This thesis is based on the following publications, which are referred to in the text by their Roman numerals.
I Lönnberg S, Leinonen M, Malila N, Anttila A. Validation of histological diagnoses in a national cervical screening register. Acta Oncol 2012;51:37-44.
II Lönnberg S, Anttila A, Kotaniemi-Talonen L, Kujari H, Melkko H, Granroth G, Vornanen M, Pietiläinen T, Sankila A, Arola J, Luostarinen T, Nieminen P.
Low proportion of false-negative smears in the Finnish program for cervical cancer screening. Cancer Epidemiol Biomarkers Prev 2010;19:381-7.
III Lönnberg S, Nieminen P, Kotaniemi-Talonen L, Kujari H, Melkko H, Granroth G, Vornanen M, Pietiläinen T, Arola J, Tarkkanen J, Luostarinen T, Anttila A. Large performance variation does not affect outcome in the Finnish cervical cancer screening programme. Cytopathol 2012;23:172-80.
IV Lönnberg S, Ahti Anttila, Luostarinen T, Nieminen P. Age-specific effective-ness of the Finnish cervical cancer screening programme. Cancer Epidemiol Biomarkers Prev 2012;21:1354-61.
V Lönnberg S, Nieminen P, Luostarinen T, Anttila A. Mortality audit of the Finnish cervical cancer screening programme. Int J Cancer 2012. doi:
10.1002/ijc.27844.
These publications are printed or reprinted here with permission from the copy-right holders.
4 aBBreviations
AGC-NOS atypical glandular cells – not otherwise specified AIS adenocarcinoma in situ
ASC-H atypical squamous cells – high-grade cannot be ruled out ASC-US atypical squamous cells – undetermined significance CIN1-3 cervical intraepithelial neoplasia, grade 1–3
CIN1-3+ CIN1-3 or worse
CIN3/AIS CIN3 or adenocarcinoma in situ ENCR European Network of Cancer Registries FCR Finnish Cancer Registry (or Register)
HDR Care Registers for Social Welfare and Health Care (formerly known as the Hospital Discharge Register)
HPV human papillomavirus hrHPV high-risk HPV
HSIL high-grade squamous intraepithelial lesion ICC invasive cervical cancer
ICD-10 International Classification of Diseases – 10th edition
ICD-O-3 International Classification of Diseases for Oncology – 3rd edition LSIL low-grade squamous intraepithelial lesion
MSR Mass Screening Registry (or Register)
NHS National Health Service (British health service provider) NOS not otherwise specified
NPV negative predictive value Pap I–V Papanicolaou class I–V
Pap smear cytological smear stained with the Papanicolaou method PPV positive predictive value
SCC squamous cell carcinoma (of the cervix)
THL Terveyden ja Hyvinvoinnin Laitos (Finland’s National Institute of Health and Welfare)
WHO World Health Organization
5 introduCtion
Cervical cancer screening via sampling of cells directly from the cervix, endocervix, and vagina has over the past half-century proved to be a very effective way of pre-venting the development of invasive cervical disease. The detection of abnormal cells in cervical scrapings or pap smears and subsequent diagnostic confirmation by colposcopy allow the excision of lesions at risk of becoming malignant. Cervi-cal cancer has several properties that make it particularly suitable for screening.
It usually develops via premalignant lesions in squamous or glandular epithelial cells visible in the transformation zone and the junction between these two dif-ferent epithelia. The transformation zone and junction is visible at younger ages at the ectocervix surface. At older ages, because of the metaplastic process, the junction often withdraws into the endocervical canal and may not be visible, even if still accessible for sampling. Hence, direct sampling of the potentially abnormal exfoliated cells can usually be performed without invasive procedures. Crucially, cervical cancer develops from a long-lasting and treatable premalignant phase that is suitable for detection by cytology and related histology.
Despite these advantages, the effectiveness of screening programmes has been widely variable. In some settings, large reductions in both incidence and mortal-ity of cervical cancer have been achieved, but in many cases impacts have been disappointingly low or even absent (IARC 2005, Anttila et al. 2009, Arbyn et al.
2009b). In order for the beneficial effects of screening to materialise, the entire chain from screening coverage to quality of treatment and follow-up has to be carefully controlled and optimised (EC 2003, IARC 2005, Arbyn et al. 2008a).
Comprehensive quality assurance for the screening process is possible only in the context of the organised and population-based screening programme. The quality of an individually tailored or opportunistic screening service can be excellent but is usually not consistently so and in any case remains very difficult to monitor, evaluate, and hence improve.
Comprehensive quality assurance for a screening programme can be viewed as comprising both monitoring and evaluation. Monitoring includes the tracking of cross-sectional performance indicators – for instance, as specified in the European guidelines – but also outcome-based longitudinal indicators such as interval cancer rates are needed (Arbyn et al. 2008a). The derivation of outcome indicators requires the linkage of screening and cancer registers and the construction of screening his-tory for all cancers – in other words, an audit of cervical cancer cases. A complete audit also entails review of both cytological screening tests and any histological slides, preferably with controls for reduced subjective evaluation bias. However, there are
crucial questions related to the optimisation of a screening programme that cannot be addressed with information derived from monitoring alone (for example the appropriate screening ages and intervals in a particular population); hence, in ad-dition to continuous monitoring of a programme, it is necessary that there also be periodic evaluation studies performed with a cohort–control or case–control design.
The ideal, then, is an organised population-based screening programme with quality assurance at every step in the screening chain; regular audits of all incident cancer cases; and evaluation of efficacy, effectiveness, benefit/harm ratio, and cost (Sasieni and Cuzick 2001, Arbyn et al. 2008a). Such a programme will continuously produce information about possible barriers to optimal impact and allow dynamic responses to changes in the quality of component functions or in the risk profile of the targeted population (Andrae and Smith 1999).
The objective of this work was to develop and pilot components of quality as-surance for integration into the cervical cancer screening programme and in the process to gain knowledge of the barriers to effectiveness and areas showing po-tential for improvement.