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Objective: To compare the real-life screening outcomes after cytology was replaced by human papillomavirus (HPV) testing for women aged 60-64 years., Methods: Using the Danish national pathology register, we compared screening outcomes during two consecutive calendar periods, one where women were screened with cytology and one where most women were screened with HPV testing. Our primary outcomes were the proportions of women with positive test results, high-grade cervical intraepithelial neoplasia (CIN 2 or worse), and cervical cancer., Results: Women screened during the HPV testing period were more likely to have a positive screening test result than were women screened during the cytology period (relative proportion 2.80, 95% CI 2.65-2.96). The detection of CIN 2 or worse was also increased (relative proportion 1.54, 95% CI 1.31-1.80), whereas there was no increase in screen-detected cervical cancer diagnoses (relative proportion 1.27, 95% CI 0.76-2.12). Within the first 4 years after a negative screening test result, including 168,477 woman-years at risk after a negative screen result in the HPV period and 451,421 woman-years after a negative screen result in the cytology period, the risk of a cervical cancer diagnosis was approximately 4 per 100,000 woman-years and was similar for both screening tests (relative risk 0.99, 95% CI 0.41-2.35)., Conclusion: Human papillomavirus testing led to more positive screening test results and diagnoses of high-grade CIN lesions. Few women were diagnosed with cervical cancer after a negative screening test result., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Human Papillomavirus (HPV) genotyping has an increasingly important role in cervical cancer screening and vaccination monitoring, however, without an internationally agreed standard reference assay. The test results from the most widely used genotyping assays are read manually and hence prone to inter-observer variability. The reading of test results on the CLART HPV2 genotyping assay is, on the other hand, automated. The aim of our study was to directly compare the detection of HPV genotypes and high-grade cervical intraepithelial neoplasia (CIN) by CLART, Linear Array (LA), and Hybrid Capture 2 (HC2) using samples stored in SurePath., Methods: Residual material from 401 routine samples from women with abnormal cytology was tested by CLART, LA, and HC2 (ClinicalTrial.gov: NCT01671462, Ethical Committee approval: H-2012-070). Histological outcomes were ascertained by linkage to the Danish nation-wide Pathology Data Bank. For comparison of CLART and LA in terms of genotype detection, we calculated κ-coefficients, and proportions of overall and positive agreement. For comparison of CIN detection between CLART, LA, and HC2, we calculated the relative sensitivity and specificity for high-grade CIN., Results: The κ-coefficient for agreement in detection of genotypes 16, 18, 31, 33, 35, and 51 was ≥0.90 (overall agreement: 98-99%, positive agreement: 84-95%). The values were slightly lower, but still in the "substantial" range for genotypes 39, 45, 52, 56, 58, 59, and several low-risk genotypes. The relative sensitivity of CLART for ≥ CIN2 and ≥ CIN3 was not significantly lower than that of LA and HC2, although CLART showed a higher specificity than HC2., Conclusions: In Danish women with abnormal SurePath cytology, CLART and LA were highly comparable for detection of most high-risk and low-risk genotypes; and CLART's sensitivity for high-grade CIN was comparable to that of both LA and HC2.

Background: On the basis of a population-based cohort, we assessed the cancer risk, focusing on gynaecological cancers and pre-malignant lesions, among women with a previous tubal sterilization., Methods: Using the Danish Hospital Discharge Register we identified 65 232 women who had a tubal sterilization (1977-1993). The cohort was followed for cancer occurrence, and compared with the expected number based on the national cancer incidence rates., Results: The overall risk of ovarian cancer was decreased (standardized incidence ratio [SIR] = 0.82; 95% CI: 0.6, 1.0), and it was still decreased > or =10 years after the sterilization (SIR = 0.65; 95% CI: 0.4, 1.0). The rate of endometrial cancer was also decreased (SIR = 0.66; 95% CI: 0.5, 1.0), the risk continued being moderately reduced during follow-up, although it was not statistically significant., Conclusions: In this nationwide, population-based study we find that women with tubal sterilization have a decreased risk of subsequent development of ovarian cancer. As the protective effect is not decreasing with years of follow-up, our data do not support that 'screening' bias can explain the protective effect, but indicate that the sterilization itself may convey a reduction in risk. The same pattern is found for endometrial cancer, the association being less strong.

Non-progression and duration of preclinical neoplastic lesions of the cervix uteri were studied using screening data from a previously unscreened population, Maribo County, Denmark (1966-82). To estimate regression rates, the incidence of clinical cancer before the screening programme was related to the prevalence and incidence of preclinical lesions estimated from the detection rates of first smear and third and subsequent smears respectively. Duration was estimated from the time lag between the cumulative incidence of preclinical lesions and the combined cumulative incidence of clinical cancer and the estimated 'incidence of regression'. Of all preclinical lesions in women aged 25-50, 24% progressed, 39% regressed and 38% remained. Even if we assume no onset of preclinical lesions above age 50, we estimated that 48% of the preclinical lesions would not progress to clinical cancer in the women's lifetime. The estimated mean duration of preclinical lesions was 16 years. In Maribo County during the 1970s, the positive rate (1.6%) was low compared with current rates in several countries. We conclude that the detection of non-progressive lesions was outweighed by the prevention of clinical cancer.

The role of smoking and other risk factors for cervical neoplasia was investigated in a population-based case-control study of 586 women with histologically verified cervical squamous-cell carcinoma in situ (CIS), and 59 women with invasive squamous-cell cervical cancer from Copenhagen. Controls were randomly selected from the general female population using the computerized Danish Central Population Register. After adjustment for a variety of confounding variables, which were all significantly associated with CIS risk and included age, number of partners, proportion of sexually active life without barrier contraceptive use, years with intra-uterine devices, number of births, and age at first episode of genital warts (as a proxy measure for human papillomavirus exposure), current cigarette smoking was found to be significantly associated with CIS [adjusted relative risk (RR) = 2.4; 95% confidence interval (CI): 1.7-3.4]. Ex-smokers had a lower, but still significantly increased risk (RR = 1.6; 95% CI: 1.0-2.7). A dose-response relationship was present, especially for number of cigarettes smoked per day. In contrast, the crude estimates showed a weak association between invasive cervical cancer and smoking, which however disappeared after confounder control. The results of the present study support the hypothesis implicating smoking as a risk factor for CIS.

Possible risk factors for abnormal Papanicolaou smear were investigated in a population-based cross-sectional study. From Nuuk (Greenland) and Nykøbing Falster (Denmark), random samples of 800 women aged 20-39 years were drawn. Totals of 586 and 661 women were included in Greenland and Denmark, respectively. All women went through a personal interview, and had a gynecologic examination including a PAP smear and cervical swab for HPV analysis. A blood sample was taken for analysis of HSV type specific antibodies. Multiple sexual partners was the most important risk factor for abnormal cervical cytology (OR = 4.2). An infectious etiology was also indirectly supported by a relatively protective effect of barrier contraceptive methods (OR = 0.6). The simultaneous finding of HPV 16/18 as a significant risk factor (OR = 2.4) cannot be taken uncritically as support for a causal effect of this HPV type, since such a relationship between cytological changes of the cervix and HPV infection could also emerge if the positive PAP smear was not just a measure of intra-epithelial neoplasia but also an expression of the infection itself on the cervix.