Histological outcomes in HPV-screened elderly women in Denmark.

INTRODUCTION: Danish women exit cervical cancer screening at age 65 years, but 23% of cervical cancer cases occur beyond this age. In addition, due to gradual implementation of cervical cancer screening, older women are underscreened by today´s standards. A one-time screening with HPV test was therefore offered to Danish women born before 1948. METHODS: Register based study reporting histology diagnoses and conizations in women found HPV positive in the one-time screening. Number and proportion of women with severe or non-severe histology results were calculated for screened and HPV-positive women by age group or region of residence. Number of women with biopsy and/or conization per case of cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) or CIN3+ were also calculated by age groups and region. RESULTS: 4,479 (4.1% of screened women) had positive HPV test. 94% of these had one or more additional tests. 2,785 (62%) of HPV-positive women had histology results, and conization was performed in 1,076 (24% of HPV-positive and 1% of all screened women). HPV positivity and CIN3+ detection varied little between regions, but the proportions of HPV positive women undergoing histology varied between regions from 40% to 86% and the proportion with conization from 13% to 36%. Correspondingly, the number of histologies and conizations per CIN3+ detected varied from 5.9 to 11.2 and 1.8 to 4.7, respectively. In total, 514 CIN2+ (0.47% of screened women, 11% of HPV-positive) and 337 CIN3+ (0.31% of screened women, 7.5% of HPV-positive) were diagnosed, including 37 cervical cancer cases. DISCUSSION: HPV screening of insufficiently screened birth cohorts can potentially prevent morbidity and mortality from cervical cancer but longer follow-up is needed to see if cancer incidence declines in the screened women in the coming years. Management strategies differed among regions which influenced the proportions undergoing biopsy/conization.

Management of low-grade cervical cytology in young women. Cohort study from Denmark.

OBJECTIVE: Cytology findings of atypical squamous cells of unknown significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) are common among women under 30, but evidence on best management strategy is insufficient. We therefore investigated how different management strategies used in Denmark influenced biopsy rates and detection of cervical intraepithelial neoplasia (CIN). METHODS: Register-based cohort study including Danish women aged less than 30 years and born 1980-95, with ASCUS/LSIL as their first abnormal cervical cytology in 2008-16. Rates and relative risks (RR) of biopsy and detection of CIN3+, CIN2 and < CIN2 during two years follow-up were compared between women referred directly to colposcopy after ASCUS/LSIL or undergoing additional testing, including mRNA or DNA test for high risk HPV or repeat cytology. RESULTS: 19,946 women with ASCUS and 19,825 with LSIL were included in the study of whom 92% had adequate information about follow-up. Among women referred directly to biopsy, CIN3+ was detected among 21%, CIN2 in 17%, while 62% had < CIN2. Repeating cytology after 6 months reduced the biopsy rate to 44% of which 53% had < CIN2. Biopsy rates with HPV test were 67% for DNA test, 77% with 14-type mRNA test and 58% with 5-type mRNA test. The detection of CIN3+ was somewhat higher, between 13% and 14% for the three HPV tests vs. 11% with repeat cytology. However, the detection of < CIN2 (not indicating treatment) also increased with RR 2.11 (95% CI 2.01-2.21) for 14-type mRNA test, 1.35 (95% CI 1.29-1.41) for 5-type mRNA test, and 1.86 (95% CI 1.76-1.97) with HPV DNA test. CONCLUSIONS: The choice of management strategy influences both the detection rate for severe lesions (CIN3+) and the proportion of women followed up for potentially insignificant findings.

HPV-prevalence in elderly women in Denmark.

AIM: In countries like Denmark, cervical cancer incidence is at present relatively high in elderly women, while routine screening stops at age 65 years. On this background, all women aged 69 and above were invited to human papillomavirus (HPV)-screening in Denmark in 2017. METHODS: Women were identified from the Central Population Register and personally invited by digital or ordinary mail to have a screening sample taken by their general practitioner. In four regions, samples were tested for high risk (HPV) with the cobas 4800® HPV-assay, and in the last region with the BD Onclarity® HPV-assay. Participation rate, prevalence of high risk HPV, and proportion of positive samples with HPV16, HPV18, and other high risk HPV-types were tabulated by 5-year age-groups. RESULTS: 455,612 women were invited, and 30.2% (95 confidence interval (CI) 30.0-30.3) participated. Average age of participants was 74.6 years. Overall, 4.3% (95% CI 4.1-4.4) of participants were HPV-positive, of whom 24% had HPV 16/18. HPV-prevalence decreased slightly from 4.5% in women aged 69-73 years to 3.1% in women aged 84-88 years, but was 5.2% in the very small group of participants aged 89+ years. CONCLUSION: Invitation to HPV-screening was well received by elderly women. The HPV-prevalence decreased slightly with increasing age. No rebound of HPV-prevalence after menopause was found when our data were combined with previously published Danish data from younger women. The presently relatively high cervical cancer incidence in elderly women was not reflected in the HPV-prevalence.

Cervical screening in Denmark - a success followed by stagnation.

INTRODUCTION: Despite an intensive screening activity, the incidence of cervical cancer in Denmark has remained stable for the last 15 years, 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.

[Screening profile of women who have died from cervical cancer]. / Screeningsprofil af afdøde fynske livmoderhalskraeftpatienter.

INTRODUCTION: Every year about 400 women in Denmark are diagnosed with cervical cancer and more than 175 die from the disease. Studies show that the majority of patients did not participate in screening programmes and that a significant number of non-participants died from the disease compared to participants with two or more previous cervical smears. The aim was to investigate the screening profile of women who died from cervical cancer compared to a control group. MATERIALS AND METHODS: A total of 72 patients were included in a case-control study. Five cases were excluded. One geographical and age-matched control person was drawn by the Danish Civil Registration System. All data files about the disease and screening profile of every case and control person were registered in a data base. The statistics were performed by the chi2-test with Yates correction. RESULTS: 63% of the patients were non-participants compared to 49% of the controls. The study showed that elderly women in particular are insufficiently screened as 65% of cases as well as controls at 60 years or older were non-participants. CONCLUSION: The fact that non-participants suffered from advanced cervical cancers compared to the participants at the time of diagnosis means that increase of the response rate must be the focus of attention in the future.

Automated screening versus manual screening: a comparison of the ThinPrep imaging system and manual screening in a time study.

The ThinPrep Imaging System (TIS) is an automated system that assists cytotechnologists in the primary screening of ThinPrep liquid based cervical samples. Between June 1, 2004, and April 1, 2005, four experienced cytotechnologists participated in the study in which the duration of the screening procedure was timed for each of the 11,354 slides included. In every slide 22 fields of view were reviewed, and the samples that contained potentially abnormal cells were fully screened. The screening time was reduced by 42% (mean) (p < 0.001). By manual rescreening of the negative TIS samples, abnormal cells were found in 10 samples (false negative rate 0.14%). In every case the abnormal cells had been identified by the scanner, but misinterpreted by the cytotechnologist. These findings stressed the importance of carefulness in the interpretation of the marked fields and beyond that helped the cytotechnologists and pathologists to have more confidence in the automated system.

Improvement of diagnostic accuracy and screening conditions with liquid-based cytology.

The aim of this population-based study was to compare the histological follow-up diagnoses of cervicocytological neoplasia (dysplasia, carcinoma in situ and carcinoma) in conventional Papanicolaou (CP) smear and ThinPrep PapTest samples (TP). All cytological samples from the County of Funen, Denmark, in the periods 2000 (n = 34,832) and 2002 (n = 29,995) were included in the study. In 2000 and 2002, the specimens were CP and TP, respectively. The detection rate of > or = mild dysplasia was 0.8% in CP and 1.4% in TP, showing a 75% increase in TP when compared with CP (p < 0.001). Histological follow-up of > or = moderate dysplasia revealed a neoplastic lesion in 77.1% and 87.9% in CP and TP, respectively (P < 0.001). The present study indicates that the diagnostic accuracy of cervical cytology is improved with liquid-based cytology. In addition, we focus on the optimized cellular material that shows the diagnostic details very clearly to the microscopist and leads to radically improved screening conditions.

[False negative Pap smears in a Danish material]. / Falsk negative cervixcytologiske prøver i et dansk materiale.

INTRODUCTION: The aims of screening against cervical cancer are: 1) to reduce the number of cervical cancer cases, 2) to diagnose the cervical carcinoma precursor lesions of which treatment is quite simple and 3) to use the available resources in the best possible way. The purposes of this study were firstly to get an impression of the false negative rate in the County of Funen, secondly to illustrate some of the causes, and thirdly to recommend some ways to reduce the false negative cases in the future. MATERIAL AND METHODS: All previously negative Pap smears in the period from April 1, 1989 to December 31, 1999 from women who had shown at least moderate dysplasia histologically in the period from Jan 1, 1996 to December 31, 2000 were reevaluated. RESULTS: A total of 551 Pap smears were rescreened. Eighty-one per cent were sampling errors and the rest was regarded as interpretation and screening errors. The false negative rate for a single year, 1991, was assessed at 22%. The false negative rate of interpretation and screening errors was 4.6%. DISCUSSION: The results are in accordance with other studies. We describe three characteristical cytological cell patterns as the main causes of the false negative samples. To prevent false negative samples a very important factor is thorough training and further education of the staff. Furthermore, a change into liquid-based cytology will raise the quality both of the cell sample and of the screening procedure.

[Cause and follow-up of inadequate cervical smears in the county of Funen]. / Arsag til og opfølgning af uegnede cervixcytologiske prøver i Fyns Amt.

BACKGROUND: Inadequate cervical smears cause repetition of sampling, which is both costly and a cause of concern to the patient. The objective of this study was to examine why cervical smears were classified as inadequate and to elucidate the underlying diagnoses in order to make recommendations on how to improve smear quality and the interpretation of the sample. MATERIALS AND METHODS: We investigated 2113 inadequate smears from the screening population in the County of Funen and they were classified according to the cause of inadequacy and the final diagnoses. Smears without endocervical cells (ECC) were classified as inadequate. In the study period a total number of 35,628 smears were taken. RESULTS: Most smears were inadequate because of the lack ECC, but inflammatory changes and poor technical quality also contributed. Two cases of cervical cancer and 31 cases of cervical intraepithelial neoplasia were found at follow-up. DISCUSSION: The results indicate that inadequate smears generally conceal benign diagnoses. However, it is still important to reduce the number and to secure follow up, as we found 31 cases of cervical intraepithelial neoplasia and two cervical cancers. Recommendations for obtaining a better smear quality, including the implementation of liquid-based cytology, are given.