and death of 11%, compared with cytology-based screening in unvaccinated cohorts. For HPV9 to remain a cost-effective alternative to HPV4, the incremental cost per dose in girls should not exceed a median of AUS

Transitioning from cytology-based screening to HPV-based screening at longer intervals: implications for resource use

35·99 (80% UI 28·47-41·18) with Policy1-Cervix or AUS