Reproducibility of colposcopy quality indicators-A survey among members of the European Federation for Colposcopy.

INTRODUCTION: Colposcopy is an important part of the diagnostic work-up of women with an abnormal cervical screening test as it is used to guide the collection of biopsies. Although quality assurance has been used in the evaluation of screening programs, not much is known about quality indicators for the diagnostics and treatment of screen-positive women. Therefore, the European Federation for Colposcopy developed quality indicators aiming to support colposcopy practice across Europe. We performed a survey of colposcopy cases to determine if the quality indicators are understandable, relevant, and reproducible. MATERIAL AND METHODS: We conducted a survey among all members of the European Federation for Colposcopy Quality and Standards Group from November 2022 to March 2023. Members were asked to collect information on a total of 17 quality indicators for 50 women who had been newly referred for colposcopy due to an abnormal screening test between January 1, 2020 to December 31, 2021. Results were reported descriptively. RESULTS: We included data on 609 cases from 12 members across Europe. The majority of the quality indicators were either achieved or within reach of the agreed standard, often due to few countries with outlying data. One quality indicator had very low performance, although stratified results indicated that two countries had different clinical management of the patient type thereby skewing the results. In addition, discrepancies between the number of cases included in each quality indicator raised concerns regarding potential misunderstanding of the quality indicator and its objective. CONCLUSIONS: Quality indicators on colposcopy must be understandable to those collecting data, highlighting the importance of validating quality indicators before data collection.

The quality of life of frequently vs. infrequently screened HPV vaccinated women.

PURPOSE: Cervical lesions caused by human papillomavirus (HPV) are related to decreased quality of life (QoL) of women. Also, cervical cancer (CC) screening can cause psychological adverse effects. It has been assumed that by decreasing the HPV-related disease burden, HPV vaccinations would increase the QoL. This study compares the effect of CC screening on QoL of HPV vaccinated women in two different screening protocols. METHODS: A total of 753 HPV16/18 vaccinated women were randomized to frequent (22/25/28 years of age) and infrequent (28 years of age) CC screening arms. QoL questionnaires (EQ VAS, RAND 36, amended CECA 10) were sent at the age of 28. RESULTS: Median EQ VAS scores were 80 (Q1-Q3 75-90) in both screening arms. Mean RAND 36 scores of frequently and infrequently screened women were 78.13/81.64 in Physical role functioning domain and, respectively, 77.93/80.18 in Pain, 69.10/69.12 in General Health, 54.67/53.61 in Energy, 83.72/85.11 in Social functioning, 69.53/69.68 in Emotional role functioning, and 68.16/69.29 in Emotional well-being domain. Among women with a self-reported history of Pap cytology abnormalities, overall mean scores of amended CECA 10 were 69.52/72.07, and among women with a self-reported history of genital warts, 60.09/66.73, respectively. CONCLUSION: There was no significant difference in the QoL of HPV vaccinated women between the two CC screening arms. Women were mostly satisfied with the screening experience despite the screening frequency. This information is important for the future screening program planning as we need to reach the best possible balance with screening benefits and harms. TRIAL REGISTRATION NUMBER: NCT02149030, date of registration 29/5/2014.

Added value of electrical impedance spectroscopy in adjunction of colposcopy: a prospective cohort study.

OBJECTIVE: To assess whether electrical impedance spectroscopy (EIS) as an adjunctive technology enhances the performance of colposcopy. DESIGN: Prospective cohort study. SETTING: University Hospital colposcopy clinic. PARTICIPANTS: Colposcopy with EIS for 647 women and conventional colposcopy for 962 women. INTERVENTIONS: Comparison of the performance of colposcopy by referral cervical cytology in two cohorts, with and without EIS as an adjunctive technology. OUTCOME MEASURES: Prevalence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), diagnostic testing accuracy to detect CIN2+ with and without EIS and their relative differences between cohorts. RESULTS: The prevalence of CIN2+ varied between the cohorts according to referral cytology: 17.0% after abnormal squamous cells of unknown significance referral cytology in EIS cohort and 9.1% in the reference cohort, 16.5% and 18.9% after low-grade squamous intraepithelial lesion (LSIL), 44.3% and 58.2% after atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (HSIL) (atypical squamous cells that cannot exclude HSIL), and 81.9% and 77.0% after HSIL cytology, respectively. Sensitivity to detect CIN2+ was higher in the EIS cohort, varying from 1.79 (95% CI 1.30 to 2.45) after LSIL referral cytology to 1.16 (95% CI 1.09 to 1.23) after HSIL referral cytology, with correspondingly lower specificity after any referral cytology. CONCLUSIONS: Colposcopy with EIS had overall higher sensitivity but lower specificity to detect CIN2+ than conventional colposcopy. CIN2+ prevalence rates were, however, not consistently higher in the EIS cohort, suggesting innate differences between the cohorts or truly lower detection rates of CIN2+ for EIS, highlighting the need for randomised controlled trials on the effectiveness of EIS.

Long-term risk of cancer among the first-degree relatives of epithelial ovarian cancer patients: A cohort study with 48 years of follow up.

INTRODUCTION: The long-term risk of cancer among first-degree relatives of ovarian cancer patients, especially their offspring, is of apparent clinical importance. Risks caused by known inherited factors such as BRCA1 or BRCA2 pathogenic variants are well established, but these account for only about 15% of ovarian cancer cases. Less is known about the possible familial risks of sporadic ovarian cancers. MATERIAL AND METHODS: Using registry data, we conducted a retrospective cohort study with a total of 6501 first-degree relatives of 559 epithelial ovarian cancer patients. We studied the occurrence of overall cancer and cancer in specific sites known or suspected to be associated with ovarian cancer (breast, cervix, colon, endometrium, lung and trachea, skin melanoma, ovary, pancreas, prostate, rectum, and stomach). RESULTS: The overall number of cancers was not increased among the first-degree relatives of epithelial ovarian cancer patients during the up to 48 years of follow up. Among female relatives, the standardized incidence ratio for ovarian cancer was 1.92 (95% CI 1.27-2.79), mostly explained by a 2.30-fold (95% CI 1.46-3.45) risk among the patients' sisters. There was a decreasing trend in the standardized incidence ratio for ovarian cancer among patients' sisters by increasing age of the index patient. CONCLUSIONS: In our study cohort, we did not observe an increase in the overall cancer risk among the first-degree relatives of epithelial ovarian cancer patients in comparison with the general population. The risk for ovarian cancer, however, was increased. Current recommendations suggest prophylactic removal of the fallopian tubes and ovaries only with identified inherited risk factors. Our results emphasize the role of genetic counseling and testing, particularly in young ovarian cancer patients and their close female relatives.

Overtreatment rate after immediate local excision of suspected cervical intraepithelial neoplasia: A prospective cohort study.

OBJECTIVE: The gold standard of cervical intraepithelial neoplasia (CIN) treatment is large loop excision of the transformation zone (LLETZ) after histopathological diagnosis from punch biopsies. In addition, treatment may be appropriate at initial colposcopy. Our objective was to study the applicability of immediate treatment strategy according to clinical parameters. METHODS: We conducted a prospective cohort study among patients referred to colposcopy at Helsinki University Hospital, Finland, between January 2014, and September 2018 (ISRCTN10933736). Patients treated with LLETZ, either after biopsies or immediately at initial colposcopy, were included. The main outcome measure was overtreatment (OT) rate defined as normal or low-grade histopathological findings in LLETZ specimen within both treatment groups. RESULTS: A total of 572 patients treated with LLETZ were included: 360 treated after biopsies and 212 treated immediately at initial colposcopy. When LLETZ was performed immediately after high-grade referral cytology and with colposcopic impression of high-grade disease, the overtreatment (OT) rate was 10.0% (95% CI 9.10 to 17.2), whereas when LLETZ was done after biopsy-confirmed high-grade lesions, the OT rate was 18.9% (95% CI 14.7 to 23.7), resulting in risk difference (RD) -8.91% (95% CI -16.0 to -1.82). Among HPV16/18 positive patients the OT rate was 8.22% (95% CI 3.08 to 17.0) for immediate treatment, resulting in RD of -10.7% (95% CI -18.3 to -3.04) compared to LLETZ after biopsies. CONCLUSIONS: Immediate LLETZ does not result in overtreatment when applied on selected cases, especially after high-grade referral cytology and when high-grade lesion is also colposcopically suspected.

Primary HPV screening for cervical cancer: Results after two screening rounds in a regional screening program in Finland.

INTRODUCTION: Since 2012, cervical cancer screening has been conducted with a primary high-risk human papillomavirus (hrHPV) test and conventional cytology triage in the city of Tampere, Finland. The women who were screened with the hrHPV test in 2012 were invited to participate in the second screening round in 2017. The aim of the present report was to compare the number of colposcopy referrals and the number of histological high-grade squamous intraepithelial lesion (HSIL)+ (cervical intraepithelial neoplasia [CIN2+]) lesions between the first and second screening rounds of women of a specific age group who were screened twice with the hrHPV test. MATERIAL AND METHODS: The primary hrHPV test used was the RealTime hrHPV PCR assay by Abbott. Women with a positive hrHPV test and cytology triage equal to or worse than low-grade squamous intraepithelial lesion or atypical glandular cells, favor neoplasia, were directly referred to colposcopy, whereas hrHPV-positive women with a negative or equivocal cytology triage were re-screened after approximately 12-16 months. hrHPV-negative women were scheduled for re-screening after 5 years. The present report focuses on the cohort of women who were screened twice with the hrHPV test, who were 35-55 years old in 2012, and 40-60 years old in 2017. RESULTS: In all, 8076 women were invited for HPV screening in 2012 and 8331 women were invited for the second round 5 years later, with attendance rates of 70% and 71%, respectively. Of the women who were screened in 2012, 4571 (69%) belonged to the 35- to 55-year age cohort. In 2017, 4807 (73%) of the women aged 40-60 years participated in the screening. In this cohort, 185 (4.0%) colposcopies were performed in the first screening round, compared with 139 (2.9%) in the second round, and the colposcopy rate was 29% smaller in the second round (P = .002). The number of histological HSIL+ cases was 38 (0.8%) during the first screening round and 29 (0.6%) during the second round (P = .220). CONCLUSIONS: In the setting of routine organized cervical cancer screening, the initially high colposcopy rate associated with primary HPV screening seems to level off at the second screening round in women who were screened twice with an hrHPV test.

The HPV test has similar sensitivity but more overdiagnosis than the Pap test--a randomised health services study on cervical cancer screening in Finland.

We compared test sensitivity (in terms of prevented cancers) and overdiagnosis (in terms of non-progressive pre-invasive lesions) between the human papillomavirus test (HPV test, Hybrid Capture 2) and the traditional Pap test in routine screening for cervical cancer. The design was a randomised (1:1) health services study in Finland with intake between 2003 and 2007. We estimated sensitivity by the incidence method within one screening round. Overdiagnosis was based on the rate of cervical intraepithelial Grade 3 (CIN3) lesions diagnosed at screen and during the following interval. Out of 203,788 randomised women 132,298 attended (65% in both study arms) and 600,753 person-years accumulated among attenders up to the end of 2010. In all attenders, 34 invasive cervical cancers and 288 CIN3 lesions were diagnosed at screen or during the following interval. The interval cancer incidence was 2.5/10(5) person-years (sensitivity 0.87) and 1.4 (sensitivity 0.93) in the HPV arm and Pap test arm, respectively. The rate of CIN3 lesions was 57.1 and 38.8, respectively. In conclusion, sensitivity of HPV testing was similar to that of Pap testing but caused more overdiagnosis. Therefore, implementation of HPV testing needs to be reconsidered especially in countries with well organised programmes.

Cervical cancer patterns with automation-assisted and conventional cytological screening: a randomized study.

The purpose was to evaluate alternative cytological screening methods in population-based screening for cervical cancer up to cancer incidence and mortality outcome. Automation-assisted screening was compared to conventional cytological screening in a randomized design. The study was based on follow-up of 503,391 women invited in the Finnish cervical cancer screening program during 1999-2003. The endpoints were incident cervical cancer, severe intraepithelial neoplasia and deaths from cervical cancer. One third of the women had been randomly allocated to automation-assisted screening and two thirds to conventional cytology. Information on cervical cancer and severe neoplasia were obtained through 1999-2007 from a linkage between screening and cancer registry files. There were altogether 3.2 million woman-years at risk, and the average follow-up time was 6.3 years. There was no difference in the risk of cervical cancer between the automation-assisted and conventional screening methods; the relative risk (RR) of cervical cancer between the study and control arm was 1.00 (95% confidence interval [CI] = 0.76-1.29) among all invited and 1.08 (95% CI = 0.76-1.51) among women who were test negative at entry. Comparing women who were test negative with nonscreened, RR of cervical cancer incidence was 0.26, 95% CI = 0.19-0.36 and of mortality 0.24 (0.13-0.43). Both methods were valid for screening. Because cervical cancer is rare in our country, we cannot rule out small differences between methods. Evidence on alternative methods for cervical cancer screening is increasing and it is thus feasible to evaluate new methods in large-scale population-based screening programs up to cancer outcome.

Intensified screening among high risk women within the organised screening programme for cervical cancer in Finland.

MATERIAL AND METHODS: Based on a five-year follow-up of 130 692 women who participated in the five-yearly organised screening in Finland in 1995, we estimated the risk for incident invasive cervical cancer and severe precancerous lesion for groups of women with different combinations of high-risk determinants at baseline. RESULTS: Compared to women with normal cytology and no symptoms at the index screen, the risk of developing invasive cervical cancer during the next screening interval was significantly elevated in women with abnormal cytology at baseline screen (RR 5.8, 95% CI 2.6-13.1); additionally, the risk of cervical intraepithelial neoplasia grade 3 (CIN3) lesions was even higher (RR 9.4, 95% CI 6.9-12.5), both results after removing respective screen detected cases at index screen. Among women with symptoms of vaginal bleeding or abnormal vaginal discharge but normal cytology the risk of invasive cervical cancer was increased but not significantly (RR 2.4, 95% CI 0.9-6.3) and the risk of CIN3 lesions was only slightly elevated (RR 1.5, 95% CI 0.95-2.4). In women less than 40 years of age, the risk of cervical cancer was 50% higher than in women 40 years or more in those with normal cytology and no symptoms, however not significantly. Symptoms indicated a similarly elevated risk for cancer in both age groups. After abnormal cytology there was a nine-fold risk for cancer in young women (under 40 years) and a six-fold risk in old women (40 years or more) when compared to women aged 40 or more with no symptoms and normal cytology. In young women CIN3 lesions were found in great excess, three times more often, compared to those aged 40 and over. DISCUSSION: In all, selective intensified screening for cervical cancer complementing the five-yearly unselective programme is feasible for women with abnormal cytological findings at an acceptable level of incremental cost.

Rate of cervical cancer, severe intraepithelial neoplasia, and adenocarcinoma in situ in primary HPV DNA screening with cytology triage: randomised study within organised screening programme.

OBJECTIVE: To assess the performance and impact of primary human papillomavirus (HPV) DNA screening with cytology triage compared with conventional cytology on cervical cancer and severe pre-cancerous lesions. DESIGN: Randomised trial. SETTING: Population based screening programme for cervical cancer in southern Finland in 2003-5. PARTICIPANTS: 58 076 women, aged 30-60, invited to the routine population based screening programme for cervical cancer. INTERVENTIONS: Primary HPV DNA test (hybrid capture II) with cytology triage if the result was positive or conventional cytological screening (reference). MAIN OUTCOME MEASURES: Rate of cervical cancer, cervical intraepithelial neoplasia (CIN) grade III, and adenocarcinoma in situ (as a composite outcome referred to as CIN III+) during 2003-7 through record linkage between files from the screening registry and the national cancer registry. RESULTS: In the HPV and conventional arms there were 95 600 and 95 700 woman years of follow-up and 76 and 53 cases of CIN III+, respectively (of which six and eight were cervical cancers). The relative rate of CIN III+ in the HPV arm versus the conventional arm was 1.44 (95% confidence interval 1.01 to 2.05) among all women invited for screening and 1.77 (1.16 to 2.74) among those who attended. Among women with a normal or negative test result, the relative rate of subsequent CIN III+ was 0.28 (0.04 to 1.17). The rate of cervical cancer between arms was 0.75 (0.25 to 2.16) among women invited for screening and 1.98 (0.52 to 9.38) among those who attended. CONCLUSIONS: When incorporated into a well established organised screening programme, primary HPV screening with cytology triage was more sensitive than conventional cytology in detecting CIN III+ lesions. The number of cases of cervical cancer was small, but considering the high probability of progression of CIN III the findings are of importance regarding cancer prevention. TRIAL REGISTRATION: Current Controlled Trials ISRCTN23885553.

Low proportion of false-negative smears in the Finnish program for cervical cancer screening.

BACKGROUND: We assessed the performance and validity of cytology in the Finnish screening program by considering high-grade neoplasia and cervical cancer (CIN3+) rates as detected in the program and by reevaluating cases observed after a negative screening test. METHODS: This retrospective study included 915 screen-detected CIN3+ cases and 421 cases observed after a negative screen. Randomized and blinded reevaluation of potential false-negative screening tests covered 345 archival case smears from women without a referral to colposcopy, as well as 689 control smears for estimating performance and validity measures. RESULTS: The false-negative rate at the cutoff of low-grade squamous intraepithelial lesion or worse was 35% (95% confidence interval, 30-40%). In the subpopulation with original screening result of Pap I, the false-negative rate was 23% (18-28%). Sensitivity of screening laboratory rereading for detecting low-grade lesions or worse as atypical was 75% (67-82%) and specificity 93% (91-94%). Reproducibility of specific cytologic diagnoses was only fair. False negatives constituted 11% of all CIN3+ diagnoses in the screened population; those false negatives with an original Pap I screening result constituted 5%. CONCLUSIONS: Although screen failures in the form of diagnostic false negatives occur within the Finnish screening program, their effect on cancer incidence is fairly small and cannot be readily decreased without sacrificing the high specificity of screening or without high incremental costs. Feedback for the screening laboratories is needed, however, to improve the reproducibility of cytologic diagnoses to optimize the burden of intensified follow-up and treatment of precancerous lesions.

Age-specific evaluation of primary human papillomavirus screening vs conventional cytology in a randomized setting.

BACKGROUND: Human papillomavirus (HPV) DNA testing has shown higher sensitivity than cytology for detecting cervical lesions, but it is uncertain whether the higher sensitivity is dependent on the age of the woman being screened. We compared the age-specific performance of primary HPV DNA screening with that of conventional cytology screening in the setting of an organized population-based cervical cancer screening program in Finland. METHODS: From January 1, 2003, to December 31, 2005, randomized invitations were sent to women aged 25-65 years for routine cervical cancer screening by primary high-risk HPV DNA testing (n = 54 207) with a Hybrid Capture 2 assay followed by cytology triage for women who were HPV DNA positive or by conventional cytology screening (n = 54 218). In both screening arms, cytology results of low-grade squamous intraepithelial lesion or worse triggered a referral for colposcopy. Relative rates (RRs) of detection to assess test sensitivity, specificity, and positive predictive values (PPVs) with 95% confidence intervals (CIs) were calculated for the histological endpoints of cervical intraepithelial neoplasia (CIN) grade 1 or higher (CIN 1+), CIN grade 2 or higher (CIN 2+), and CIN grade 3 or higher (CIN 3+). All statistical tests were two-sided. RESULTS: The overall frequency of colposcopy referrals was 1.2% in both screening arms. Women younger than 35 years were referred more often in the HPV DNA screening vs the conventional screening arm (RR = 1.27, 95% CI = 1.01 to 1.60). The prevalence of histologically confirmed CIN or cancer was 0.59% in the HPV DNA screening arm vs 0.43% in the conventional screening arm. The relative rates of detection for CIN 1, CIN 2, and CIN 3+ for HPV DNA screening with cytology triage vs conventional screening were 1.44 (95% CI = 0.99 to 2.10), 1.39 (95% CI = 1.03 to 1.88), and 1.22 (95% CI = 0.78 to 1.92), respectively. The specificity of the HPV DNA test with cytology triage was equal to that of conventional screening for all age groups (99.2% vs 99.1% for CIN 2+, P = .13). Among women aged 35 years or older, the HPV DNA test with cytology triage tended to have higher specificity than conventional screening. The PPVs for HPV DNA screening with cytology triage were consistently higher than those for conventional screening. In both screening arms, the test specificities increased with increasing age of the women being screening, whereas the highest PPVs were observed among the youngest women being screened. Overall, 7.2% of women in the HPV DNA screening arm vs 6.6% of women in the conventional screening arm were recommended for intensified follow-up, and the percentages were highest among 25- to 29-year-olds (21.9% vs 10.0%, respectively). CONCLUSIONS: Primary HPV DNA screening with cytology triage is more sensitive than conventional screening. Among women aged 35 years or older, primary HPV DNA screening with cytology triage is also more specific than conventional screening and decreases colposcopy referrals and follow-up tests.

Test positivity cutoff level of a high risk human papillomavirus test could be increased in routine cervical cancer screening.

We present data on test positivity, relative sensitivity, rates of detection and relative specificity for primary human papillomavirus (HPV) testing with different cutoff levels for test positivity, in comparison to conventional cytology. In 2003-2004, 18,438 women were screened primarily with Hybrid Capture 2 (HC 2) assay, a test for oncogenic HPV DNA, and 21,446 with conventional cytology within the organised screening programme in Finland. A cytological triage test was performed for the HPV positives. Women with cytology equal to low grade squamous intraepithelial lesion (LSIL) or worse were referred for colposcopy. The relative sensitivity measured as relative risk (RR) of any cervical intraepithelial neoplasia (CIN) or cancer was 1.58 for the HPV test at the relative light units (rlu) ratio cutoff 1.00, in comparison to cytology. With the cutoff 3.00, all CIN 2+ lesions were detected. With cutoff 10.00, 2 of the 22 CIN 3+ lesions were missed. Relative specificity for HPV screening for any CIN was 92.6% at cutoff 1.00, 94.6% at cutoff 3.00 and 96.3% at cutoff 10.00. For CIN 3+ specificity estimates for these cutoffs were 92.1%, 94.1% and 95.8%, respectively. Used for routine screening as the sole test, the HPV test cutoff can be increased from the level recommended for clinical use. With HC 2, the detection rate at rlu ratio cutoff 10.00 is still at the level of high-quality conventional screening. At that level, the false positive rate is reduced by about half and the specificity of the HPV test becomes equal to the average specificity of conventional cytology.

Prevalence of oncogenic human papillomavirus infection in an organised screening population in Finland.

A persistent high-risk human papillomavirus (hrHPV) infection is a necessary condition for developing a cervical intraepithelial neoplasia and cervical cancer. The viral aetiology in cervical carcinogenesis has stimulated attempts to use HPV DNA detection in cervical cancer screening. In Finland there is an ongoing study assessing the benefits of primary HPV DNA testing in the setting of centrally organised mass screening for cervical cancer. Here we present the age-specific prevalence of hrHPV infection and associated sociodemographic factors of 16,895 women aged 25-65 years attending the 5-yearly cervical cancer screening between years 2003 and 2004. The overall hrHPV prevalence rate was 7.5%. The peak prevalence at the age group of 25-29 was 24.1% decreasing steadily thereafter to approximately 2.9% in women aged 65 years. Young age and marital status were the main determinants for oncogenic HPV types. Our study confirms the inverse relationship between age and hrHPV prevalence reported in many developed countries. As our prevalence rates and hence background risk for cervical cancer are not lower than in other European countries, it is likely that our lowest cervical cancer burden in Europe is due to health care actions justifying the organised cervical cancer screening.

Screening with a primary human papillomavirus test does not increase detection of cervical cancer and intraepithelial neoplasia 3.

AIM: To determine cross-sectional validity of primary human papillomavirus (HPV) screening in comparison to cytological screening. METHODS: During 2003-2004, 61,149 women were individually randomised to screening with a test for oncogenic HPV DNA or to conventional cytological screening within the Finnish cervical screening programme. RESULTS: For HPV screening, cross-sectional relative sensitivity for cervical intraepithelial neoplasia (CIN) or cancer was 1.58 (95 % confidence interval 1.19-2.09) in comparison to cytology. At the level of CIN 3 or cancer no increase in relative sensitivity was observed. Cross-sectional specificity estimates for the screening arms were comparable, but the specificity of screening with sole HPV DNA test was clearly inferior. CONCLUSIONS: Primary HPV screening with cytology triage finds more CIN lesions compared to conventional screening but mild lesions are overrepresented. This is likely to result in overdiagnosis since most mild lesions are regressive.

Randomized evaluation trial on automation-assisted screening for cervical cancer: results after 777,000 invitations.

OBJECTIVES: New cervical screening methods have been developed. They seem to become accepted in routine use without randomized trials, within existing screening programmes. Our aim was to evaluate, in a randomized setting, the performance of automation-assisted cytological screening in routine use compared with conventional Papanicoalou (Pap) screening. SETTING: This prospective study was based on a 1:2 individually randomized design. Altogether 777,144 women were invited to attend the routine screening programme. RESULTS: Automation-assisted screening found more Pap class III (LSIL+) findings compared with conventional study arm, relative risk (RR) 1.08 (confidence interval 1.01-1.15). Also, detection rates of verified pre-cancers were more common in automation-assisted arm, RR 1.11 (1.02-1.21). CONCLUSIONS: Automation-assisted screening performed well compared with conventional screening. The difference was smaller than reported in non-randomized studies. A new technique may assume several years to reach the ultimate quality and can add costs without improving efficacy. Follow-up of prevented cervical cancers is required.

Significant variation in performance does not reflect the effectiveness of the cervical cancer screening programme in Finland.

AIM: To characterise the variation in performance indicators of the Finnish cervical screening programme by screening laboratory and to assess whether the performance affects cervical cancer incidence. METHODS: Cervical cancer screening data from 1999 to 2003 from six well-established laboratories were used to analyse rates for follow-up recommendations, referrals and histologically confirmed dysplastic lesions. Laboratory-specific cervical cancer incidences for 1954-2003 were assessed using the cancer registry files. RESULTS: Differences in follow-up recommendations were up to 3.1-fold and 2.2-fold in referrals; differences in the rates for CIN1, CIN2 and CIN3+ were up to 4.5-, 4.7-, and 1.5-fold, respectively. Pre-screening incidence rates for cervical cancer varied 1.5-fold by laboratory, with no major differences in the incidence trends since the onset of screening. CONCLUSION: The performance of a cervical screening programme differs by screening laboratory but does not materially affect the overall programme effectiveness. This leads to variation in cost-effectiveness and probably in avoidable adverse effects. In cervical cancer screening studies, the outcome should be selected as closely as possible to the true measure of programme effectiveness, prevented invasive cervical cancers and subsequent deaths.

Alternative technologies in cervical cancer screening: a randomised evaluation trial.

BACKGROUND: Cervical cancer screening programmes have markedly reduced the incidence and mortality rates of the disease. A substantial amount of deaths from the disease could be prevented further by organised screening programmes or improving currently running programmes. METHODS/DESIGN: We present here a randomised evaluation trial design integrated to the Finnish cervical cancer screening programme, in order to evaluate renewal of the programme using emerging technological alternatives. The main aim of the evaluation is to assess screening effectiveness, using subsequent cancers as the outcome and screen-detected pre-cancers as surrogates. For the time being, approximately 863,000 women have been allocated to automation-assisted cytology, human papillomavirus (HPV) DNA testing, or to conventional cytology within the organised screening programme. Follow-up results on subsequent cervical cancers will become available during 2007-2015. DISCUSSION: Large-scale randomised trials are useful to clarify effectiveness and cost-effectiveness issues of the most important technological alternatives in the screening programmes for cervical cancer.