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Cervical cancer prevention: studies on outcome of cervical screening and on management of abnormal cytology findings
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background Screening by cytology has been highly effective in reducing the incidence and mortality from squamous invasive cervical cancer (ICC), but the effectiveness is less established regarding non-squamous ICC and regarding women above screening ages and below 30 years of age. Cervical cancer still occurs despite the presence of an organised screening programme. A substantial proportion of screened women with ICC are reported to have had previous abnormal cytology findings. The significance of negative cytology with limited evaluation is not quite determined, the most effective management of women with low-grade abnormalities is controversial, and evaluation of long-term effect of different treatment methods is limited.

Aims To identify possible areas of improvements in the prevention of cervical cancer by evaluating the effectiveness of the Swedish cervical screening programme, and by exploring risk factors for ICC in the cytological screening histories and in the management of women with abnormal cytology findings.

Methods The screening histories of all ICC cases in Sweden 1999-2001 (n=1230) and of five population-based control women per case were reviewed, using data from the Swedish Cancer Registry, the national population register, the Swedish national cervical screening quality register, histopathological reports and questionnaires to clinicians. The risk of cervical cancer according to screening histories 0.5-6.5 years before cancer diagnosis was estimated as odds ratios (ORs) in logistic regression models with 95% confidence interval (CI) (Paper I). Risk related to different cytological reports was assessed in women below 67 years of age with cytology (n=572, n=3569) in Paper II. The initial follow-up of women with abnormal or unsatisfactory cytology reports (n=159, n=258) was evaluated in Paper III, and further investigation and treatment of abnormalities (n=143 cases, n=176 controls) in Paper IV.

Results The cancer cases were above screening ages (31%), had not been screened according to recommendations (33%), had negative cytology (23%), or had previous positive screening tests (13%). No screening within the recommended interval increased the risk of squamous (OR 2.97, 95% CI 2.51-3.50) as well as non-squamous cancer (OR 1.59, 95% CI 1.20-2.11), and increased the risk in all ages. Negative cytology with partially obscuring factors and unsatisfactory cytology increased the risk of subsequent early stage ICC. All cytological abnormalities increased the risk of ICC, and women with glandular atypia or atypia in cells of uncertain origin carried a particularly high risk (OR 11.69, 95% CI 7.02-19.46). After a low-grade squamous abnormal smear finding, further investigation with biopsy was more effective than repeated cytology (OR 0.46, 95% CI 0.24-0.89). Lack of biopsy increased the risk in women with both low-grade and high-grade squamous abnormalities. Neither repeat cytology, nor biopsy, decreased the risk in women with glandular atypia or atypia in cells of uncertain origin. Treatment decreased the risk, even when the biopsy before treatment was negative or showed low-grade atypia only. Ablative therapy was less effective than excision and laser conisation was the most effective therapy.

Conclusions Improved adherence to screening recommendations and including older women at increased risk in the programme would have significant cancer preventive gains. Women with negative cytology with limited evaluation and with unsatisfactory cytology may need further evaluation. Assessment with biopsy should be recommended for women with low-grade as well as high-grade squamous abnormalities. The diagnosing of precancer lesions and the identification of women in need of treatment warrant improvements, in particular in cases of glandular or “other” atypia in cytology. Treatment techniques need further evaluation.

Place, publisher, year, edition, pages
Umeå: Umeå university , 2011. , 81 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1402
Keyword [en]
Cervical cancer, screening programme, effectiveness, risk factors, cytological screening history, management abnormal Pap smear, treatment, nationwide population-based case-control study
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Epidemiology
Identifiers
URN: urn:nbn:se:umu:diva-39862ISBN: 978-91-7459-150-7 (print)OAI: oai:DiVA.org:umu-39862DiVA: diva2:396727
Public defence
2011-03-04, Bergasalen, Byggnad 27, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2011-02-11 Created: 2011-02-10 Last updated: 2011-02-14Bibliographically approved
List of papers
1. Screening-preventable cervical cancer risks: evidence from a nationwide audit in Sweden
Open this publication in new window or tab >>Screening-preventable cervical cancer risks: evidence from a nationwide audit in Sweden
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2008 (English)In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 100, no 9, 622-629 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The effectiveness of cervical cancer screening programs differs widely in different populations. The reasons for these differences are unclear. Routine and comprehensive audits have been proposed as an ethically required component of screening. We performed a nationwide audit of the effectiveness of the Swedish cervical cancer screening program.

METHODS: We identified all invasive cervical cancer cases that were diagnosed in Sweden from January 1, 1999, through December 31, 2001, and had been reported to the Swedish Cancer Registry (n = 1230 cases). We verified the diagnoses by histopathologic rereview and matched each case subject to five (population-based) age-matched control subjects who were identified from the National Population Register. The Pap smear screening histories for case and control subjects were reviewed for a 6-year period using the National Cervical Cancer Screening Register, which contains data on essentially all relevant cytological and histological diagnoses in Sweden. Odds ratios (ORs), and their 95% confidence intervals (CIs), of cervical cancer according to screening history were calculated in conditional logistic regression models. All statistical tests were two-sided.

RESULTS: Women who had not had a Pap smear within the recommended screening interval had higher risk of cervical cancer than women who had been screened (OR = 2.52, 95% CI = 2.19 to 2.91). This risk was similarly increased for all age groups (P(homogeneity) = .96). The risk for non-squamous cell cervical cancers (OR = 1.59, 95% CI = 1.20 to 2.11) was also increased. Women who had not had a Pap smear within the recommended screening interval had a particularly high risk of advanced cancers (OR = 4.82, 95% CI = 3.61 to 6.44). Among women who had been screened within the recommended interval, those with abnormal Pap smears had a higher risk of cervical cancer than those with normal smears (OR = 7.55, 95% CI = 5.88 to 9.69) and constituted 11.5% of all women with cervical cancer.

CONCLUSIONS: Nonadherence to screening intervals was the major reason for cervical cancer morbidity. The screening program was equally effective for women of all ages and was also effective against non-squamous cancers.

Identifiers
urn:nbn:se:umu:diva-37044 (URN)10.1093/jnci/djn099 (DOI)18445828 (PubMedID)
Available from: 2010-10-19 Created: 2010-10-19 Last updated: 2017-12-12Bibliographically approved
2. Risk of invasive cervical cancer in relation to cytologic results in the screening history: a population‐based case‐control study
Open this publication in new window or tab >>Risk of invasive cervical cancer in relation to cytologic results in the screening history: a population‐based case‐control study
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(English)Manuscript (preprint) (Other academic)
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Epidemiology
Identifiers
urn:nbn:se:umu:diva-39849 (URN)
Available from: 2011-02-10 Created: 2011-02-10 Last updated: 2011-04-01Bibliographically approved
3. Risk of invasive cervical cancer in relation to management of abnormal Pap smear results
Open this publication in new window or tab >>Risk of invasive cervical cancer in relation to management of abnormal Pap smear results
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2009 (English)In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 201, no 2, 188.e1-188.e7 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: We sought to evaluate the management of women with abnormal cytology in terms of subsequent risk of invasive cervical cancer.

STUDY DESIGN: The screening histories of all invasive cervical cancer cases diagnosed in Sweden 1999-2001 and of 5 population-based controls per case were reviewed. In all, 159 patients and 258 control subjects aged < 67 years had an abnormal smear result 0.5-6.5 years prior to cancer diagnosis. The cervical cancer risk was estimated in relation to management by calculating odds ratios.

RESULTS: Histologic assessment of low-grade squamous abnormalities strongly reduced the risk compared to repeated cytology (odds ratio, 0.46; 95% confidence interval, 0.24-0.89). Delaying histologic assessment was also associated with a higher risk (odds ratio, 5.65; 95% confidence interval, 1.39-23.05). After high-grade squamous atypia, absence of any cytologic or histologic specimen was a major determinant of cancer risk (odds ratio, 12.52; 95% confidence interval, 1.42-infinitive).

CONCLUSION: For adequate protection against invasive cervical cancer, further assessment with histology must be recommended also for women with low-grade squamous abnormalities.

Keyword
cervical cancer risk; histologic assessment; management of abnormal Pap smear results; population-based case control study; repeated cytology
Identifiers
urn:nbn:se:umu:diva-37043 (URN)10.1016/j.ajog.2009.04.006 (DOI)19560117 (PubMedID)
Available from: 2010-10-19 Created: 2010-10-19 Last updated: 2017-12-12Bibliographically approved
4. Risk of invasive cervical cancer in relation to clinical investigation and treatment after abnormal cytology: a population-based case-control study
Open this publication in new window or tab >>Risk of invasive cervical cancer in relation to clinical investigation and treatment after abnormal cytology: a population-based case-control study
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2011 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 129, 1450-1458 p.Article in journal (Refereed) Published
Abstract [en]

A substantial proportion of women with cervical cancer that have participated in cervical screening have a history of an abnormal cytology result. Our objective was to assess the impact of histological investigation and treatment of women with abnormal cytology on the subsequent risk of invasive cervical cancer. All invasive cervical cancer cases in Sweden 1999-2001 and five population-based control women per case were investigated. Clinical investigations and treatment were analysed in case women (N = 143) and control women (N = 176) below 67 with abnormal cytology results 0.5-6.5 years before the cases' diagnosis. Cervical cancer risk in relation to investigation [histology or not, punch biopsy, cervical curettage or cone/large loop excision of the transformation zone (LLETZ)], and treatment (treatment or not, excisional or ablative) was estimated as odds ratios (ORs) using logistic regression. Absence of histological assessment was associated with increased cancer risk, both after low-grade [OR 2.37; 95% confidence intervals (CI): 1.27-4.43] and high-grade squamous atypia (8.26; 2.37-28.8). Among women with histology, absence of treatment was associated with increased cancer risk (3.68; 1.53-8.84), also when biopsy showed low-grade atypia or normal findings (3.57; 1.18-10.8). Ablative therapy associated with increased risk compared with excisional (3.82; 1.01-14.4), and laser conisation associated with decreased risk compared with LLETZ (0.06; 0.01-0.36). In conclusion, low-grade as well as high-grade squamous atypical cytology results may warrant histological investigation, treatment reduced cancer risk even when histology was negative or showed low-grade atypia indicating a need for improvements in the diagnosis of high-grade lesions, and laser conisation was the most effective treatment.

Place, publisher, year, edition, pages
Malden: Wiley-Blackwell, 2011
Keyword
abnormal Pap smear results, cervical cancer risk, clinical investigation, treatment, population-based case-control study
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Epidemiology
Identifiers
urn:nbn:se:umu:diva-39828 (URN)10.1002/ijc.25749 (DOI)000293245800021 ()21064110 (PubMedID)
External cooperation:
Available from: 2011-02-10 Created: 2011-02-10 Last updated: 2017-12-11Bibliographically approved

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