<![CDATA[Costs and benefits of combined programs of screening and vaccination]]>

Dr. Pekka Nieminen started noting that the aim of preventive interventions (screening, vaccination and information in the cervical cancer context) is to reduce the disease burden. For Finland, this means inviting every five years all 1.3 M women between the ages of 30 to 60 years to organized screening. Annually 180.000 organized screening visits are made by 72% of the invited women. The visits result in colposcopy referrals (1.1%) and CIN2+ diagnoses (0.4%). Together with 280.000 opportunistic screening visits, especially in young women between ages 15 to 25 years, this results in approximately 3000 CIN treatments annually [1]. The very intensive Pap-screening seems to have reached its performance limits since it has been unable to tackle the 1st cervical cancer incidence peak in 35 year-old women, and expectations for HPV DNA– based screening and prophylactic vaccination are great. For example, the successful Scottish vaccination program with >90% coverage has significantly reduced CIN findings in young women. However, also, the positive predictive values of screening and colposcopy for CIN2+ or high-grade findings have concomitantly reduced in the vaccinated populations from 77% to 66% and 74% to 67%, respectively – even at the lower quality assurance level [2, 3].

Thus, there is a need to model the integration of HPV vaccination and screening programs. In Finland this has been based on a dynamic transmission model and population-based registry data on HPV disease occurrence [16]. In addition to providing better screening algorithms to tackle the 2nd cervical cancer incidence peak in 60 year-old women the modelling results will help in the integration of HPV vaccination and screening.

Combining girls-only or gender-neutral vaccination even with rather conservative screening algorithms not only saves 15-20 M€ but reduces the number of quality adjusted lifeyears lost up to 10 and 20 times, respectively, as compared to no screening, and 2 and 4 times, respectively, compared to the present practice (figure 1).

The number of each dot, represents each strategy. Dots in blue represent no vaccination strategies; Dots in Grey: girls only vaccination at a 80% coverage; Dots in pink: girls and boys vaccination at a 80% coverage.
Under no vaccination and no screening programs (blue dot nº.1) the social costs of cervical cancer would be low (approx.11M€) but the QALY lost high (approx.5,000). Girls-only HPV vaccination (80% coverage), (grey dots 8, 9, 10) and gender-neutral HPv vaccination (80% coverage) in boys and girls, (pink dots 13, 14, 15) with a range of screening options would have similar costs but the number of QALYs lost would be 10 and 20 times lower.
Present practice: unsynchronised organised (30%) and opportunistic (70%) screening with 530.000 annual Pap-smears for a population of 1.3 M women.

Figure 1. Life-time costs and quality-adjusted life-yea (QALYs) lost for one 30,000 girls+30,000 boys birth cohort

References
1. Salo H, et al. Divergent coverage, frequency and costs of opportunistic and organized Pap testing in Finland. Int J Cancer, 2014. 135: p.204-213, 2014.
2. Palmer TJ,McFadden, Fm Ollock KGJ, et al. HPV immunisation and cervical screening— confirmation of changed performance of cytology as a screening test in immunised women: a retrospective population-based cohort study. Br J Cancer, 2016. 114:p.582-589.
3. Munro A, Gillespie C, Cotton S, et al. The impact of human papillomavirus type on colposcopy performance in women offered HPV immunisation in a catch-up vaccine programme: a two-centre observational study. BJOG, 2017 Jan 19. doi: 10.1111/1471-0528.14563.
4. Vänskä S, et al. Impact of vaccination on 14 high-risk HPV type infections: A mathematical modelling approach. PLoS One, 2013. 8:p.e72088.

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Pekka Nieminen, MD, PhD
University of Helsinki Central Hospital
Helsinki, Finland
pekka.nieminen@hus.fi

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