BACKGROUND Danish women vaccinated with the 4-valent human papillomavirus (HPV) vaccine (HPV types: 6/11/16/18) at age 14 in 2008 reached screening age in 2017, allowing assessment of long-term effects on prevalence, persistence and incidence of HPV infections. AIM To examine the HPV status of cervical samples over time among women vaccinated as girls. METHODS Between February 2017 and February 2024, residual material from cytology-analysed samples collected through the ‘Trial23’ study, part of the national screening programme, was tested for HPV16/18 and non-vaccine high-risk (HR) HPV types. Prevalence in first, second and third samples, and persistence and incidence between samples were calculated. RESULTS Over 7 years, 8,659 women provided at least one sample, 5,835 at least two and 2,461 at least three. In 7,800 vaccinated women, HPV16/18 prevalence was 0.4% (95% confidence interval (CI): 0.2–0.5), 0.3% (95% CI: 0.1–0.4) and 0.2% (95% CI: 0.0–0.4) in three consecutive samples. Prevalence of non-vaccine HR HPV was 32% (95% CI: 31–33), 28% (95% CI: 27–29) and 31% (95% CI: 29–33). Persistence of HPV16/18 and non-vaccine HPV among vaccinated women was 40% and 53%. In adjusted analyses comparing vaccinated vs unvaccinated women, incidence was significantly lower for HPV16/18 (adjusted relative risk (aRR) < 0.10) while incidence of non-vaccine HR HPV types was higher (aRR: 1.66; 95% CI: 1.12–2.45). No significant difference was observed for persistence. CONCLUSION Our study provides real-world evidence of stable protection against HPV16/18 infections in women vaccinated as girls. Less intensive screening seems reasonable until women vaccinated with the 9-valent vaccine reach screening age, when screening should be reconsidered.

BACKGROUND:Danish women-who were HPV-vaccinated as girls-are now reaching an age where they are invited to cervical cancer screening. Because of their expected lower cervical cancer risk, we must reassess our screening strategies. We analyzed Danish HPV-vaccinated women's outcomes after the first screening test at age 23. METHODS AND FINDINGS:Our study was embedded in Danish routine cytology-based screening. We conducted an observational study and included women born in 1994, offered the 4-valent HPV vaccine at age 14, and subsequently invited to screening at age 23. Cervical cytology was used for diagnostics and clinical management. Residual material was HPV tested with Cobas® 4800/6800. The most severe histology diagnosis within 795 days of screening was found through linkage with the Danish National Pathology Register. We calculated the number of women undergoing follow-up (repeated testing and/or colposcopy) per detected cervical intraepithelial neoplasia (CIN2+). A total of 6021 women were screened; 92% were HPV-vaccinated; 12% had abnormal cytology; 35% were high-risk HPV-positive, including 0.9% HPV16/18 positive, and 20% had follow-up. In women that were cytology-abnormal and HPV-positive (Cyt+/HPV+), 610 (98.5%) had been followed up, and 138 CIN2+ cases were diagnosed, resulting in 4.4 (95% CI 3.9-5.2) women undergoing follow-up per detected CIN2+. In contrast to recommendations, 182 (12.2%) cytology-normal and HPV-positive (Cyt-/HPV+) women were followed up within 795 days, and 8 CIN2+ cases were found, resulting in 22.8 (95% CI 13.3-59.3) women undergoing follow-up per detected CIN2+. CONCLUSION:Overall, HPV prevalence was high in HPV-vaccinated women, but HPV16/18 had largely disappeared. In the large group of cytology-normal and HPV-positive women, 23 had been followed up per detected CIN2+ case. Our data indicated that primary HPV screening of young HPV-vaccinated women would require very effective triage methods to avoid an excessive follow-up burden. TRIAL REGISTRATION:Trial registration number: NCT0304955.

Objective. To evaluate the impact of a cervical cancer (CC) diagnosis on use of health care and prescription drugs. Methods. This population-based register-study included Danish women aged 23-59 years and diagnosed with CC in 2001-2005. Women with a cervical screening outcome were used as comparison group. We obtained number of contacts to general practitioners (GPs), hospitals, psychologists/psychiatrists and defined daily doses (DDD) of analgesic/psychotropic prescription drugs. A difference-in-differences-design was used to estimate effect of a CC diagnosis on health-care use from five-year periods before and after the diagnosis/screening outcome. Results. In total, 926 women with CC and 1,004,759 women without cancer were included. In five years following the date of CC diagnosis, CC patients had increased their use of GPs with 8.6 (95% CI 4.8-12.4) contacts more than women in the comparison group, and with 4.12 (95% CI 3.99-4.25) more hospital contacts. In contrast, use of psychologists/psychiatrists was low and largely unaffected by the CC diagnosis. For use of prescription drugs, analgesics increased with 80 (95% CI 60-100) DDD more in CC patients than in comparison women, and for psychotropics with 304 (95% CI 261-347) DDD more. Conclusions. A CC diagnosis was followed by an increase in use of GPs, hospitals, and analgesic/psychotropic prescription drugs, while use of psychologist/psychiatrist was largely unaffected. This pattern may indicate that pain/mental health concerns after CC either persisted or were alleviated by other means only. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

Vaccination against human papillomavirus (HPV) has been introduced as a public health initiative in many countries, including Denmark since October 2008. It is important to monitor postimplementation effectiveness of HPV-vaccination at the population-level. We studied HPV-prevalence after first invitation to screening at age 23 years in women offered the quadrivalent HPV-vaccine at the age of 14 years. Randomly selected screening samples from women born in 1994 in four out of five Danish regions were subjected to analysis for HPV in addition to routine cytology. Cobas4800 was used in all participating pathology departments. Data from a Danish prevaccination cross-sectional study using Hybrid Capture 2, and a Danish split-sample study using Cobas4800 were used for comparison. In the period from February 2017 to April 2019, 6233 screening samples from women born in 1994 were selected for HPV-analysis; 27 samples had no HPV-test and 3 samples had no HPV-diagnosis, leaving 6203 samples with an HPV-diagnosis. Prevalence of any high-risk (HR) HPV was 35%; only 0.9% were positive for vaccine HPV types 16/18 while the remaining 34% were positive for other HR HPV. When comparing with prevaccination prevalence data, HPV-16/18 decreased by 95%; RR = 0.05 (95% CI 0.04-0.06), while other HR HPV remained fairly constant; RR = 0.88 (95% CI 0.82-0.94) and RR = 0.95 (95% CI 0.88-1.03), respectively. One-third of women vaccinated as girls with the quadrivalent HPV-vaccine were HR HPV-positive at time of first invitation to screening. Vaccine HPV-types 16 and 18 were almost eliminated, while the prevalence of nonvaccine HR HPV-types remained constant.

The aim of this study was to assess whether negative psychological consequences of conization reported in questionnaire studies translated into increased use of the healthcare services that could relieve such symptoms. This was a population-based register study comparing women undergoing conization with a control group of women with normal cytology results. Data were derived from Danish registers. Using the difference-in-differences method, we measured contacts with general practitioners (GPs), hospitals, psychiatrist/psychologists, and use of anxiolytic and antidepressant prescription drugs over 5 years ‘before’ and ‘after’ the conization in the study group, and in comparable periods in the control group. During the ‘before’ period, women who later had a conization had greater contact with GPs and hospitals, and slightly more contact with psychiatrist/psychologists, than control women. In both groups, healthcare use increased significantly from the ‘before’ to the ‘after’ period. For contacts with GPs and hospitals, the increase was significantly larger for the conization group than for the control group, but this could be attributed to the standard postconization follow-up process. In the ‘before’ period, women who later had a conization used fewer drugs than women of the control-group, but their drug use increased similarly over time. The conization event did not result in an increased use of the healthcare services that could relieve potential negative side effects. However, women who underwent a conization seemed to constitute a select group as they already used GPs and hospitals more frequently, and anxiolytic and antidepressant drugs less frequently, than other women in the years ‘before’ the conization event.

IntroductionThe first birth cohorts of women offered human papillomavirus (HPV) vaccination as girls are now entering cervical screening. However, there is no international consensus on how to screen HPV vaccinated women. These women are better protected against cervical cancer and could therefore be offered less intensive screening. Primary HPV testing is more sensitive than cytology, allowing for a longer screening interval. The aim of Trial23 is to investigate if primary HPV testing with cytology triage of HPV positive samples is a reasonable screening scheme for women offered HPV vaccination as girls.MethodsTrial23 is a method study embedded in the existing cervical screening programme in four out of five Danish regions. Without affecting the screening programme, women born in 1994 are randomised to present screening with liquid-based cytology every third year (present programme arm) or present screening plus an HPV test (HPV arm). The study started 1 February 2017 and will run over three screening rounds corresponding to 7–8 years.AnalysesThe primary endpoint is cervical intraepithelial neoplasia grade 3 or above. The trial is undertaken as a non-inferiority study including intention-to-treat and per-protocol analyses. The potential effect of primary HPV screening with a 6-year interval will be calculated from the observed data.Ethics and disseminationThe study protocol has been submitted to the ethical committee and deemed a method study. All women are screened according to routine guidelines. The study will contribute new evidence on the future screening of HPV vaccinated birth cohorts of women. All results will be published in open-access journal.Trial registrationNCT03049553.

Introduction: Despite an intensive screening activity, the incidence of cervical cancer in Denmark has remained stable for the last 15years, while regional differences have increased. To search for explanations, we investigated possible weaknesses in the screening program.Material and methods: Data on the screen-targeted women were retrieved from Statistics Denmark. Data on screening activity were retrieved from the annual reports from 2009 to 2015 on quality of cervical screening. Coverage was calculated as proportion of screen-targeted women with at least one cytology sample within recommended time intervals. Insufficient follow-up was calculated as proportion of abnormal and unsatisfactory samples not followed up within recommended time intervals. Diagnostic distribution was calculated for samples with a satisfactory cytology diagnosis.Results: Coverage remained stable at 75%-76% during the study period. Annually, approximately 100,000 women are screened before they are eligible for invitation, and 600,000 invitations and reminders are issued resulting in screening of 200,000 women. In 2009, 21% of abnormal and unsatisfactory samples were not followed up within the recommended time interval; a proportion that had decreased to 15% in 2015. Overall, 11% of satisfactory samples with a cytology diagnosis were abnormal, but with surprising variation from 6% to 15% across regions.Discussion: The success of a screening program depends first of all on coverage and timely follow-up of abnormal findings. Our analysis indicated that the currently high incidence of cervical cancer in Denmark may partly be due to low screening coverage. Also worrisome is a high proportion of non-timely follow-up of abnormal findings. Innovative ways to improve coverage and follow-up are urgently needed.

We studied how representative cytologically abnormal women ("referral populations") are with respect to uncovering differences between human papillomavirus (HPV) assays in the primary screening where most women are cytologically normal.A total of 4997 women were tested with SurePath® cytology, and Hybrid Capture 2 (HC2), cobas, CLART and APTIMA HPV assays. Women with positive test results were offered a follow-up. For all detected HPV infections and HPV-positive high-grade cervical intraepithelial neoplasia (≥CIN2), we studied the distributions of assay-specific signal strengths in the baseline samples as documented by the assays' automatically generated reports. We calculated the likelihood of test result discordance as the proportion of HPV-positive samples that were not confirmed by all four assays.Median signal strengths for HPV infections were weaker in normal than abnormal cytology (P<.001, adjusted for women's age, multiple infections and the reason for taking the sample). For HC2, they were RLU/CO 11.0 (interquartile range, IQR: 3.3-52.8) vs 124.2 (IQR: 22.8-506.9), respectively; for cobas, Ct 33.5 (IQR: 29.6-37.5) vs 26.9 (IQR: 23.7-31.3), respectively; for APTIMA, S/CO 10.2 (IQR: 5.8-11.3) vs 11.1 (IQR: 9.4-15.5), respectively. Similar patterns were observed for HPV-positive ≥CIN2. The four HPV assays more frequently returned discordant test results in normal than in abnormal cytology. Relative frequency of discordance in detecting HPV infections was 0.39 (95% confidence interval: 0.33-0.48) for abnormal vs normal cytology.These data suggest that referral population studies, by not including sufficient numbers of cytology normal women, underestimate the differences between HPV assays that would become apparent in primary screening.

Self-sampling for human papillomavirus (HPV) offered to women who do not participate in cervical cancer screening is an increasingly popular method to increase screening coverage. The rationale behind self-sampling is that unscreened women harbour a high proportion of undetected precancer lesions. Here, we compare the cervical intraepithelial neoplasia grade 2 or worse (⩾CIN2) detection rate between non-attenders who participated in self-sampling and women attending routine screening. A total of 23 632 women who were qualified as non-attenders in the Copenhagen Region were invited for HPV-based self-sampling. Of these, 4824 women returned a self-sample, and HPV-positive women were referred for cytology and HPV co-testing as follow-up. The entire cohort and a reference cohort (3347 routinely screened women) were followed for histopathology confirmed ⩾CIN2. Odds ratio (OR) and the relative positive predictive value of ⩾CIN2 detection between the two populations were estimated. Women participating in self-sampling had a higher ⩾CIN2 detection than women undergoing routine cytology-based screening (OR=1.83, 95% CI: 1.21–2.77) and a similar detection as routinely screened women tested with cytology and HPV testing (OR=1.03, 95% CI: 0.75–1.40). The positive predictive value for ⩾CIN2 was higher in screening non-attenders than in routinely HPV- and cytology-screened screened women (36.5% vs 25.6%, respectively). Self-sampling offered to non-attenders showed higher detection rates for ⩾CIN2 than routine cytology-based screening, and similar detection rates as HPV and cytology co-testing. This reinforces the importance of self-sampling for screening non-attenders in organised cervical cancer screening.

In organized cervical screening programs, typically 25% of the invited women do not attend. The Copenhagen Self-sampling Initiative (CSi) aimed to gain experiences on participation among screening nonattenders in the Capital Region of Denmark. Here, we report on the effectiveness of different communication platforms used in the pilot with suggestions for strategies prior to a full-implementation. Moreover, an innovative approach using self-sampling brushes with unique radio frequency identification chips allowed for unprecedented levels patient identification safety. Nonattenders from the capital region of Denmark were identified via the organized national invitation module. Screening history was obtained via the nationwide pathology registry. Twenty-four thousand women were invited, and as an alternative to the regular communication platforms (letter and phone), women could request a home test via a mobile-friendly webpage. Instruction material and video-animation in several languages were made available online. Chi-square test was used to test differences. Out of all invited, 31.7% requested a home test, and 20% returned it to the laboratory. In addition, 10% were screened at the physician after receiving the invitation. Stratified by screening history, long-term unscreened women were less likely to participate than intermittently screened women (28% vs. 16%, p<0.001). Of all contacts received, 64% (63-65) came via letter, and 31% (95CI: 30-32%) via webpage/mobile-app. Self-sampling was well-accepted among nonattenders. Adopting modern technology-based platforms into the current organized screening program would serve as a convenient communication method between health authority and citizens, allowing easy access for the citizen and reducing the work load in administrating self-sampling approaches.What's new? Our implementation study is the first to evaluate opt-in self-sampling for 24,000 screening nonattenders, which can be basis for future routine implementation. Women could respond through a variety of communication channels (regular mail, phone and custom-made web/mobile-app). Our study utilized self-sampling brushes with a novel RFID-chip for secure patient-identification, eliminating inconveniences for the women to fill out forms on returning the brush and loss of brushes due to missing identification.

The Copenhagen Self-Sampling Initiative (CSi) has shown how human papillomavirus (HPV)-based self-sampling can be used to increase screening participation among 23,632 nonattenders in the Capital Region of Denmark. In this study, we describe HPV prevalence and genotype frequency in 4,824 self-samples as determined by three HPV assays (the CLART, Onclarity, and Hybrid Capture 2 [HC2] assays) and compare the results with those for physician-taken follow-up samples. The HPV self-sample findings were also compared to the findings for a reference population of 3,347 routinely screened women from the Horizon study, which had been undertaken in the same screening laboratory. Nonattenders had an HPV prevalence of 11.3% as determined by the CLART assay, which was lower than that for women from the Horizon study (18.5%). One-third of the CSi women who tested HPV positive by self-sampling tested HPV negative on the physician-taken follow-up sample. The CLART and Onclarity assays agreed on 64% (95% confidence interval [CI], 60 to 68%) of the HPV-positive self-taken samples. When the HC2 assay results were added into a three-way comparison, the level of agreement decreased to 27% (95% CI, 24 to 29%). Our findings suggest that further validation of HPV assays on self-taken samples is needed for optimal HPV detection and correct clinical management of HPV-positive women.

Aim of database: To monitor and improve the quality of the Danish national cervical cancer screening program, an annual report is published, including nine quality indicators.Study population: The screening target group consisted of 1.5 million Danish women aged 23-64 years, but in the calculation of quality indicators, the dataset varies according to indicators being Danish women, cervical cancer cases, or cytology samples.Main variables: The variables include the number of cytology samples per pathology laboratory, participation rate, percentage of unsatisfactory samples, diagnostic sensitivity and specificity, percentage of samples answered within <= 10 days, percentage of atypical squamous cells of undetermined significance samples in women aged >30 years with human papillomavirus-triage, coverage, percentage of non-normal samples not followed up according to recommendations, number of incident cervical cancers, incidence of cervical cancer in the past 5 years, and upcoming percentage of incident cervical cancers undergoing audit.Descriptive data: Annual reports have been published since 2009. Better fulfillment of quality standards has been seen for the size of pathology departments, percentage of unsatisfactory samples, percentage of atypical squamous cells of undetermined significance with human papillomavirus-triage, and a slight decrease in the percentage of non-normal samples not followed up within the recommended time intervals. Stable patterns have been observed for participation rate, coverage, and number of incident cervical cancer cases. With a coverage of 75%, and with presently 16% of non-normal samples not followed up in a timely manner, there is definitely a scope for improvement in the screening program.Conclusion: The database has pinpointed the strengths and weaknesses of the national cervical cancer screening program. Measures to enhance participation rate/coverage and to improve follow-up of non-normal cytology samples are warranted.

High-risk Human Papillomavirus (HPV) testing is replacing cytology in cervical cancer screening as it is more sensitive for preinvasive cervical lesions. However, the bottleneck of HPV testing is the many false positive test results (positive tests without cervical lesions). Here, we evaluated to what extent these can be explained by cross-reactivity, i.e. positive test results without evidence of high-risk HPV genotypes. The patterns of cross-reactivity have been thoroughly studied for hybrid capture II (HC2) but not yet for newer HPV assays although the manufacturers claimed no or limited frequency of cross-reactivity. In this independent study we evaluated the frequency of cross-reactivity for HC2, cobas, and APTIMA assays.

Laboratories now can choose from >100 human papillomavirus (HPV) assays for cervical screening. Our previous analysis based on the data from the Danish Horizon study, however, showed that four widely used assays, Hybrid Capture 2 (HC2), cobas, CLART, and Aptima, frequently do not detect the same HPV infections. Here, we determined the characteristics of the concordant samples (all four assays returning a positive HPV test result) and discordant samples (all other HPV-positive samples) in primary cervical screening at 30 to 65 years of age (n = 2,859) and in a concurrent referral population from the same catchment area (n = 885). HPV testing followed the manufacturers' protocols. Women with abnormal cytology were managed according to the routine recommendations. Cytology-normal/HPV-positive women were invited for repeated testing in 18 months. Screening history and histologically confirmed cervical intraepithelial neoplasia (CIN) in 2.5 years after the baseline testing were determined from the national pathology register. HPV-positive women undergoing primary screening having concordant samples were more likely to harbor high-risk infections and less likely to harbor only low-risk infections than women with discordant samples. Additionally, assay signal strengths were substantially higher in concordant samples. More than 80% of ≥CIN2 results were found for women with concordant samples, and no ≥CIN2 results were found when the infection was detected by only one assay. These patterns were similar in the referral population despite the younger age and higher number of HPV infections. HPV test result discordance identified a cluster of low-risk HPV infections that were hardly ever associated with high-grade CIN and, almost exclusively, represented false-positive screening findings.

In women aged ≥30 years, Human Papillomavirus testing will replace cytology for primary cervical screening. We compared Hybrid Capture 2 (HC2), cobas, CLART, and APTIMA HPV assays with cytology on 2869 SurePath samples from women undergoing routine screening at 30–65 years in Copenhagen, Denmark. Women with cytological abnormalities were managed according to routine recommendations, with 92% completeness. Those with cytology-normal/HPV-positive samples (on any of the four assays) were invited for repeated cytology and HPV testing in 1.5 year, and 58% had additional testing. HPV testing detected more ≥CIN3 than cytology (HC2: 35, cobas, CLART: 37, APTIMA: 34, cytology: 31), although statistically the differences were not significant. Cobas and CLART detected significantly more ≥CIN2 than cytology (cobas, CLART: 49, cytology: 39). The proportion of women with false-positive test results (positive test results without ≥CIN3) varied between 3.3% with cytology and 14.9% with cobas. All HPV assays led to significantly more false-positive tests, whereas compared to HC2 cobas and CLART were associated with a significantly higher and APTIMA with a significantly lower proportion. Detection of CIN1 was particularly increased for the three DNA assays. With APTIMA combined with cytological triage, about 20% more women were referred for colposcopy than with cytology screening. With the three DNA assays, the increase was ≥50%. The number of women with repeated testing was twice as high with APTIMA and almost five times as high with cobas compared to cytology. To our knowledge, Horizon was the only study set in routine practice that compared more than two HPV assays in the same women while also ascertaining the histological status of women with normal cytology/HPV-positive test results. HPV-based screening of Danish women aged 30–65 detected more high-grade CIN but decreased the screening specificity, and increased the demand for additional testing.

We compared the sensitivity and specificity of liquid-based cytology (LBC) and computer-assisted reading for SurePath/FocalPoint and ThinPrep with those of manually read conventional cytology in routine cervical screening in four Danish laboratories. Using data from five nationwide registers, technological phases were identified by slide preparation, reading technique, and triage of borderline cytology. Trends in the detection of cervical intraepithelial neoplasia (CIN) were an indicator of the technology's relative sensitivity, and trends in false-positive tests an indicator of relative specificity. At 23–29 years, SurePath/FocalPoint statistically significantly increased the detection of ⩾CIN3 by 85% compared with manually read conventional cytology. The 11% increase with ThinPrep was not significant. At 30–44 years, the increase with SurePath/FocalPoint was 58%; the 16% increase with ThinPrep was not significant. At 45–59 years, both technologies led to nonsignificant decreases in the detection. SurePath/FocalPoint doubled the frequency of false-positive tests at any age. With ThinPrep, these proportions remained the same at 23–29 years, but decreased by two-thirds at 45–59 years. In a fourth laboratory with continuous use of manually read conventional cytology, no such trends were seen. The sensitivity and specificity of modern LBC and computer-assisted reading technologies may be brand- and age-dependent.

Objective. This study aimed to assess the long-term use of health care services in women with abnormal cytology results compared to women with normal cytology results.Methods. We did a nationwide population-based study, using women aged 23 to 59 years participating in the national organized cervical cancer screening program. We included a study population of 40,153 women with abnormal cytology (exposed) and 752,627 women with normal cytology (non-exposed). We retrieved data from the Danish Civil Registration System, the Danish Pathology Data Bank, the National Health Service, the National Patient and the National Prescription Register. We calculated the frequencies of contacts to general practitioner (GP), to private psychiatrist and/or psychologist, admissions to hospitals and use of prescription drugs. These frequencies were calculated separately in the 5-year period "before" the cytology result and for the 5-year period "after" the result.Results. During the "before" period exposed women had more contacts to GPs, more contacts to psychologists/psychiatrist, and more hospital admissions than non-exposed women. In both exposed and non-exposed women, health care use increased from the "before" to the "after" period. This increase was significantly higher for exposed than non-exposed women regarding contacts to GP, admissions to hospitals, and drug use.Conclusion. Women with abnormal cytology results constitute a selected group with a higher health care use than other women even before they have the abnormal cytology. This difference is further enhanced after the abnormal cytology result. (C) 2015 Elsevier Inc. All rights reserved.

Cervical screening has been one of the most successful public health prevention programmes. For 50 years, cytology formed the basis for screening, and detected cervical intraepithelial lesions (CIN) were treated surgically to prevent progression to cancer. In a high‐risk country as Denmark, screening decreased the incidence of cervical cancer from 34 to 11 per 100 000, age‐standardized rate (World Standard Population). Screening is, however, also expensive; Denmark (population: 5.6 million) undertakes close to half a million tests per year, and has 6–8 CIN‐treated women for each prevented cancer case. The discovery of human papillomavirus (HPV) as the cause of cervical cancer dramatically changed perspectives for disease control. Screening with HPV testing was launched around 1990, and preventive HPV vaccination was licensed in 2006. Long‐term randomized controlled trials (RCT) demonstrated that HPV testing provides better protection against cervical cancer than cytology, but it requires extra repeated testing. HPV vaccination RCTs, furthermore, have proved that HPV vaccination protects against vaccine‐type high‐grade CIN in women vaccinated prior to sexual activity, but less so in women vaccinated later. The challenge now is therefore to find an algorithm for screening of a heterogeneous population including non‐vaccinated women; women vaccinated prior to start of sexual activity; and women vaccinated later.