Cervical cancer in women under 30 years of age in Norway: a population-based cohort study.

BACKGROUND: We compared women with incident cervical cancer under the age of 30 with older women with regard to stage, morphology, screening history and cervical cancer mortality in a population-based cohort study. METHODS: We included data from the Cancer Registry of Norway. Incidence rates (per 100,000 women-years) were calculated and joinpoint regression was used to analyse trends. The Nelson-Aalen cumulative hazard function for risk of cervical cancer death during a 15-year follow-up was displayed. The hazard ratios (HRs) of cervical cancer mortality with 95% confidence intervals (CIs) were derived from Cox regression models. RESULTS: The incidence of cervical cancer in women under the age of 30 has almost tripled since the 1950s, with the steepest increase during 1955-80 (with an annual percentage change (APC) of 7.1% (95%CI 4.4-9.8)) and also an increase after 2004 (3.8% (95%CI -1.3-9.2)). Out of 21,160 women with cervical cancer (1953-2013), 5.3% were younger than 30 years. A lower proportion of younger women were diagnosed at more advanced stages and a slightly higher proportion were diagnosed with adenocarcinoma and adenosquamous carcinoma comparing women above 30 years. The cumulative risk of cervical cancer death was lower for patients under the age of 30. However, the difference between the age groups decreased over time. The overall adjusted HR of cervical cancer mortality was 0.69 (95% CI 0.58-0.82) in women diagnosed under the age of 30 compared to older women. CONCLUSION: There has been an increase in cervical cancer incidence in women under the age of 30. Cervical cancer in younger women was not more advanced at diagnosis compared to older women, and the cervical cancer mortality was lower.

Comparison of cytology and human papillomavirus-based primary testing in cervical screening programs in the Nordic countries.

OBJECTIVE: To compare primary test positivity in cytology and human papillomavirus-based screening between different Nordic cervical cancer screening programs using harmonized register data. METHODS: This study utilized individual-level data available in national databases in Finland, Iceland, Norway, and Sweden. Cervical test data from each country were converted to standard format and aggregated by calculating the number of test episodes for every test result for each calendar year and one-year age group and test method. Test positivity was estimated as the proportion of positive test results of all primary test episodes with a valid test result for "any positive" and "clearly positive" results. RESULTS: The age-adjusted rate ratio for any positive test results in primary human papillomavirus-based screening compared to cytology was 1.66 (95% CI 1.64-1.68). The age-adjusted rate ratio for clearly positive test results was 1.02 (95% CI 1.00-1.05). A decreasing rate ratio by age was seen in both any positive and clearly positive test results. Test positivity increased over time in Iceland, Norway, and Sweden but slightly decreased in Finland. CONCLUSIONS: The probability of any positive test result was higher in human papillomavirus testing than in primary cytology, even though the cross-sectional detection of a clearly positive test result was the same. Human papillomavirus testing can still lead to an improved longitudinal sensitivity through a larger number of follow-up tests and the opportunity to identify women with a persistent human papillomavirus infection. Further research on histologically verified precancerous lesions is needed in primary as well as repeat testing.

Adherence to international recommendations in the governance and organisation of Nordic cervical cancer screening programmes.

INTRODUCTION: Screening has been the primary reason for the decline in the incidence and mortality of cervical cancer in the Nordic countries since the beginning of screening in the 1960s. Recently, the incidence of cervical cancer has increased in the Nordic countries indicating the need to look closely at possibilities for further improvement in screening. This article provides an overview of cervical cancer screening programmes in the Nordic countries and whether the programmes adhere to international recommendations. MATERIALS AND METHODS: Relevant and unambiguous screening recommendations were extracted from applicable literature and classified into legal framework, governance, organisation, and monitoring and evaluation. The up-to-date status of screening programmes and adherence to selected recommendations was gathered from official documentation and co-authors representing cervical cancer screening programmes in all the Nordic countries. RESULTS: A total of 168 recommendations were extracted and 54 of them were considered to be unambiguous and relevant. Forty-nine recommendations were included after synthesising similar recommendations. All Nordic countries adhere to recommendations related to legal framework, but adherence was lower with recommendations related to governance and organisation of screening. Monitoring and evaluation are also areas where adherence to recommendations could be improved. CONCLUSIONS: The Nordic cervical cancer screening programmes have substantially decreased cancer burden despite not fully adhering to many of the recommendations. The presented gaps in adherence suggest that there is room for improvement in the screening programmes. Establishing clearer governance structures would still increase the ability to manage changes such as implementing HPV testing as the primary screening method or modifying the programme when HPV vaccinated cohorts of women enter the target age for screening.

NordScreen - an interactive tool for presenting cervical cancer screening indicators in the Nordic countries.

Introduction: Quality assurance and improvement of cancer screening programs require up-to-date monitoring systems and evidence-based indicators. National quality reports exist but the definition and calculation of indicators vary making comparisons between countries difficult. The aim is to stimulate collaborative research and quality improvements in screening through freely available, comparable and regularly updated quality indicators. The project currently includes data on cervical cancer screening but population-based screening programs for breast cancer and colorectal cancer may be included in the future. Material and methods: Through a network of Nordic and Baltic screening managers, population-based individual screening data from each country were converted to standard format in each collaborative center, aggregated by the same R program script and then uploaded to the NordScreen online platform. Registry data included all cervical tests except for Finland where only tests based on invitation are included. Results: The NordScreen collaboration has so far collated standardized indicators based on 32.8 million screening tests from four Nordic countries and Estonia. Interactive comparison of test coverage and distribution of women by number of tests are currently possible online. In 2016, the test coverage within a time interval of 5.5 years in the age group 30-64 year-olds was between 78 and 84% in Iceland, Norway and Sweden whereas 70% in Finland. The application allows users to choose indicator specifications interactively. Conclusions: NordScreen is a pilot model for comparable, reliable and accessible cross-country comparisons of cancer screening. Comparability between countries is enhanced by a uniform data structure and standardized calculations. The comparison of coverage rates to national figures shows that the methods used nationally and in the NordScreen project produce similar results.

Low proportion of unreported cervical treatments in the cancer registry of Norway between 1998 and 2013.

BACKGROUND: Accurate information about treatment is needed to evaluate cervical cancer prevention efforts. We studied completeness and validity of reporting cervical treatments in the Cancer Registry of Norway (CRN). MATERIAL AND METHODS: We identified 47,423 (92%) high-grade cervical dysplasia patients with and 3983 (8%) without recorded treatment in the CRN in 1998-2013. We linked the latter group to the nationwide registry of hospital discharges in 1998-2015. Of patients still without treatment records, we randomly selected 375 for review of their medical history. Factors predicting incomplete treatment records were assessed by multiple imputation and logistic regression. RESULTS: Registry linkage revealed that 10% (401/3983) of patients received treatment, usually conization, within one year of their initial high-grade dysplasia diagnosis. Of those, 11% (n = 44) were missing due to unreporting and 89% (n = 357) due to misclassification at the CRN. Of all cases in medical review, patients under active surveillance contributed almost 60% (223/375). Other reasons of being without recorded treatment were uncertain dysplasia diagnosis, invasive cancer or death. Coding error occurred in 19% (73/375) of randomly selected cases. CRN undercounted receipt of treatment by 38% (n = 1526) among patients without recorded treatment which translates into 97% overall completeness of treatment data. Incomplete treatment records were particularly associated with public laboratories, patients aged 40-54 years, and the latest study years. CONCLUSIONS: CRN holds accurate information on cervical treatments. Completeness and particularly validity can be further improved through the establishment of new internal routines and regular linkage to hospital discharges.

Results of delayed triage by HPV testing and cytology in the Norwegian Cervical Cancer Screening Programme.

BACKGROUND: High-risk human papilloma virus (hrHPV) testing was added to the cytology triage of women with equivocal screening smears in the Norwegian programme for cervical cancer screening in 2005. In this population-based observational before and after study we assessed the effect of changing the screening algorithm. MATERIAL AND METHODS: In periods before and after the change 75 852 and 66 616 women, respectively, were eligible for triage, i.e. they had smear results of unsatisfactory, atypical squamous cells of undetermined significance (ASC-US), or low-grade squamous intraepithelial lesion (LSIL) at routine screening. The triage was delayed as supplementary testing started six months after the initial screening. The groups were compared with respect to results of triage and later three-year cumulative incidence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). RESULTS: Before and after the change in the screening algorithm 5.2% (3964/75 852) and 8.1% (5417/66 616) of women, respectively, were referred to colposcopy. Among women referred to colposcopy cumulative incidence of CIN2+ (positive predictive value of referral) increased from 42.0% [95% confidence interval (CI): 40.3 - 43.7%] in the period with cytology only to 48.0% (95% CI 46.6 - 49.4%) after the start of HPV testing. For women recalled to ordinary screening the three-year cumulative incidence decreased from 2.7% (95% CI 2.5 - 2.9%) to 1.0% (95% CI 0.9 - 1.2%) during the same period. Among women with LSIL at routine screening and HPV testing in triage, 52.5% (1976/3766) were HPV positive. CONCLUSION: The new algorithm with HPV testing implemented in 2005 resulted in an increased rate of referral to colposcopy, but in a better risk stratification with respect to precancerous disease.

[Cervical cancer after 10 years of nationally coordinated screening]. / Livmorhalskreft etter ti års offentlig koordinert screening.

BACKGROUND: A cervical cancer screening programme has been operating on a national level since 1995. Women aged 25-69 years who have not had a Pap smear in the previous 3-year period, are recommended by letter to contact a doctor and have a smear taken. The aims of the programme are a more rational use of tests and to decrease the incidence and mortality of the disease. MATERIAL AND METHODS: Trends in incidence and mortality of cervical cancer are studied by data from the national cancer registry, which also collects data on individual smears. RESULTS: From the period 1990-94 to the period 2000-04 the age-adjusted incidence rate per 1,000, 000 person-years decreased from 127 to 95, the corresponding rate for squamous carcinomas decreased from 102 to 70. The age-adjusted mortality rate decreased from 38 to 25. Number of tests decreased from 542,666 in 1994 to 486 118 in 2004. The proportion of women aged 25-69 years who had a test taken during the last four years, increased from 72.4% in 1995 to 78.3% in 2004. INTERPRETATION: Implementation of a nationally coordinated cervical cancer screening programme has contributed to a favourable development of the disease (lower incidence and mortality) and a more rational use of tests. Continued efforts are needed to achieve the goals of the programme.

Pap smear screening in women under 30 in the Norwegian Coordinated Cervical Cancer Screening Program, with a comparison of immediate biopsy vs Pap smear triage of moderate dysplasia.

OBJECTIVE: Top provide population based estimates of Pap smear screening results among women under 30 and to compare the outcomes of 2 triage options for women under 30 with a moderate dysplastic Pap smear: immediate biopsy vs. Pap smear follow-up. STUDY DESIGN: All Pap smears, histologically verified cervical intraepithelial lesion (CIN) 2/3 and invasive cervical cancer in 1999-2002 from women in Norway under 30 in 2000-2002 were analyzed. Due to different triage recommendations in different laboratories, 836 women under 30 with a moderately dysplastic Pap smear were recommended for immediate biopsy, while 109 were recommended for a Pap smear within 6 months. Risk estimates for triage outcome were estimated by multinominal logistic regression. RESULTS: The prevalence of squamous intraepithelial lesion was highest around 20 years. The first moderate dysplasia was diagnosed at age 16, as was CIN 2/3. Of the women with Pap smear triage, one third were diagnosed with a CIN 2+ lesion, one third had a normal outcome, while the last third were in uncertain state 12 months later. Among those recommended for immediate biopsy, nearly 70% were diagnosed with a CIN 2+, thus having odds of 4.2 (95% CI 2.5-7.1) higher than did women with Pap smear triage of being diagnosed with CIN2+ 12 months later. CONCLUSION: The choice of triage has a profound impact on the proportion of young women diagnosed with CIN 2+ after a moderately dysplastic Pap smear.

Predicting CIN2+ when detecting HPV mRNA and DNA by PreTect HPV-proofer and consensus PCR: A 2-year follow-up of women with ASCUS or LSIL Pap smear.

It has been suggested that human papillomavirus (HPV) testing improves follow-up of atypical cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) in cervical cancer screening programs. To evaluate the prognostic value of including HPV testing as an adjunct to cytology, we carried out a 2-year follow-up study of 77 women with ASCUS or LSIL Papanicolaou (Pap) smear in the Norwegian Cervical Cancer Screening Program (NCCSP) for detection of histological cervical intraepithelial neoplasia (CIN) 2+. The study includes a comparison between viral mRNA and DNA detection. PreTect HPV-Proofer was used for HPV E6/E7 mRNA detection from the 5 high-risk types 16, 18, 31, 33 and 45, and Gp5+/6+ consensus PCR was used for HPV DNA detection. Twice as many women were positive for HPV DNA (54.6%) than for HPV mRNA (23.4%). PreTect HPV-Proofer and consensus PCR had a sensitivity of 85.7% (95% confidence interval [CI] = 42.1-99.6) for detecting CIN2+ during follow-up. The specificity was significantly higher for PreTect HPV-Proofer, 84.9% (95% CI = 73.9-92.5), than for consensus PCR, 50.0% (95% CI = 37.4-62.6). PreTect HPV-Proofer positive women were 69.8 times (95% CI = 4.3-1137.3) more likely to be diagnosed with CIN2+ within 2 years than PreTect HPV-Proofer negative women. Consensus PCR-positive women were 5.7 times (95% CI = 0.6-52.0) more likely to be diagnosed with CIN2+ within 2 years than PCR-negative women. With equal sensitivity and higher specificity than consensus PCR, the PreTect HPV-Proofer might offer an improvement for the triage of women with ASCUS or LSIL Pap smear.

CIN 2/3 and cervical cancer after an ASCUS pap smear. A 7-year, prospective study of the Norwegian population-based, coordinated screening program.

OBJECTIVE: To estimate the risk of being diagnosed with cervical intraepithelial neoplasia (CIN) 2/3 or invasive cervical cancer (ICC) based on diagnostic and screening procedures performed after a diagnosis of atypical squamous cells of undetermined significance (ASCUS) and to compare this risk to that in women with a normal Pap smears. STUDY DESIGN: A 7-year, prospective, cohort study was performed in the Norwegian population-based, coordinated screening program. After excluding women in the midst of follow-up of an abnormal Pap smear or with a history of CIN 2/3 or ICC, the study population consisted of women 25-69 years of age with a normal (n = 526,661) or ASCUS Pap smear (n = 10,037) in 1995-1996. Risk estimates were calculated by logistic and parametric survival regression. RESULTS: Within 7 years of an ASCUS smear, 1,017 women (10.1%) were diagnosed with CIN 2/3 and 62 (0.62%) with ICC. Women with an ASCUS index Pap smear had a relative risk of 15-30 of being diagnosed with histologically verified CIN 2/3 or ICC within the first 2 years of follow-up as compared to women with a normal index smear. In long-term follow-up, women with an ASCUS index smear followed by a normal smear, which cancelled further clinical follow-up, were at > 3.5 times higher risk of both CIN 2/3 and invasive cancer as compared to women with a normal index smear. CONCLUSION: Pap smear follow-up of women with an ASCUS smear does not identify all women at higher risk of CIN 2/3 and ICC. Other diagnostic procedures should be implemented to improve the screening program.